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BI-RADS Assessment Categories

ACR BI-RADS 2025 — complete category definitions with management

What Changed: BI-RADS 2025 vs. 5th Edition (2013)

Feature	BI-RADS 5th Ed (2013)	BI-RADS 2025	Clinical Impact
General
Category 0	Single category: "Incomplete — Need Additional Imaging Evaluation and/or Prior Imaging for Comparison"	Split into two: 0A — Need Additional Imaging Evaluation 0B (NEW) — Need Prior Mammograms for Comparison Separated to reflect 2024 FDA MQSA amendments. 0B: must reach final assessment within 30 days.	0B only when priors are genuinely required to render Cat 1 or 2 and can feasibly be obtained. Do NOT use 0A to defer biopsy on a suspicious finding — assign Cat 4/5. Do NOT use 0A/0B to recommend supplemental MRI — give a final category instead.
Category 6	Management: "Surgical excision when clinically appropriate"	Management: "Clinical follow-up with surgeon and/or oncologist, and definitive local therapy (usually surgery) when clinically appropriate." Revised to recognize emerging non-surgical definitive therapies. NEW: Cat 6 may also be used for separate additional close findings (ACFs) within 2cm of biopsy-proven malignancy, if they do not increase total extent >2cm and would not change management.	Ablation and other non-surgical therapies are now acknowledged. The ACF provision for Cat 6 avoids over-classifying small adjacent suspicious findings as Cat 4/5 when they fall within the surgical field.
Report organization	Variable by modality; mammography: 1. Indication 2. Breast composition 3. Findings 4. Comparison 5. Assessment 6. Management	Standardized across all modalities: 1. Indication 2. Comparison to prior exams 3. Technique 4. Breast density/composition 5. Findings 6. Assessment 7. Management recommendations. Structured Exam Indication verbiage standardized.	Technique is now a required report section. Comparison to priors moves up to section 2. Breast density becomes a mandatory standalone section (all modalities).
Mammography
DBT & Synthetic 2D	No more line drawings; all clinical images on digital equipment. DBT addressed but limited examples.	Standard DM, DBT, and synthetic mammogram (SM) examples all included. Mass definition updated: may be apparent on single projection when imaged on DBT (5th ed required 2 views). SM formally recognized: lower spatial resolution than true 2D, can produce pseudocalcifications (artifact not seen on tomo slices).	A mass seen on only one DBT view is valid. For SM: calcifications seen on SM but not tomo slices → likely pseudocalcification artifact. Confirm with true 2D or magnification.
Masses — Margin: Microlobulated	Microlobulated listed as a distinct margin descriptor (intermediate suspicion)	REMOVED as a margin descriptor. A microlobulated margin should now be described as indistinct. Reason: to avoid confusion with the shape term "lobulated."	Do not use "microlobulated margin" — use "indistinct margin" instead. This is one of the most impactful lexicon changes for daily reporting.
Masses — Shape: Lobulated	Masses/shape/lobular eliminated from 5th edition (to prevent confusion with Masses/Margin/Microlobulated)	RETURNED to lexicon as "lobulated" (not "lobular") — term changed to avoid confusion with the lobular subtype of breast cancer. Now valid in mammography, US, MRI, and CEM.	Lobulated shape is back. Use "lobulated" (not "lobular"). Applicable across all modalities for describing gently undulating, rounded mass contours.
Calcification terms removed	Popcorn-like, dystrophic, punctate (as parenthetical subset of round), and milk of calcium listed as distinct types	Popcorn-like → coarse. Dystrophic → coarse. Reason: simplify reporting and move away from food-related descriptors and histopathology-based terms. Punctate parenthetical removed from "round" (both refer to <0.5mm round particles; not practical to distinguish). Milk of calcium → layering (emphasizes morphologic appearance — sedimentation — rather than physiologic make-up).	Use "coarse" for former popcorn/dystrophic. Use "layering" for former milk of calcium (smudgy on CC, layers on lateral view). "Round" now subsumes punctate.
Vascular calcifications	Listed as typically benign	Retained as typically benign; NOW noted to be associated with increased risk of cardiovascular disease per recent literature (referenced). Reporting encouraged when present.	Mention vascular calcifications in the report — they carry clinical significance beyond breast imaging (cardiovascular disease risk marker).
Calcification distribution table	Table 3: Likelihood of Malignancy as Function of BI-RADS Descriptors of Calcification Distribution	REMOVED. Table 3 (calcification morphology PPV) updated with more recent literature. Distribution likelihood table eliminated.	Morphology remains the primary driver for biopsy decision. Distribution (grouped, regional, segmental, etc.) provides context but no longer has its own PPV reference table.
"Developing asymmetry"	Listed as a distinct asymmetry subtype indicating interval change	REMOVED as a descriptor. Delineation of change over time no longer embedded in descriptor terminology. Now described as: an asymmetry (focal or global) that is "enlarging, becoming denser, or more conspicuous."	Do not use "developing asymmetry." Describe the finding type (focal/global asymmetry) and characterize the change in the report narrative.
Lymph nodes	Intramammary lymph node and axillary lymph nodes addressed as separate findings	Combined into a single Lymph Nodes section with sub-findings of intramammary and axillary. Multiple dilated ducts added as a NEW finding — considered typically benign.	Report intramammary and axillary nodes under unified "Lymph Nodes" heading. Multiple dilated ducts ≠ suspicious; solitary dilated duct requires more nuanced assessment (see below).
Solitary dilated duct	Considered suspicious unless benign etiology demonstrated; generally BI-RADS 4A	When not associated with suspicious imaging features (mass, architectural distortion, microcalcifications) and occurring in asymptomatic individuals, can be considered benign. If present on a baseline exam in a symptomatic woman or associated with other suspicious findings → additional imaging evaluation leading to possible tissue diagnosis should be considered.	Asymptomatic, isolated, no associated suspicious features → may be benign. No longer automatically 4A. Symptomatic or associated with suspicious findings → still warrants workup.
Associated features → Secondary findings	Axillary adenopathy, architectural distortion, and calcifications listed as associated features that could stand alone when no other abnormality present	Concept of "secondary findings" introduced: additional abnormalities present in association with a primary finding. Axillary adenopathy → moved to Lymph Nodes section. Architectural distortion → recategorized as a secondary finding. Calcifications → recategorized as a secondary finding.	Architectural distortion and calcifications are no longer "associated features" — they are secondary findings or can be primary findings in their own right.
Depth on MLO view	Determined by imaginary divisions based on vertically oriented lines	Determined by imaginary divisions that parallel the angle of the pectoralis major muscle.	MLO depth stratification (anterior/mid/posterior) now aligns with pec major angle, not vertical lines.
Special cases	Did not include gynecomastia, implants, or mastectomy as mammography special cases	Special cases reintroduced to include Gynecomastia, Implants and other forms of augmentation, and Mastectomy. Hormone-induced breast tissue in transfeminine patients should NOT be characterized as gynecomastia.	Gynecomastia, augmentation, and post-mastectomy imaging now have dedicated guidance in the mammography lexicon.
Ultrasound
Non-mass lesion	Not in previous version	NEW finding introduced: a discrete finding distinctly different from normal tissue, seen in 3 dimensions, but lacking the discrete margination of a mass and unable to be assigned a specific shape. Often subtle; may be detected only because background tissue is disrupted.	Non-mass lesion is now a reportable US finding — analogous to NME on MRI. Report location, size, and associated features.
Tissue composition — GTC	Tissue composition (single descriptor)	Expanded to: Tissue composition/tissue pattern + Tissue composition/glandular tissue component (GTC). GTC defined with supporting evidence.	GTC is a new sub-finding of tissue composition. Report pattern and GTC separately when applicable.
Posterior features — combined pattern	Combined pattern listed as a posterior feature option	Combined pattern removed. If a mass shows any shadowing, it should be characterized as shadowing.	Do not use "combined pattern." If shadowing is present at all → call it shadowing.
Echo pattern	Complex cystic and solid	Mixed solid and cystic (terminology revision)	Use "mixed solid and cystic" — "complex cystic and solid" is retired.
Associated features — new descriptors	Architectural distortion, duct changes, skin changes, edema, vascularity, elasticity assessment	Echogenic pseudocapsule and echogenic rind added as sub-findings to define tissue directly surrounding a finding. Vascularity terminology: "absent" → avascular; "vessels in rim" → peripheral vascularity.	Echogenic pseudocapsule and echogenic rind are new reportable features. Update vascularity terminology accordingly.
Special cases — new entries	Did not include foreign body, abscess, or post-traumatic (non-surgical) changes as explicit special cases	Added: foreign body, implants (as sub-finding), postsurgical changes including fluid collections, fat necrosis, post-traumatic (non-surgical) changes, abscess. Lymph nodes expanded to include intramammary, axillary, internal mammary, and supraclavicular staging.	Abscess and post-traumatic changes are now explicit US special case categories. Lymph node reporting expanded to include internal mammary and supraclavicular nodes.
MRI
Focus	Focus listed as a distinct finding (<5mm enhancing dot)	ELIMINATED as a finding. Focus has been removed from the MRI lexicon entirely.	Do not report "focus" on MRI. Describe small enhancing dots within mass or NME descriptors, or note as too small to characterize. This is a significant change from 5th edition practice.
BPE — minimal	Background parenchymal enhancement: minimal/mild/moderate/marked	BPE/minimal now explicitly includes no enhancement (terminology revision). Four-tier scale retained.	"No enhancement" and "minimal enhancement" are now the same BPE category. Do not create a separate "none" category.
Masses — Margin: Irregular	Masses/Margin/Not circumscribed/Irregular listed as a margin sub-descriptor	"Irregular" replaced by "indistinct" under non-circumscribed margins — to avoid duplication with "irregular" as a shape descriptor, and to harmonize with margin descriptors across other modalities.	Use "indistinct" not "irregular" for non-circumscribed MRI masses. Applies to CEM as well. Harmonizes with the mammography change (microlobulated → indistinct).
T2 signal intensity	Not in previous version as a mass sub-finding	T2 signal intensity added as a mass sub-finding: hyperintense / not hyperintense.	Report T2 signal of masses: hyperintense (e.g., fibroadenoma, cyst, mucinous carcinoma) vs. not hyperintense. Adds important characterization context.
NME — distribution: multiple regions	Non-mass enhancement/distribution/multiple regions listed as a distribution descriptor	REMOVED as a descriptor.	Do not use "multiple regions" as NME distribution. Describe each region separately or use the appropriate distribution term (diffuse, regional, etc.).
Enhancement kinetics	Kinetic curve assessment / initial phase	Kinetic curve assessment → Enhancement kinetics. Initial phase → Early phase (terminology revision).	Use "enhancement kinetics" and "early phase" in reports. "Kinetic curve" and "initial phase" are retired terms.
Internal enhancement — rim	Rim enhancement	Thick rim enhancement (terminology revision — "thick" added for precision)	Use "thick rim enhancement." Plain "rim enhancement" is retired.
Associated features: "invasion" → "involvement"	Skin invasion, nipple invasion, pectoralis muscle invasion, chest wall invasion	"Invasion" changed to "involvement" across all associated features: skin involvement, nipple involvement, pectoralis muscle involvement, chest wall involvement. Peritumoral edema added as a new descriptor. Architectural distortion removed from associated features.	Do not use "invasion" in MRI reports — use "involvement." Peritumoral edema is now a reportable MRI associated feature.
MRI Report organization	1. Indication 2. MRI technique 3. Breast composition 4. Findings 5. Comparison 6. Composite reports 7. Assessment 8. Management	1. Indication 2. Comparison to prior 3. Acquisition parameters 4. Amount of fibroglandular tissue (FGT) 5. Level of BPE 6. Findings 7. Assessment 8. Management recommendations. BPE added as mandatory standalone section.	BPE must be explicitly reported. "Breast composition" → FGT. Acquisition parameters (including abbreviated protocol or DWI use) is now a required section.
Audit & Outcomes
Cancer definition for audit	Tissue diagnosis of DCIS or any type of primary (not metastatic) breast cancer	Updated: tissue diagnosis of DCIS, pleomorphic or florid lobular carcinoma in situ, or any type of primary (not metastatic) invasive breast carcinoma.	PLCIS and FLCIS now count as cancer for audit purposes — important for tracking upgrade rates from high-risk lesions.
Category 3 outcomes in audit	Not included in basic clinically relevant audit	Outcomes for initial BI-RADS Category 3 assessments now included as part of the basic clinically relevant audit (new to v2025).	Track and report Category 3 outcomes (cancer found at follow-up) as part of standard quality metrics — not just Category 4/5.

Source: ACR BI-RADS Atlas 2025

0A Incomplete — Need Additional Imaging

Likelihood of Malignancy: N/A

Use when additional imaging evaluation is needed (spot compression, magnification, ultrasound). Do NOT use Category 0 to recommend MRI for already-suspicious findings — use Category 4 or 5.

Management: Additional imaging evaluation

0B Incomplete — Need Prior Mammograms

Likelihood of Malignancy: N/A

NEW per MQSA amendments effective Sept 10, 2024. Prior mammograms required before final assessment can be rendered.

Management: Retrieve prior exams

1 Negative

Likelihood of Malignancy: Essentially 0%

No mammographic evidence of malignancy. No findings described (differs from Category 2 where a benign finding is explicitly noted).

Management: Routine annual screening

2 Benign

Likelihood of Malignancy: Essentially 0%

Normal assessment with ≥1 described benign finding. Examples: calcified fibroadenoma, lipoma, oil cyst, skin calcification, vascular calcification.

Management: Routine annual screening

3 Probably Benign

Likelihood of Malignancy: >0% but <2%

Short-interval follow-up recommended. NOT recommended if finding has substantially increased or patient has known cancer. Examples: non-calcified circumscribed solid mass, focal asymmetry, cluster of round/punctate calcifications.

Management: 6-month short-interval follow-up

4A Suspicious — Low

Likelihood of Malignancy: >2% to <10%

Low suspicion for malignancy. Examples: palpable partially circumscribed solid mass, new asymmetry.

Management: Tissue sampling (biopsy)

4B Suspicious — Moderate

Likelihood of Malignancy: ≥10% to <50%

Moderate suspicion for malignancy. Examples: indistinct margin mass, grouped amorphous calcifications.

Management: Tissue sampling (biopsy)

4C Suspicious — High

Likelihood of Malignancy: ≥50% to <95%

High suspicion but not classic malignancy appearance. Examples: irregular spiculated mass, fine pleomorphic calcifications.

Management: Tissue sampling (biopsy)

5 Highly Suggestive of Malignancy

Likelihood of Malignancy: ≥95%

Classic appearance of malignancy. Examples: spiculated high-density mass, linear/branching calcifications, spiculated mass + pleomorphic calcifications.

Management: Tissue sampling; initiate workup

6 Known Biopsy-Proven Malignancy

Likelihood of Malignancy: Biopsy-proven

Awaiting definitive therapy. Used for imaging prior to surgical excision or during neoadjuvant therapy monitoring.

Management: Surgical consultation / treatment planning

BI-RADS 2025 Update: Category 0B is new per MQSA amendments (effective Sept 10, 2024). The subcategories 4A/4B/4C are required in mammography reports under MQSA. All incomplete assessments must be resolved to a final category (1–6) after workup.

Breast Density

ACR BI-RADS 2025 — FDA MQSA notification requirements effective Sept 10, 2024

Almost Entirely Fatty

Fibroglandular tissue <25%

Sensitivity of mammography highest. Cancer not likely obscured.

FDA Notification: "Your breast tissue is not dense."

Scattered Fibroglandular Densities

Fibroglandular tissue 25–50%

Some areas may obscure small masses.

FDA Notification: "Your breast tissue is not dense."

Heterogeneously Dense

Fibroglandular tissue 51–75%

May obscure small masses. Supplemental screening may be beneficial.

FDA Notification: "Your breast tissue is dense." (triggers supplemental screening discussion)

Extremely Dense

Fibroglandular tissue >75%

Lowest mammographic sensitivity (~50%). Supplemental screening recommended.

FDA Notification: "Your breast tissue is dense."

MQSA Amendment (Sept 10, 2024): ALL patients must receive written notification of their breast density category in lay language. Dense breasts (C or D) require notification that density may obscure cancers AND that they should discuss supplemental screening with their provider. This is now a federal requirement.

Supplemental Screening Options

Density	Modality	Recommendation	Notes
C/D	Ultrasound	Consider (average risk)	Detects additional 2–4/1000; increased false positives
C/D	MRI	Recommended (high risk ≥20% lifetime)	Most sensitive; requires contrast
C/D	Contrast-Enhanced Mammography (CEM)	Emerging option	Similar sensitivity to MRI; radiation + contrast
D	ABUS (automated US)	Consider	FDA-approved supplemental screening

Screening Recommendations

ACR 2024 guidelines — risk-stratified approach

Average Risk Screening ▾

Age	Recommendation	Notes
<40	No routine screening	Unless risk factors present
40–44	Annual mammography offered (optional)	Patient choice; discuss benefits/risks
45+	Annual screening mammography	ACR/SBI recommend starting at 40
40+	2D vs DBT	DBT preferred; higher CDR, lower recall rate
Any	US supplemental	Consider if dense breasts (C/D) + average risk

ACR and SBI recommend annual mammography starting at age 40 for average-risk women. USPSTF (2024) recommends starting at 40 with biennial screening — ACR disagrees with biennial intervals due to interval cancer risk.

High-Risk Screening (≥20% Lifetime Risk) ▾

Modality	Timing	Indication
Annual screening MRI	Starting age 25–30	BRCA1/2, TP53, PTEN, STK11/CDH1 mutations
Annual mammography	Starting age 30 (or 10 yrs before youngest family dx)	High-risk by Tyrer-Cuzick or other models
Annual MRI + mammo	Alternating every 6 months	BRCA carriers per NCCN
Clinical breast exam	Every 6–12 months	All high-risk patients

High-risk criteria: BRCA1/2 mutation carrier or 1st-degree untested relative; TP53/PTEN/STK11/CDH1 mutation; ≥20% lifetime risk by risk model; history of chest RT between age 10–30; Li-Fraumeni/Cowden/Bannayan-Riley-Ruvalcaba syndrome.

Intermediate Risk (15–20% Lifetime) ▾

Modality	Recommendation
Annual mammography	Standard
Consider MRI supplemental	Individualized; discuss with patient
Annual clinical breast exam	Recommended

Personal history of breast cancer, ADH, ALH, LCIS → increased surveillance; discuss with managing physician.

Mammography — Masses

ACR BI-RADS 5th Ed. mammography lexicon

Shape ▾

Term	Description	Suspicion
RoundRA	Spherical; equal dimensions	Low (if circumscribed)
OvalRA	Elliptical; may have 2–3 undulations	Low (if circumscribed)
IrregularRA	Neither round nor oval	HIGH

Margin ▾

Term	Description	Suspicion
CircumscribedRA	Well-defined; sharp transition	Benign — requires ≥75% circumscribed
Obscured	Hidden by superimposed tissue; ≥25% obscured	Indeterminate — needs additional views
MicrolobulatedRA	Short-cycle undulations	Intermediate
IndistinctRA	No clear demarcation from surrounding tissue	Suspicious
SpiculatedRA	Lines radiating from mass	Highly Suspicious

A mass must be seen in 2 projections to be called a mass (vs. asymmetry). Partially obscured circumscribed masses that are new/growing should be upgraded.

Density ▾

Term	HU Equivalent	Notes
High density	Denser than equal volume of fibroglandular tissue	Suspicious — possible malignancy
Equal density	Same as fibroglandular tissue	Indeterminate
Low density	Less dense than equal volume of tissue	Typically benign (lipid-containing)
Fat-containing	Contains fat (lucent areas)	Benign — lipoma, oil cyst, hamartoma, LN

Mammography — Calcifications

Morphology and distribution — the most important section in mammography BI-RADS

Morphology (Descriptors) ▾

Term	Assessment
Typically Benign
Skin (dermal)	Lucent center; confirm with tangential view	BI-RADS 2
Vascular	Parallel tracks or tram-tracks along vessels	BI-RADS 2
Coarse/popcorn	Involuting fibroadenoma; >1mm, dense	BI-RADS 2
Large rod-like	Plasma cell mastitis; >1mm rods, may branch	BI-RADS 2
Round	≥1mm spheres, uniform	BI-RADS 2 or 3
Lucent-centered	Round/oval with lucent center	BI-RADS 2
Eggshell/rim	Thin calcification on sphere surface (oil cyst)	BI-RADS 2
Milk of calcium	Tea-cup on lateral; smudgy on CC	BI-RADS 2
Dystrophic	Irregular, >0.5mm; post-trauma/radiation	BI-RADS 2
Suture	Tubular/linear; post-radiation	BI-RADS 2
Intermediate Concern
AmorphousRA	Indistinct, cloudlike; too small to characterize	BI-RADS 4B
Coarse heterogeneousRA	Irregular, >0.5mm but not benign morphology	BI-RADS 4A–4B
Higher Suspicion
Fine pleomorphicRA	Irregular, <0.5mm, varied shapes	BI-RADS 4B–4C
Fine linear/branchingRA	Thin irregular lines; filling ductal lumen	BI-RADS 4C–5

Fine linear/branching (casting) calcifications have the highest PPV for DCIS (~70%). Amorphous calcifications have PPV ~20%.

Distribution ▾

Term	Definition	Significance
DiffuseRA	Random throughout breast	Typically benign (bilateral)
RegionalRA	Large portion of breast tissue (not ductal)	May be benign or suspicious
Grouped (clustered)RA	≥5 calcifications in <2cm	Suspicious if morphology suspicious
LinearRA	In a line (may branch); suggests ductal	Suspicious
SegmentalRA	Wedge-shaped; ductal/lobular distribution	Highly Suspicious

Segmental distribution with fine pleomorphic/linear morphology = BI-RADS 4C–5. Always report morphology AND distribution.

Mammography — Architectural Distortion

Spiculation without a definite mass center

Architectural distortion is spiculation of the parenchyma radiating from a point without a visible central mass. It is one of the most commonly missed mammographic findings. On DBT, it is significantly more conspicuous.

Cause	Features	Management
Radial scar/CSL	Mimics cancer; central lucency on 2D; may be invisible on one view	Biopsy (upgrade rate 0–8%)
Post-surgical scar	History of surgery; stable over time	Compare to prior; stable = BI-RADS 2
Invasive carcinoma	New, increasing, associated mass/calcs	BI-RADS 4–5; biopsy
Sclerosing adenosis	May appear as distortion	Biopsy to exclude malignancy
Fat necrosis	Post-trauma/biopsy history; may have oil cyst	Clinical correlation

ACR 2025: Architectural distortion that is new, has no surgical history, or is associated with calcifications should be assigned BI-RADS 4–5. DBT improves detection by ~40% over 2D mammography for architectural distortion.

Asymmetries & Associated Features

Asymmetric findings and secondary signs of malignancy

Asymmetry Types ▾

Type	Definition	Assessment
Asymmetry	Seen on one view only	Likely summation; needs confirmation
Global asymmetry	Occupies ≥1 quadrant; no mass, distortion, or calcs	Usually benign if stable; new = BI-RADS 0/3
Focal asymmetry	<1 quadrant; seen on 2 views; no central mass	New/growing = BI-RADS 4; stable = BI-RADS 3
Developing asymmetry	New or enlarging focal asymmetry vs. prior	BI-RADS 4 — high PPV (~15%)

Developing asymmetry has PPV of ~12–15% — biopsy recommended (BI-RADS 4A minimum).

Associated Features (Secondary Signs) ▾

Feature	Significance
Skin retraction	Suspicious — Cooper's ligament involvement
Nipple retraction	Suspicious if new
Skin thickening	Inflammatory cancer vs. benign skin change
Trabecular thickening	Lymphedema, inflammatory cancer, or benign
Axillary adenopathy	Suspicious if enlarged/dense — biopsy indicated
Architectural distortion	Secondary sign when associated with mass
Skin lesion	Mark with BBs if applicable

Special Cases — Mammography

Specific entities with established imaging features

Entity	Features	BI-RADS	Notes
Simple cyst	Round/oval; circumscribed; may resolve	2	Confirm with US
Clustered microcysts	≤3mm anechoic spaces; thin septa	2	If purely simple on US
Complicated cyst	Homogeneous low-level echoes	3	6-mo follow-up if single
Skin lesion	With BB marker; identifiable as skin	2	Use tangential view
Intramammary lymph node	Reniform; fatty hilum; ≤1cm; upper-outer quadrant	2	Classic location and morphology required
Hamartoma (fibroadenolipoma)	Mixed density; pseudocapsule; "breast within breast"	2	Pathognomonic appearance
Vascular calcifications	Tram-track pattern along vessels	2	Calcified vessel walls
Fat necrosis	Oil cyst, dystrophic calcs, lipid-filled mass	2	History of trauma/surgery
Diabetic mastopathy	Ill-defined dense mass; US shows posterior shadowing	3–4	Needs biopsy
Mondor disease	Thrombophlebitis of superficial vein	2	Clinical and US diagnosis

Digital Breast Tomosynthesis (DBT)

3D mammography — technical considerations and clinical applications

DBT vs 2D Comparison

Parameter	2D FFDM	DBT
Cancer detection rate	Baseline	+1–2.5/1000 improvement
Recall rate	Baseline	Reduces by 15–40%
Architectural distortion detection	Limited	Significantly improved
Calcification evaluation	Standard	May need 2D for calcification morphology
Radiation dose	1×	~2× (DBT + synthetic 2D); similar if C-View used
Insurance coverage	Standard	Now widely covered

Synthetic 2D (C-View / Insight 2D)

Reconstructed 2D from DBT data eliminates need for acquired 2D. Comparable sensitivity to FFDM. Reduces total dose to ~1.25× FFDM. Standard of practice in most centers.

DBT-Specific Findings

Architectural distortion: much more conspicuous on DBT; responsible for most incremental cancers detected
Masses: better margin characterization; reduced superimposition
Calcifications: BI-RADS 2025 recommends reviewing calcifications on both DBT and 2D (synthetic); fine morphology better on acquired 2D
Asymmetries: many 2D asymmetries resolve (summation artifact) on DBT

ACR BI-RADS 2025: DBT is now the preferred modality for screening and diagnostic mammography where available. Synthetic 2D is an acceptable replacement for acquired 2D.

Ultrasound — Mass Characteristics

ACR BI-RADS US lexicon

Shape & Orientation ▾

Term	Description	Suspicion
RoundRA	Spherical	Low if circumscribed
OvalRA	Elliptical; up to 3 gentle lobulations	Low
IrregularRA	Neither round nor oval	Suspicious
Parallel (wider-than-tall)RA	Long axis parallel to skin	Benign orientation
Not parallel (taller-than-wide)RA	AP dimension > transverse	Suspicious — violates tissue planes

Margin ▾

Term	Notes	Suspicion
CircumscribedRA	Abrupt transition; no angular margin	Benign
Not circumscribed	Any of: indistinct, angular, microlobulated, spiculated	Suspicious
IndistinctRA	No clear edge	Suspicious
AngularRA	Sharp angles; infiltrating growth	Suspicious
MicrolobulatedRA	Short-cycle undulations	Intermediate
SpiculatedRA	Radiating lines	Highly Suspicious

Echo Pattern ▾

Term	Appearance	Association
Anechoic	No internal echoes	Simple cyst (BI-RADS 2)
Hyperechoic	Echogenicity > fat	Usually benign (lipoma, fat lobule)
Complex cystic & solid	Mixed solid/cystic	Biopsy if symptomatic or new
HypoechoicRA	Less echogenic than fat	Variable — needs full characterization
Isoechoic	Same as fat	Variable
Heterogeneous	Mixed echo pattern	Indeterminate

Posterior Features & Associated Features ▾

Term	Significance
No posterior features	Indeterminate
Enhancement (posterior acoustic enhancement)	Benign — fluid-filled structure
ShadowingRA	Suspicious — fibrous or malignant tissue
Combined pattern	Indeterminate
Calcifications in mass	Highly suspicious if coarse
Architectural distortion	Suspicious
Duct changes	Suspicious
Skin changes	Thickening/retraction = suspicious
Edema	Inflammatory process
Vascularity	Internal vascularity increases suspicion

Ultrasound — Cysts & Special Cases

Classification and management

Type	US Features	BI-RADS	Management
Simple cyst	Anechoic; circumscribed; posterior enhancement; no internal echoes; thin wall	2	Routine screening; no follow-up needed
Clustered microcysts	Multiple ≤3mm anechoic spaces; thin (<0.5mm) septa; no solid component	2	Routine follow-up
Complicated cyst	Homogeneous low-level internal echoes; circumscribed; no thick wall/solid component	3	6-month follow-up if single; if multiple = BI-RADS 2
Complex cystic & solid	Thick wall (>0.5mm), thick septation, intracystic solid mass, or mixed solid/cystic	4	Biopsy
Abscess	Thick irregular wall; internal debris; tender; clinical fever	—	Clinical management; aspiration
Galactocele	Complex cyst in lactating/post-lactating woman	2–3	Clinical
Oil cyst (fat necrosis)	Circumscribed; anechoic to complex; post-trauma history	2	No follow-up if classic
Sebaceous/epidermal inclusion cyst	Skin origin; posterior shadowing	2	No action if classic

The ACR BI-RADS update clarifies: A single uncomplicated complicated cyst = BI-RADS 3. Multiple similar complicated cysts = BI-RADS 2. Any solid component, thick wall, or thick septation → BI-RADS 4.

Ultrasound — Lymph Nodes

Axillary, intramammary, and regional assessment

Feature	Normal	Abnormal/Suspicious
Shape	Reniform (kidney-shaped)	Round
Hilum	Echogenic fatty hilum present	Absent fatty hilum
Cortex	≤3mm uniform cortical thickness	Focal cortical thickening >3mm
Size	Variable; cortex thickness more important than size	Entire node >2cm without fatty hilum
Vascularity	Hilar flow pattern	Peripheral/internal vascularity
Number	Multiple normal-appearing	Single enlarged abnormal node

Management

Finding	Action
Normal axillary LN	BI-RADS 1/2 — no action
Abnormal (focal cortical thickening)	BI-RADS 4 — consider biopsy (FNA or CNB)
Intramammary LN	BI-RADS 2 if classic reniform with fatty hilum in upper outer breast
Metastatic workup	Staging CT or PET-CT if biopsy-proven axillary mets

ACR BI-RADS 2025: Cortical thickness >3mm focal thickening is the most reliable criterion for abnormal axillary lymph node, more reliable than size alone.

Vascularity & Elastography

Doppler and strain/shear-wave assessment

Vascularity (Color/Power Doppler) ▾

Finding	Interpretation	Action
Absent vascularity	Simple cyst; or avascular solid mass	Not independently suspicious
Internal vascularity	More common in malignancy	Increases suspicion
Peripheral vascularity	Circumferential rim vessels	More common in benign lesions
Increased hilar flow	Normal LN	Reassuring
Absent hilar flow	Metastatic LN	Suspicious

Vascularity alone does not determine BI-RADS category but should be documented. Taller-than-wide + internal vascularity significantly increases malignancy probability.

Elastography (Strain / SWE) ▾

Technique	Principle	Malignancy Feature
Strain elastography	Compression; relative stiffness	Stiff (blue in standard colormap) = suspicious
Shear-wave elastography (SWE)	Acoustic push; quantitative kPa	>80 kPa highly suspicious; <30 kPa reassuring

Clinical use: Elastography is an adjunct — not a replacement for greyscale + Doppler assessment. Most useful for BI-RADS 3 and 4A lesions where stiffness may help guide biopsy vs. follow-up decision. Not required per ACR BI-RADS but increasingly standard.

MRI — Background Parenchymal Enhancement

BPE assessment and clinical relevance

Minimal

<25% fibroglandular tissue enhancing

Optimal exam; highest conspicuity for enhancement.

Mild

25–50% enhancing

Generally adequate for interpretation.

Moderate

51–75% enhancing

May limit lesion detection; consider timing (days 7–14 of cycle).

Marked

>75% enhancing

Significantly limits interpretation; consider repeating in follicular phase (days 7–14).

Symmetry

Type	Pattern	Interpretation
Symmetric BPE	Bilateral, similar distribution	Expected finding — document, continue interpretation
Asymmetric BPE	Unilateral or focal	Warrants attention — consider pathologic enhancement

Clinical Factors

Factor	Effect on BPE	Action
Premenopausal	Higher BPE (luteal phase)	Schedule days 7–14 of cycle
Postmenopausal	Lower BPE (no HRT)	Optimal timing
HRT use	Elevated BPE	Document; may limit sensitivity
Tamoxifen/AIs	Reduce BPE	Associated with treatment response
Post-RT (treated breast)	Reduced/absent BPE	Expected; compare with contralateral

ACR BI-RADS MRI: BPE is documented for both breasts separately. Asymmetric BPE or focally increased BPE is a reportable finding. Moderate/marked BPE → consider repeating in follicular phase if diagnosis is uncertain.

MRI — Masses & Enhancement Kinetics

Morphology, internal enhancement pattern, and kinetic curve analysis

Mass Morphology ▾

Shape

Shape	Description	Suspicion
Round	Spherical	Lower suspicion
Oval	Elliptical; ≤3 undulations	Lower suspicion
Irregular	Neither round nor oval	Suspicious

Margin

Margin	Interpretation
Circumscribed	Benign-leaning — sharp, well-defined
Irregular	Suspicious — uneven, jagged
Spiculated	Highly Suspicious — radiating projections

Internal Enhancement Pattern ▾

Pattern	Description	PPV for Malignancy
Homogeneous	Uniform; confluent	Lower (~15–20%)
Heterogeneous	Non-uniform	Intermediate
Rim enhancementRA	Peripheral > central	Higher (~40–50%)
Dark internal septations	Low-signal septa within enhancing mass	Benign (fibroadenoma feature)
Enhancing internal septations	Enhancing septae	More suspicious
Central enhancement	Center more than periphery	Variable

Enhancement Kinetics ▾

Initial Phase (1–2 min post-contrast)

Slow (<50% signal increase) — Benign/indeterminate
Medium (50–100% increase) — Indeterminate
Rapid (>100% increase) — Suspicious

Type I — Persistent

Signal continues to rise. Benign pattern. PPV ~6%

Type II — Plateau

Signal stabilizes. Indeterminate. PPV ~25%

Type III — Washout

Signal decreases after peak. Suspicious. PPV ~60–70%

Kinetics are adjuncts to morphology — morphology takes precedence in assessment. A washout curve in a circumscribed homogeneous mass (fibroadenoma) does not mandate biopsy if morphology is classic. A persistent curve in an irregular spiculated mass does not exclude malignancy.

MRI — Non-Mass Enhancement (NME)

Enhancement without a discrete 3D mass — the most important MRI section

NME Distribution (most important factor) ▾

Distribution	Definition	Suspicion Level
FocalRA	<25% of a quadrant; may be single focus	Low–Intermediate
LinearRA	In a line; may branch; suggests ductal	Suspicious
SegmentalRA	Wedge-shaped; apex toward nipple; ductal/lobular unit	Highly Suspicious — PPV ~65–75%
RegionalRA	Large area; not ductal distribution; ≥25% of quadrant	Intermediate
Multiple regions	≥2 regions separated by fat	Usually benign (bilateral BPE) or multifocal DCIS
Diffuse	Throughout most of breast	Usually BPE or treatment effect

NME Internal Pattern ▾

Pattern	Description	Suspicion
Homogeneous	Uniform enhancement	Lowest suspicion (may be BPE)
Heterogeneous	Variable enhancement	Intermediate
ClumpedRA	Cobblestone/confluent foci in non-mass area	Suspicious — PPV ~45%
Clustered ringRA	Ring-enhancing foci clustered together	Highest Suspicion — PPV ~60–79%

NME assessment combines distribution + internal pattern. The most suspicious combination is SEGMENTAL distribution + CLUMPED or CLUSTERED RING pattern → BI-RADS 4C–5. Segmental NME is the hallmark of DCIS on MRI.

Key Clinical Scenarios

Scenario	Interpretation / Action
Segmental NME + clumped	DCIS until proven otherwise → BI-RADS 4C–5
Linear NME	Consider DCIS → BI-RADS 4B–4C; biopsy
Regional homogeneous NME bilateral	BPE → BI-RADS 1–2
Focal NME new	BI-RADS 3–4A; consider 6-month follow-up vs. biopsy

MRI — Associated Features & Clinical Scenarios

Secondary signs, implant assessment, and high-risk indications

Associated Features ▾

Feature	Significance
Nipple retraction	New: suspicious; correlate with clinical exam
Skin thickening	>3mm; inflammatory carcinoma vs. benign skin change
Skin enhancement	Direct dermal involvement — T4d staging
Pectoralis muscle invasion	T4a staging; contact is not invasion
Chest wall invasion	Requires muscle/rib involvement
Axillary adenopathy	Abnormal morphology: round, no hilum, cortex >3mm
Peri-tumoral edema	Common in IDC; not independently suspicious
Satellite lesions	Additional foci near index cancer — affects surgical planning
Duct extension	Ductal carcinoma pathway toward nipple

Implant Assessment (ACR BI-RADS) ▾

Finding	Implant Type	Significance
Intracapsular rupture	Silicone	Linguini sign (collapsed shell); keyhole sign
Extracapsular rupture	Silicone	Free silicone outside capsule; snowstorm on US
Gel bleed	Silicone	Normal finding; subclinical silicone permeation
Capsular contracture	Any	Clinical; Baker grade I–IV
Normal saline implant	Saline	Valve or fold artifact; no rupture assessment needed

MRI with implant protocol (WIRI without and with fat sat, plus silicone-specific sequences) is the gold standard for implant integrity assessment.

High-Risk Screening MRI Indications ▾

BRCA1/2 mutation carrier or untested first-degree relative of carrier
Lifetime risk ≥20% by Tyrer-Cuzick or other validated model
History of chest/mediastinal RT between ages 10–30
Li-Fraumeni, Cowden, Bannayan-Riley-Ruvalcaba syndrome
TP53, PTEN, STK11, or CDH1 pathogenic variant
Personal history of breast cancer + dense breasts OR diagnosed ≤50 (individualized)

Intermediate-risk (15–20% lifetime): MRI benefit is debatable; shared decision-making recommended. Discuss with ordering provider. Dense breasts alone (without other risk factors) does NOT meet ACR criteria for screening MRI.

Reporting — Required Elements

MQSA-compliant breast imaging report structure

Mammography Report — Required Elements (MQSA) ▾

Element	Requirement
Patient information	Name, DOB, date of exam
Indication	Screening vs. diagnostic; clinical history
Breast composition	Breast density category A–D (lay language required)
Findings	Description using ACR BI-RADS lexicon
Comparison	Prior study date and findings if available
Impression	Final BI-RADS category (0A, 0B, 1, 2, 3, 4A, 4B, 4C, 5, 6)
Recommendation	Specific management recommendation matching category
Dense breast notification	Required for C/D; lay language; per MQSA 2024
Radiologist signature	Required; interpreting physician credentials

Diagnostic Mammography vs. Screening ▾

Parameter	Screening	Diagnostic
Indication	Asymptomatic; routine	Symptom, palpable finding, abnormal screening, high-risk
Immediate read	Not required (batch reading)	Real-time read required
Additional views	Not performed at time of exam	May be performed during exam
Category 0	Acceptable	Avoid — resolve to final category
Radiologist on-site	Not required	Required (per most protocols)

Concordance Principles ▾

Imaging-pathology concordance must be assessed for all biopsy results
Concordant benign: imaging features match benign pathology → routine follow-up
Concordant malignant: imaging features match malignancy → proceed with treatment
Discordant: pathology does not explain imaging findings → repeat biopsy or excision
Upgrade at excision: CNB shows high-risk lesion (ADH, ALH, LCIS, radial scar, papilloma) and excision shows carcinoma

Audit & Quality Metrics

ACR BI-RADS 2025 — outcome monitoring and benchmarking

Medical Audit Definitions ▾

Metric	Definition	ACR Benchmark
Recall rate (screening)	% of screening exams recalled for additional imaging	5–12% (avg ~10%)
Cancer detection rate (CDR)	Cancers detected per 1,000 screening exams	≥2.5/1,000 (avg ~5/1,000 with DBT)
PPV1 (abnormal interpretation)	Cancer found / all recalled exams	3–8% (avg ~5%)
PPV2 (biopsy recommended)	Cancer found / all biopsy recommendations	20–40% (avg ~25–35%)
PPV3 (biopsy performed)	Cancer found / all biopsies performed	25–40%
Sensitivity	True positives / (true positives + false negatives)	≥75% (goal ~85%)
Specificity	True negatives / (true negatives + false positives)	≥88%
Stage distribution	% cancers detected at Stage 0/I	Goal >50% Stage 0/I

Minimum Required Data for Audit ▾

All BI-RADS assessments must be tracked
Mandatory linkage of outcomes (cancer yes/no) to imaging interpretation
Annual audit report required by ACR accreditation
Benchmark comparison against national norms

Interval Cancer Rate ▾

Definition: Cancer diagnosed within 12 months of a negative or benign screening exam
Target: <2 per 1,000 negative screens
High interval cancer rate suggests: increased breast density, rapidly growing tumors, or interpretation errors
DBT reduces interval cancer rate by ~15–25% compared to 2D mammography

ACR recommends every breast imaging practice maintain a prospective outcomes database. Failure to meet benchmarks (recall >14% or CDR <2.5/1000) requires quality review.

Mammography — Lymph Nodes

Intramammary and axillary lymph node assessment on mammography

Intramammary Lymph Nodes

Normal finding when classic morphology present

▾

Feature	Normal	Abnormal
Shape	Reniform (kidney-shaped)	Round, loss of normal contour
Fatty hilum	Present — echogenic/lucent center	Absent SUSPICIOUS
Size	Typically <1 cm; variable	>2 cm without fatty hilum
Location	Upper outer quadrant, along vessels	Any quadrant — raises suspicion
Number	Solitary or few	Multiple enlarged nodes
Cortex	Thin, uniform	Focal cortical thickening >3 mm SUSPICIOUS

BI-RADS 2025: Intramammary lymph node with classic features (reniform, fatty hilum, upper outer quadrant) = BI-RADS 2. A lymph node that has lost its fatty hilum, is round, or has cortical thickening should be assigned BI-RADS 4 and considered for biopsy.

Axillary Lymph Nodes on Mammography

▾

Finding	Assessment	Action
Normal morphology	BI-RADS 1/2	Routine
Enlarged, maintains fatty hilum	BI-RADS 2–3	Correlate clinically
Dense/replaced hilum	BI-RADS 4 SUSPICIOUS	Ultrasound ± biopsy
Multiple dense nodes, bilateral	Consider systemic cause	Clinical correlation (lymphoma, reactive, sarcoid)
Unilateral dense nodes with known ipsilateral cancer	Staging N1	FNA or CNB for staging

Skin Lesions & Dilated Ducts

Cutaneous findings and ductal pathology on mammography

Skin Lesions

▾

Entity	Features	BI-RADS	Workup
Sebaceous/epidermal cyst	Round/oval; may have lucent center; skin surface origin	2	Tangential view to confirm skin origin
Neurofibromatosis lesion	Multiple skin nodules projecting over breast	2	Clinical history; mark with BB
Scar	Architectural distortion at prior surgery site; stable	2	Compare to prior; stable = benign
Skin thickening (diffuse)	>3 mm; unilateral or bilateral	0–4	Unilateral new: consider inflammatory CA; bilateral: CHF, lymphedema
Skin retraction/dimpling	Puckering at skin surface	4–5 SUSPICIOUS	Workup for underlying malignancy
Nipple retraction (new)	Inverted nipple, new	4 SUSPICIOUS	US of subareolar region; biopsy if mass found
Paget disease	Nipple/areola skin changes; associated DCIS	4–5	Skin punch biopsy; MRI for extent

Tip: Always use radiopaque markers (BBs) on palpable skin lesions and scars to distinguish cutaneous from intramammary findings on mammography.

Dilated Ducts (Ductal Ectasia)

▾

Finding	Description	BI-RADS	Notes
Simple ductal ectasia	Tubular subareolar lucency or density; bilateral; rod-like calcifications	2	Benign — plasma cell mastitis pattern
Unilateral duct dilation	Single dilated duct; new or symptomatic	0–3	US to evaluate for intraductal mass
Duct with intraductal mass	Filling defect in dilated duct	4 SUSPICIOUS	Galactography or MRI; biopsy
Bloody nipple discharge + duct dilation	High clinical concern	4 SUSPICIOUS	US, galactography, or MRI; surgical consult

ACR guidance: Unilateral spontaneous nipple discharge (especially bloody or clear, from single duct) warrants imaging workup with targeted US ± galactography or breast MRI, regardless of mammographic findings.

Ultrasound — Tissue Composition

Background echotexture and its effect on lesion conspicuity

Background Echotexture

Reported at the beginning of each US report

▾

Type	Description	Clinical Relevance
Homogeneous — fat	Uniformly echogenic; fatty tissue predominates	Excellent conspicuity; lesions easy to detect FAVORABLE
Homogeneous — fibroglandular	Uniformly echogenic with fibroglandular tissue	Good conspicuity for hypoechoic masses
Heterogeneous	Mixed echogenicity; uneven background	Reduced conspicuity; may obscure small lesions LIMIT

Lesion Visibility & Reporting

▾

Consideration	Details
Echogenicity reference	Subcutaneous fat is the standard reference for echogenicity comparisons
Skin thickness	Normal: 0.5–2 mm; >3 mm = skin thickening (reportable)
Cooper's ligaments	Thin echogenic lines; thickening/distortion = associated feature of malignancy
Chest wall layers	Ribs (acoustic shadow), intercostal muscles, pleura visible — evaluate for chest wall involvement

BI-RADS 2025: Tissue composition (echotexture) should be documented in breast US reports to provide context for lesion detection and potential limitations.

Ultrasound — Non-Mass Lesions

Findings that do not qualify as discrete masses

Non-Mass Lesion Descriptors

▾

Finding	Description	BI-RADS	Notes
Focal echotexture change	Area of altered echogenicity without discrete mass; no posterior features	3–4	New or symptomatic = biopsy; stable = follow-up
Architectural distortion	Distortion of normal tissue planes; radiating lines; no central mass	4 SUSPICIOUS	Correlate with mammography; biopsy
Ductal changes	Dilated or abnormal-appearing ducts (intraductal solid component)	4 SUSPICIOUS	Evaluate with Doppler; galactography or MRI
Skin thickening	Diffuse or focal skin >3 mm	Variable	Unilateral new: rule out inflammatory carcinoma
Edema	Increased echogenicity of fat; skin thickening; Lymphedematous change	Variable	Infection vs. malignancy vs. systemic cause
Pre-pectoral collection	Fluid anterior to pectoralis; post-procedure	Variable	Hematoma vs. seroma vs. abscess

Duct Evaluation

▾

Finding	Significance	Action
Normal duct	<2 mm; anechoic; subareolar; collapses with pressure	BI-RADS 1/2
Dilated duct ≥3 mm	Duct ectasia; alone = may be benign	Evaluate for intraductal mass
Intraductal solid mass	Papilloma, DCIS, or invasive cancer SUSPICIOUS	BI-RADS 4; biopsy
Branching duct with solid component	Highly suspicious for DCIS/papillary carcinoma SUSPICIOUS	BI-RADS 4C–5; biopsy + MRI

Ultrasound — Calcifications

US detection and characterization of breast calcifications

Note: Mammography remains the gold standard for calcification detection and characterization. US calcifications are an associated finding, not the primary means of assessment.

Calcification Descriptors on US

▾

Type	US Appearance	Significance
Macrocalcifications	Echogenic foci with posterior acoustic shadowing; >0.5 mm	Usually benign (fibroadenoma, vessel); correlate with mammography
Microcalcifications in mass	Punctate echogenic foci within solid mass; may shadow	Increases suspicion for malignancy SUSPICIOUS
Clustered microcalcifications	Group of punctate echogenic foci; may correspond to grouped mammo calcs	BI-RADS 4 if no mass; biopsy if no mammographic correlation
Calcifications in cyst wall	Echogenic rim; posterior shadow	Benign (dystrophic) if classic circumscribed cyst BENIGN
Milk of calcium	Echogenic layer with posterior shadowing; moves with position change	BI-RADS 2 — benign BENIGN
Calcifications in DCIS area	Ill-defined echogenic region ± calcifications; no discrete mass	BI-RADS 4; MRI or biopsy guided by mammography findings

Correlation with Mammography

▾

Scenario	Approach
Mammo calcifications with no US correlate	Stereotactic biopsy if suspicious morphology (not US-guided)
Mammo calcifications + US mass	US-guided biopsy with calcium confirmation (specimen radiograph)
US calcifications + normal mammogram	Reassign based on mammographic morphology; avoid overdiagnosis
Post-biopsy clip calcification	BI-RADS 2 — benign procedure change

Specimen radiograph: Always obtain specimen radiograph after US-guided biopsy targeting calcifications to confirm adequate sampling.

Ultrasound — Associated Features

Secondary findings that modify the assessment of the primary lesion

Associated Features Lexicon

▾

Feature	Description	Significance
Architectural distortion	Disruption of normal tissue planes adjacent to lesion	Highly suspicious SUSPICIOUS
Duct changes	Dilated ducts leading to or from a mass	Raises suspicion for ductal carcinoma SUSPICIOUS
Skin thickening	Skin >3 mm overlying lesion; local or diffuse	Suspicious if focal and adjacent to lesion SUSPICIOUS
Skin retraction	Puckering or dimpling of skin surface	Suspicious — ligamentous involvement SUSPICIOUS
Edema	Increased echogenicity of surrounding fat; fluid in tissue planes	Inflammatory process; may indicate malignancy
Vascularity	Internal or peripheral blood flow on Doppler	Internal vascularity in solid mass increases suspicion
Elasticity assessment	Tissue stiffness (qualitative or quantitative)	Stiff mass = more suspicious; soft = less suspicious
Calcifications in mass	Echogenic foci within the lesion	Increases suspicion if fine; may be benign if coarse SUSPICIOUS
Lymph nodes	Regional nodal assessment (axillary, intramammary)	Abnormal morphology → staging implications

BI-RADS 2025: Associated features should be documented separately from the primary lesion descriptors. They can upgrade or support a given BI-RADS assessment but do not independently determine the category.

MRI — Lymph Nodes

Axillary, internal mammary, and intramammary nodal assessment

Axillary Lymph Node Assessment (MRI)

▾

Feature	Normal	Suspicious
Shape	Reniform	Round SUSPICIOUS
Fatty hilum	Present; T1 bright central hilum	Absent SUSPICIOUS
Cortical thickness	<3 mm, uniform	Focal or diffuse >3 mm SUSPICIOUS
Enhancement pattern	Rim or hilar pattern	Heterogeneous, diffuse SUSPICIOUS
Size	Variable; rely on morphology	Replacement of fatty hilum at any size

Internal Mammary Lymph Nodes

▾

Finding	Notes
Normal internal mammary LN	Small (<5 mm), smooth, along internal mammary vessels; BI-RADS 1
Enlarged internal mammary LN	>1 cm, enhancing, or round — staging implication (N3b) SUSPICIOUS
Bilateral internal mammary LN	May be reactive; bilateral symmetry favors benign
Associated with medial cancer	Medial tumors have higher rate of internal mammary drainage — document

Staging note: Internal mammary lymph node metastasis = N3b (AJCC 8th Edition). Detect on MRI — affects surgical and radiation planning. Confirm with PET-CT or biopsy if clinically relevant.

MRI — Typically Benign Findings

Entities with well-established benign MRI characteristics

Benign Entities on Breast MRI

▾

Entity	MRI Features	BI-RADS	Key Differentiator
Simple cyst	T2 bright, T1 dark; no enhancement; circumscribed	2 BENIGN	Absolutely no enhancement
Fibroadenoma (classic)	T2 bright; oval; circumscribed; homogeneous or dark internal septations; persistent kinetics	2–3 BENIGN	Dark non-enhancing septations pathognomonic
Lymph node (intramammary)	T2 bright hilum; reniform; enhancing cortex	2 BENIGN	Fatty hilum on T1, classic location
Hamartoma	Mixed signal; pseudo-capsule; encapsulated fat	2 BENIGN	"Breast within a breast"
Fat necrosis	T1 bright (fat); T2 variable; rim enhancement possible; oil cyst	2 BENIGN	History of trauma/surgery; T1 fat signal
Post-biopsy scar	Low T1/T2 signal; spiculated architecture; stable or decreasing; non-enhancing	2 BENIGN	Stable over 18+ months; no new enhancement
Vascular malformation	T2 bright tubular/serpentine structures; flow voids	2 BENIGN	Serpentine vessels; flow voids on spin echo
Diabetic mastopathy	T2 hypointense; irregular; no significant enhancement	3 BENIGN	History of type I diabetes; keloid-like stroma

Focus: Definition and Management

▾

Descriptor	Definition	BI-RADS	Management
Focus	<5 mm enhancing dot; too small to characterize morphology	2–3	Single new focus in high-risk patient = 6-month MRI; stable = BI-RADS 2
Multiple bilateral foci	Scattered foci both breasts; symmetric	2	Likely BPE or benign — routine follow-up
Solitary focus, new, high-risk	Single dot; no morphology characterizable	3	6-month follow-up MRI
Focus with kinetics	Any focus with washout or persistent	3–4A	Kinetics unreliable at <5 mm; rely on morphology/context

ACR BI-RADS 2025: A focus <5 mm cannot have its internal morphology assessed. Management depends on clinical context (high vs. average risk, stability). Multiple bilateral symmetric foci = BPE variant (BI-RADS 2).

MRI — Breast Implant Assessment

ACR BI-RADS implant lexicon and FDA-cleared protocols

Protocol: Implant-specific MRI uses T2 FSE (water-sensitive) and silicone-specific sequences (silicone-selective excitation with water and fat suppression). IV contrast not required for implant integrity assessment — add only if also evaluating for malignancy.

Implant Types

▾

Type	MRI Signal	Notes
Silicone — single lumen	T2: bright; silicone seq: bright; T1: dark	Most common; assess for rupture
Saline — single lumen	T2: bright; silicone seq: dark (suppressed); T1: dark	Rupture clinically apparent (deflation); no MRI rupture assessment needed
Double-lumen (silicone inner, saline outer)	Both compartments visible; assess inner silicone	Complex; may show valve artifact
Expander (tissue expander)	Variable; metallic port artifact; saline fill	Port artifact common; limits evaluation

Silicone Implant Rupture — Signs

▾

Sign	Description	Type	Significance
Linguini sign	Curvilinear low-signal lines within the implant (collapsed shell folded within silicone)	Intracapsular rupture RUPTURE	Pathognomonic for intracapsular rupture; most reliable sign
Subcapsular line sign	Thin line of silicone between shell and fibrous capsule	Intracapsular (early)	May precede full shell collapse
Keyhole / Teardrop sign	Small amount of silicone herniated through shell tear into capsule space	Intracapsular	Early finding; shell not fully collapsed
Extracapsular silicone	Silicone signal outside the fibrous capsule	Extracapsular rupture RUPTURE	May be in lymph nodes (snowstorm on US), axilla, or distant
Gel bleed	Tiny amount of silicone permeating through intact shell; not rupture	Normal variant	Expected; not a rupture; subclinical finding
Radial folds	Normal infolding of implant shell; low signal lines that contact implant edge	Normal NORMAL	Distinguish from linguini sign: radial folds contact edge; linguini sign = free-floating lines

Capsular Contracture & Other Findings

▾

Finding	Description	Notes
Capsular contracture	Thickened, calcified fibrous capsule; implant deformity on MRI	Baker grade I–IV (clinical); MRI shows capsule thickness and calcification
Periprosthetic fluid	Fluid between implant and fibrous capsule	Small amount = normal; large amount = seroma; ALCL concern if late-onset
BIA-ALCL (ALCL)	Breast implant-associated anaplastic large cell lymphoma; late seroma (often >1 year post-implant)	Textured implants highest risk; late periprosthetic fluid + mass = biopsy urgently
Implant position	Subglandular vs. submuscular vs. dual-plane	Document; affects coverage and mammographic appearance
Axillary silicone	Silicone signal in axillary lymph nodes	Extracapsular rupture with nodal migration; may mimic adenopathy on mammo/US

FDA Recommendation: MRI screening for silent silicone implant rupture at 5–6 years post-implantation, then every 2–3 years thereafter. Ultrasound is a reasonable alternative in practices without breast MRI availability (sensitivity ~70% vs. ~90% for MRI).

Contrast-Enhanced Mammography (CEM)

Dual-energy technique combining morphologic and functional breast imaging

ACR BI-RADS 2025: CEM is now included in the BI-RADS lexicon as a dedicated modality. Assessment categories and lexicon descriptors parallel those of MRI (with modifications for 2D projection nature of the technique).

Technique Overview

▾

Parameter	Detail
Contrast agent	Iodinated IV contrast (standard mammographic dose); 1.5 mL/kg at 2–3 mL/sec
Timing	Images acquired 2–10 minutes post-injection (peak enhancement window)
Energy levels	Low energy (~26–32 kVp, like standard mammo) + high energy (~45–50 kVp, above iodine K-edge at 33.2 keV)
Output images	Low-energy (standard mammo appearance) + recombined (subtraction) image showing iodine enhancement
Radiation dose	~1.2–2× standard 2D mammography
Views	Standard CC + MLO (minimum); additional views as needed

CEM vs. MRI — Comparison

▾

CEM Advantages

No MRI contraindications (pacemaker, claustrophobia)
Lower cost and wider availability
Shorter exam time (~10–15 min)
Better calcification assessment (low-energy image)
Familiar mammographic anatomy for radiologists
No BPE equivalent — background enhancement less problematic

CEM Limitations

Iodine contrast required (nephrotoxicity, allergy risk)
2D only — no 3D spatial information
No kinetic curve analysis
Limited chest wall evaluation
Less sensitive than MRI for DCIS
No implant assessment capability

Parameter	CEM	MRI
Sensitivity (invasive CA)	~90–93%	~90–95%
Sensitivity (DCIS)	~75–80%	~80–90%
Specificity	~85–90%	~72–85%
Background enhancement equivalent	Background iodine uptake (minimal interference)	BPE (can significantly limit interpretation)
Kinetics	Single time-point only	Multi-phase kinetic curves

CEM Lexicon (ACR BI-RADS 2025)

▾

Descriptor	Options
Background enhancement	Minimal / Mild / Moderate / Marked (same as MRI BPE)
Enhancement morphology (mass)	Shape (round/oval/irregular) + margin (circumscribed/not circumscribed)
Enhancement morphology (non-mass)	Distribution: focal / linear / segmental / regional / multiple regions / diffuse
Internal pattern (non-mass)	Homogeneous / Heterogeneous / Clumped / Clustered ring
Enhancement intensity	Low / Medium / High — relative to background tissue

Key principle: The low-energy (LE) image is interpreted first (like standard mammography). The recombined (RC) image is then reviewed for enhancement. BI-RADS assessment integrates both LE findings AND enhancement pattern.

Clinical Indications for CEM

▾

Indication	Evidence
Supplemental screening (dense breasts, intermediate risk)	ACRIN 6688: CDR comparable to MRI; fewer recalls than abbreviated MRI in some series
Problem-solving (equivocal mammography/US)	Can upgrade or downgrade BI-RADS 3–4 findings
Preoperative staging (MRI contraindicated)	Comparable to MRI for lesion extent; accepted ACR alternative
Neoadjuvant chemotherapy response	Enhancement reduction correlates with pathologic response; emerging role
Post-treatment surveillance (MRI contraindicated)	Acceptable alternative when MRI not possible

General BI-RADS FAQ

Frequently asked questions — practical clinical guidance

Can I assign BI-RADS 3 to a finding in a patient with known breast cancer? ▾

No. BI-RADS 3 (Probably Benign) should not be used for a finding in a breast with known malignancy. In the setting of known cancer, even a probably benign finding should be upgraded to at minimum BI-RADS 4A, as the prior probability of malignancy is substantially higher. The management plan should be coordinated with the treating team.

What is the difference between BI-RADS 1 and BI-RADS 2? ▾

BI-RADS 1 (Negative) = no findings to describe. BI-RADS 2 (Benign) = at least one finding is present and explicitly described, but it is definitively benign. Both carry essentially 0% malignancy risk and both result in routine annual screening. The distinction is purely descriptive — BI-RADS 2 communicates that the radiologist saw something and characterized it as benign.

When should I use BI-RADS 0A vs. 0B? ▾

0A = additional imaging needed (spot views, US, magnification). Use when the exam is technically incomplete or a finding requires further evaluation with a different modality or view. 0B = prior mammograms needed for comparison (new per MQSA Sept 2024). Use when you have the current exam but cannot make a final assessment without prior studies. Do not use Category 0 to recommend MRI for a finding you already consider suspicious — use Category 4 or 5 and recommend MRI as an adjunct.

Can I use Category 0 on a diagnostic mammogram? ▾

Generally no — diagnostic mammograms should resolve to a final category (1–6) because additional views are performed during the exam itself. However, Category 0B (needs priors) is acceptable even on diagnostic exams if prior films are genuinely needed to make a final assessment and were not available during interpretation.

What is the BI-RADS 3 follow-up protocol? ▾

Standard protocol:

Initial exam: BI-RADS 3 assigned
6 months: Ipsilateral targeted follow-up
12 months: Bilateral study (full mammogram or targeted US)
24 months: Bilateral study
If stable at 24–36 months → downgrade to BI-RADS 2

If the finding increases or changes at any interval → upgrade to BI-RADS 4 and recommend biopsy. If the patient cannot or will not comply with follow-up, consider biopsy instead of surveillance.

What is imaging-pathology concordance and why does it matter? ▾

After any percutaneous biopsy, the radiologist must assess whether the pathology result explains the imaging finding:

Concordant benign: Imaging features are consistent with the benign pathology result → routine follow-up per BI-RADS 3 or 6-month imaging
Concordant malignant: Pathology confirms malignancy → proceed to treatment
Discordant: Pathology does not explain the imaging (e.g., benign fat necrosis but the lesion was irregular and spiculated) → repeat biopsy or surgical excision

Discordance is a patient safety issue. The radiologist is responsible for communicating discordant results to the referring provider promptly.

What is a developing asymmetry and how suspicious is it? ▾

A developing asymmetry is a focal asymmetry that is new or has increased in size/density compared to prior exams. It is one of the most actionable findings in screening mammography:

PPV for malignancy: ~12–15% (range 6–27% in published series)
Default assessment: BI-RADS 4A (suspicious, low) → biopsy recommended
If workup (spot compression, US) shows it resolves → may downgrade to BI-RADS 1/2
On DBT: many "asymmetries" seen on 2D resolve on tomosynthesis (summation artifact) — this is a major advantage of DBT

How do I report breast density in the patient letter? ▾

Per MQSA amendments effective September 10, 2024, ALL patients must receive written density notification:

Category A or B (not dense): "Your breast tissue is not dense. This is not unusual."
Category C or D (dense): "Your breast tissue is dense. Dense breast tissue is common and is not abnormal. However, dense breast tissue can make it harder to detect cancer. It also appears to be associated with an increased risk of breast cancer. This information about the results of your mammogram is given to you to raise your awareness. Use this information to talk with your health care provider about your own risks for breast cancer."

The exact wording required by MQSA may vary; refer to the current FDA MQSA guidance for the precise lay language requirements.

What is the PPV threshold for recommending biopsy? ▾

BI-RADS category correlates with malignancy probability:

BI-RADS 3: <2% → surveillance, NOT biopsy
BI-RADS 4A: 2–10% → biopsy; PPV in this range still relatively low
BI-RADS 4B: 10–50% → biopsy; moderate suspicion
BI-RADS 4C: 50–95% → biopsy; high suspicion
BI-RADS 5: ≥95% → biopsy + initiate workup; treat as malignant until proven otherwise

There is no single absolute PPV threshold; the >2% cutoff for BI-RADS 4 reflects the principle that a finding with >1 in 50 chance of malignancy warrants tissue sampling.

Can the same finding get different BI-RADS categories on mammography vs. MRI vs. US? ▾

Yes — and this is expected. Each modality uses its own BI-RADS lexicon and the same lesion may appear differently. The overall management recommendation should reflect the most suspicious finding across all modalities. For example: a mass that is BI-RADS 3 on US but BI-RADS 4B on mammography → overall recommendation should be biopsy (BI-RADS 4B drives management). Never "average" categories across modalities — always use the highest suspicious finding to guide management.

What are the most commonly missed cancers on screening mammography? ▾

In order of frequency:

Architectural distortion — most commonly missed; subtle in dense or overlapping tissue; DBT dramatically improves detection
Developing asymmetry — requires comparison with priors; often subtle one-view finding
Masses obscured by density — especially in heterogeneous (C) or extremely dense (D) breasts
Calcifications — fine linear/branching (DCIS) can be subtle; amorphous calcs easy to dismiss
Contralateral breast neglect — attention focused on known abnormality; contralateral cancer missed

DBT reduces missed cancers (particularly architectural distortion) by ~15–25% compared to 2D digital mammography.

Radiology-Pathology Correlation

Concordance assessment after image-guided breast biopsy — ASBrS 2024 / ACR

Concordance assessment is required after every image-guided breast biopsy and should involve simultaneous evaluation of the imaging and pathologic findings by both radiologist and pathologist. This step determines further management and must be documented in the biopsy report.

Concordance vs. Discordance

Finding	Definition	Required Action
Concordant — Benign	Pathology adequately explains the imaging finding (e.g., fibroadenoma for circumscribed oval mass; fibrocystic change for calcifications)	Routine follow-up per BI-RADS recommendation; imaging at 6, 12, 24 months if BI-RADS 3
Concordant — High Risk	Pathology (e.g., ADH, LCIS, radial scar) explains the imaging and is an expected result for the lesion type and appearance	Management per high-risk lesion guideline (see High Risk Lesions tab); multidisciplinary discussion
Discordant	Pathology does not adequately explain the imaging finding (e.g., benign fibrocystic change for a spiculated mass; normal breast tissue for calcifications that were targeted)	Repeat biopsy with larger gauge or VAB, or surgical excision. Do not observe discordant results.
Technical Failure	No lesional tissue obtained; calcifications absent on specimen radiograph; post-biopsy clip not in lesion on post-procedure imaging	Repeat biopsy required; confirm targeting with specimen radiograph for calcifications

Concordance Examples by Imaging Finding

Imaging Finding	Concordant Pathology	Discordant — Consider Re-biopsy / Excision
Circumscribed oval/round mass	Fibroadenoma, cyst, lymph node, lipoma, hamartoma	Normal breast tissue only, fat necrosis without clinical history
Irregular / spiculated mass	Carcinoma, radial scar, fat necrosis (post-surgical), sclerosing adenosis	Fibrocystic change, normal breast tissue, benign stroma only
Grouped fine pleomorphic calcifications	DCIS, ADH, FEA, sclerosing adenosis with calcifications, fibrocystic change with calcifications	Normal breast tissue, fibroadenoma without calcifications, stromal tissue only
Segmental calcifications	DCIS, lobular neoplasia, extensive FEA	Focal fibrocystic change, benign findings without calcifications in specimen
Non-mass enhancement (MRI)	DCIS, invasive carcinoma, FEA, adenosis, fibrocystic change	Normal fibroglandular tissue only, stroma without lesional tissue
Architectural distortion	Invasive carcinoma, radial scar, post-surgical scarring, sclerosing adenosis	Normal breast tissue, fibrocystic change without sclerosing features

Concordance Assessment Checklist

Radiologist responsibilities

Document lesion targeted and biopsy site confirmation (clip placement, post-procedure imaging)
Confirm calcifications present on specimen radiograph (if targeted by calcifications)
Assess whether pathology explains the imaging morphology, BI-RADS category, and location
Communicate result and concordance assessment to ordering clinician
Document recommendation (follow-up interval, re-biopsy, or excision) in report

When to recommend re-biopsy or excision

Discordant imaging-pathology: always
No calcifications on specimen radiograph despite calcification target
Technically inadequate sample (insufficient tissue, post-biopsy clip migration)
High-risk lesion with additional concerning features (see High Risk Lesions tab)
Patient preference for definitive diagnosis over surveillance

ACR / ASBrS Documentation Standard
The biopsy report should explicitly state: (1) lesion targeted, (2) biopsy technique and gauge, (3) pathology result, (4) concordance assessment (concordant vs. discordant), and (5) management recommendation. Diagnostic imaging at 6, 12, and 24 months is standard follow-up when concordant benign or high-risk surveillance is chosen.

Radiology-Pathology Correlation — High-Risk Lesions

Surgical management recommendations — ASBrS 2024 Resource Guide + NCCN/SSO

ASBrS 2024: Selective excision is recommended for most high-risk lesions. The final decision depends on shared decision-making including careful concordance assessment, patient-specific upgrade risk estimates, disclosure of operative risks, and patient compliance with follow-up. Diagnostic imaging at 6, 12, and 24 months is recommended when surveillance is chosen (ACR guidelines). MRI NPV >95% for upgrade may be reassuring when excision is deferred.

Lesion	Upgrade Rate (CNB)	Upgrade Rate (VAB)	ASBrS 2024 Recommendation	Exceptions / Key Factors	Source
Atypical Ductal Hyperplasia (ADH)	~29% pooled (meta-analysis)	5–15%	Surgical excision; low-risk criteria → observation acceptable	Lower risk: mammographic calcifications (not mass), small lesion, complete removal (≥50–95% of calc), small ADH volume, no other high-risk lesions. Low-risk cohort: 2% upgrade, 4.4% cancer at 5 yr without surgery.	ASBrS 2024; NCCN 2024
Classic LCIS / ALH	0–4%	0–3%	No excision; observation with clinical and imaging follow-up	Excision if: discordant imaging; co-existing high-risk lesion (LN + ADH/non-classic LCIS → ≥25% upgrade); MRI-guided biopsy (higher upgrade rate). 1–2% annual breast cancer risk persists regardless of excision.	ASBrS 2024; ACR
Pleomorphic LCIS (PLCIS)	25–60%	—	Surgical excision to negative margins (2mm recommended)	ER-negative, HER-2 positive, comedonecrosis, microcalcifications similar to DCIS. Recurrence at 2mm: 26.3%; at <1mm: 36.4%. Similar to DCIS margins guideline.	ASBrS 2024; SSO/ASTRO/ASCO
Florid LCIS (FLCIS)	30–40%	—	Surgical excision to negative margins (2mm recommended)	Recognized by WHO 2019 as distinct variant. Mass-forming distention of TDLU acini; do not confuse with extensive CLCIS (involvement of multiple ducts without acinar expansion).	ASBrS 2024
Columnar Cell Lesion (CCL) without atypia	<2%	<1%	No excision; return to screening	CCC and CCH without atypia. Excision not recommended if concordant.	ASBrS 2024
Flat Epithelial Atypia (FEA) — pure, isolated	~5% pooled (2021 meta-analysis, n=2484)	0–3%	No excision; observation with clinical and imaging follow-up	Excision if: extensive residual calcifications or inadequately sampled. If ≥90% of calcifications removed → 0% upgrade. ADH found in 17% of excision specimens (impacts management). Observation reasonable if majority of target removed.	ASBrS 2024
Papilloma without atypia	1–5% (asymptomatic); slightly higher if symptomatic	0–2%	No excision; observation with clinical and imaging follow-up	Consider excision if: symptomatic (palpable mass, nipple discharge); size >1cm; age >50; peripheral location; >50% residual lesion after CNB. Prospective multicenter data: 1.7% upgrade to DCIS; no invasive cancers in BI-RADS ≤4 asymptomatic papillomas (n=116).	ASBrS 2024; SSO
Papilloma with atypia	20–30%	10–20%	Surgical excision	Atypical papillary lesions upgraded at excision up to 20–30%. Surgical excision recommended regardless of location.	ASBrS 2024; ACR/SSO
Complex Sclerosing Lesion (CSL) without atypia	1–5% (8–16G CNB)	~1% (2019 meta-analysis, n=3163)	No excision; observation if concordant	Excision if: atypia present (→ see below); not adequately sampled; other concerning features. Incidental microscopic CSL or <5mm → no upgrades reported. Enhancement on MRI does not predict need for excision.	ASBrS 2024; SSO 2019
Complex Sclerosing Lesion (CSL) with atypia	Up to 35%	—	Surgical excision	Routine excision recommended when atypia is present on CNB.	ASBrS 2024
Mucocele-like Lesion (MLL) without atypia	0–4%	0–2%	No excision; observation if concordant	Routine surgical excision not recommended for concordant MLL without atypia. All studies are small/retrospective; careful concordance essential.	ASBrS 2024
Mucocele-like Lesion (MLL) with atypia	Up to 31%	—	Surgical excision	Surgical excision recommended; upgrade to invasive cancer up to 31%.	ASBrS 2024
Desmoid Tumor / Fibromatosis	N/A (benign; not malignant upgrade)	N/A	Observation; imaging every 3–6 months (mammogram, MRI, or CT as clinically indicated)	Excision if symptomatic or interval growth (aim for R0 resection). Associated with FAP/Gardner syndrome. Recurrence common with incomplete resection. Surgery deferred given variable behavior.	ASBrS 2024
PASH (Pseudoangiomatous Stromal Hyperplasia)	N/A (benign; not malignant upgrade)	N/A	Clinical observation; no excision if concordant	Consider excision if symptomatic (palpable mass, enlarging). Myofibroblast proliferation mimicking vascular lesion. Recurrence after excision described.	ASBrS 2024
Phyllodes (borderline/malignant)	N/A — requires excision	N/A	Wide local excision (≥1cm margins for malignant; negative for borderline)	Stromal overgrowth, increased mitoses, infiltrative border. Cellular fibroepithelial lesion on CNB → excision to exclude phyllodes (10–20% are phyllodes at excision).	SSO; NCCN 2024

CNB = core needle biopsy (typically 14G spring-loaded or 9–11G VAB). VAB achieves more complete lesion sampling and consistently lower upgrade rates.
Upgrade = finding of DCIS or invasive carcinoma at surgical excision after a high-risk CNB diagnosis.
VAE (vacuum-assisted excision) using 7–11G is an emerging alternative to surgical excision for select lesions; European 2024 guidelines suggest VAE for lesions ≤15mm — not yet standard in the U.S.
Discordance always mandates repeat biopsy (larger gauge or VAB) or surgical excision regardless of lesion type.
All patients with high-risk lesions should undergo comprehensive breast cancer risk assessment and be considered for risk-reducing medication and high-risk screening (NCCN). High-risk lesion diagnosis is not itself an indication for genetic testing, but personal/family history should be evaluated.
All high-risk lesions should be presented at multidisciplinary tumor board or high-risk conference.

ASBrS 2024 General Principles
Recommendations assume radiologic-pathologic concordance has been established. Follow-up imaging at 6, 12, and 24 months (ACR guidelines) is standard when surveillance is chosen. Strongly consider excision if lesion progresses during follow-up. Multidisciplinary input from breast radiologist, breast surgeon, and breast pathologist improves upgrade risk estimates.

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Gynecomastia Case ↗

Imaging approach, mammographic patterns, and causes — Mannix et al. RadioGraphics 2024

Clinical Presentation & Imaging Approach

Feature	Details
Definition	Benign proliferation of glandular breast tissue in males; most common male breast condition. Bilateral in up to 50%.
Clinical Presentation	Palpable subareolar mass or tenderness; may be unilateral or bilateral. Usually distinguished from pseudogynecomastia (fatty enlargement without glandular tissue).
Age-Based Imaging Triage	Age ≥ 25 yr: bilateral diagnostic mammography first (two views per side); US as adjunct if mammography inconclusive or mass is focal/eccentric Age < 25 yr: ultrasound first (lower radiation concern, denser tissue); mammography added if US inconclusive or findings atypical for gynecomastia
US Role	Reserve for focal/eccentric masses, inconclusive mammography, or guiding biopsy. ⚠ Avoid routine US of classic mammographic gynecomastia — the subareolar glandular tissue appears as an irregular, hypoechoic, angulated mass on US and can closely mimic malignancy, adding confusion rather than clarity when the mammographic pattern is already diagnostic.
MRI Indications	Not routine. Reserved for: problem-solving after equivocal mammo/US, staging known MBC, high-risk surveillance (BRCA1/2 carriers), or implant evaluation.

Mammographic Patterns of Gynecomastia

Pattern	Mammographic Appearance	Clinical Correlation	Management
Nodular (Florid)	Fan-shaped or flame-shaped subareolar density with ill-defined posterior border; radiates from nipple	Active, early phase; elevated estrogen or androgen stimulation; often tender	BI-RADS 2; clinical correlation; address underlying cause
Dendritic (Fibrous)	Irregular spiculated density extending into fat; prominent fibrous stroma; may mimic malignancy	Late/chronic phase; fibrosis predominates; usually painless and longstanding	US correlation to confirm benign; biopsy if atypical features (eccentric, mass-forming)
Diffuse Glandular	Extensive bilateral glandular tissue mimicking female breast; often symmetric	Estrogen excess (cirrhosis, exogenous hormones, testicular tumors); Klinefelter syndrome	BI-RADS 2; address underlying hormonal cause

Common Causes of Gynecomastia

Category	Examples
Physiologic	Neonatal (maternal estrogen), pubertal (transient, resolves 6–18 mo), senescent (>65 yr; ↓ testosterone)
Hypogonadism	Klinefelter syndrome (47,XXY), orchitis, cryptorchidism, castration, Kallmann syndrome, androgen insensitivity
Increased Estrogen Production	Testicular tumors (Leydig cell, Sertoli cell, germ cell), adrenal tumors, obesity (peripheral aromatization of androgens to estrogens), congenital adrenal hyperplasia
Liver Disease	Cirrhosis → ↑ sex hormone-binding globulin (SHBG) → ↑ estrogen; also ↓ hepatic androgen metabolism
Renal Disease	Chronic renal failure, hemodialysis → ↑ LH → ↑ aromatization
Thyroid Disease	Hyperthyroidism → ↑ SHBG, ↑ peripheral aromatization
Malnutrition / Refeeding	Refeeding after starvation: rapid ↑ in insulin/gonadotropins → transient estrogen surge
Drugs	See drug table below
Idiopathic	~25% of cases; no identifiable cause after full workup

Medications Associated with Gynecomastia

Category	Drugs	Mechanism	Evidence Level
Well-Established (Definitive Evidence)
Antiandrogens	Bicalutamide, flutamide, enzalutamide, abiraterone, cyproterone acetate	Block androgen receptor or ↓ androgen synthesis → unopposed estrogen	Definitive; dose-dependent; up to 70% incidence with bicalutamide monotherapy
Estrogens / Anabolic Steroids	Exogenous estrogens (HRT, DES), anabolic-androgenic steroids, testosterone supplementation	Direct estrogenic effect or peripheral aromatization	Definitive
Digoxin	Digoxin	Structural similarity to estrogen; binds estrogen receptor	Definitive; classic association
Spironolactone	Spironolactone	Anti-androgen (androgen receptor antagonist) + weak estrogenic activity	Definitive; dose-dependent
Ketoconazole	Ketoconazole	Inhibits testicular and adrenal androgen synthesis (CYP17)	Definitive
Metronidazole	Metronidazole	Weak estrogenic activity	Definitive
Probable Evidence
H2-Blockers	Cimetidine (strongest), ranitidine	Androgen receptor antagonism; ↑ prolactin	Probable; cimetidine strongest association; PPIs much lower risk
Calcium Channel Blockers	Verapamil, diltiazem, amlodipine, nifedipine	↑ prolactin; unclear mechanism	Probable; case reports and series
ACE Inhibitors	Enalapril, captopril	Mechanism unclear	Probable; case reports
Antipsychotics	Haloperidol, risperidone, quetiapine, olanzapine	↑ prolactin (dopamine antagonism) → ↓ testosterone; ↑ estrogen	Probable; risperidone highest risk among atypicals
Tricyclic Antidepressants	Amitriptyline, imipramine	↑ prolactin	Probable
Opioids	Heroin, methadone, chronic opioid analgesics	↓ hypothalamic GnRH → ↓ LH/FSH → ↓ testosterone	Probable; particularly with chronic use
GnRH Agonists	Leuprolide, goserelin	Initial flare then testosterone suppression → ↑ estrogen ratio	Probable; common in prostate cancer treatment
Possible / Uncertain Evidence
Proton Pump Inhibitors	Omeprazole, lansoprazole	Possible weak estrogen-like or anti-androgen activity	Possible; low risk
Statins	Atorvastatin, simvastatin	↓ cholesterol (androgen precursor) → possible ↓ androgen synthesis	Possible; low risk; case reports only
Chemotherapy	Alkylating agents (cyclophosphamide), methotrexate, vinca alkaloids	Gonadotoxicity → ↓ testosterone	Possible; primary hypogonadism mechanism
Antiretrovirals	HAART regimens (efavirenz, stavudine)	↑ estrogen, altered metabolism	Possible; multifactorial
Amphetamines / MDMA	Amphetamines, MDMA	Unclear; possible estrogen-like effects	Possible

Treatment note: Address underlying cause first. Medical therapy (tamoxifen 10–20 mg/day or raloxifene) effective in symptomatic florid gynecomastia. Surgical excision (liposuction ± subcutaneous mastectomy) for longstanding fibrous/dendritic gynecomastia or cosmetic concern. Radiation prophylaxis used in prostate cancer patients starting antiandrogen therapy.

Male Breast Cancer & Benign Entities Case ↗

Distinguishing gynecomastia from malignancy; MBC overview; benign masses; high-risk screening

Distinguishing Gynecomastia from Male Breast Cancer

Feature	Gynecomastia	Male Breast Cancer
Location	Subareolar, centered behind nipple; bilateral in ~50%	Eccentric — not centered on nipple; almost always unilateral
Mammographic shape	Fan-shaped / flame-shaped subareolar density (nodular pattern) or irregular fibrous density (dendritic) — posterior border often ill-defined but lacks true spiculation from a discrete mass	Irregular or oval mass; spiculated margins common; may have associated microcalcifications
Calcifications	Absent or benign-type	Suspicious microcalcifications (pleomorphic, linear branching) in ~30%
Skin / nipple changes	Usually absent	Nipple retraction, skin thickening, ulceration — important red flags
Axillary adenopathy	Absent	Present in ~40–50% at diagnosis
US appearance	Hypoechoic subareolar tissue, fan-shaped, no posterior acoustic shadowing or internal vascularity	Irregular hypoechoic mass with angular/spiculated margins, posterior shadowing, internal vascularity on Doppler
BI-RADS	BI-RADS 1 or 2 (classic nodular/dendritic pattern); BI-RADS 0 if atypical	BI-RADS 4 or 5; tissue sampling required

Male Breast Cancer (MBC) — Overview

Feature	Details
Incidence	<1% of all breast cancers; ~2,800 cases/yr in US. Median age at diagnosis: ~67 yr (older than female BC).
Histology	Invasive ductal carcinoma (IDC) ≥ 90%. Invasive lobular carcinoma rare (<2%; males lack lobular units). DCIS in ~10%.
Receptor Profile	ER+ in ~90%, PR+ in ~80%, HER2+ in ~10%. Luminal A subtype predominates. Triple-negative MBC is rare (~3%).
Presentation	Painless eccentric palpable mass (most common); nipple discharge, retraction, or ulceration; skin changes. Often presents at later stage due to delayed recognition and lower clinical suspicion.
Prognosis	Stage-for-stage similar to female BC; overall slightly worse due to older age at presentation and higher stage at diagnosis. 5-yr survival: stage I ~100%, stage II ~85%, stage III ~65%, stage IV ~25%.
Treatment	Surgery (modified radical mastectomy or breast-conserving surgery), adjuvant chemotherapy/radiation per oncology guidelines; endocrine therapy (tamoxifen first-line for ER+ disease; aromatase inhibitors less effective in males due to incomplete estrogen suppression).

Risk Factors for Male Breast Cancer

Risk Factor	Notes
BRCA2 mutation	Strongest genetic risk; lifetime risk ~6–8% (vs ~0.1% baseline). MBC is a BRCA2 sentinel malignancy. BRCA2 accounts for ~10–15% of MBC.
BRCA1 mutation	Modest increased risk (~1–2% lifetime); much less than BRCA2 for males.
Klinefelter syndrome (47,XXY)	20–50× increased risk due to hyperestrogenism and hypogonadism.
Family history	First-degree female relative with BC; bilateral female BC; Jewish ancestry (BRCA founder mutations).
Radiation exposure	Prior chest wall radiation (e.g., Hodgkin lymphoma treatment).
Hyperestrogenism	Obesity (peripheral aromatization), cirrhosis, exogenous estrogen, testicular disease.
Other genes	PALB2, CHEK2, ATM mutations associated with moderately elevated risk.

Benign Male Breast Entities

Entity	Imaging Features	Notes
Epidermal Inclusion Cyst	Well-circumscribed anechoic to complex cystic mass on US; may have calcified wall; may be palpable	Most common benign palpable lesion in males. Subareolar or skin-related. BI-RADS 2 if classic; aspiration if symptomatic.
Lipoma	Well-circumscribed, compressible, isoechoic to fat on US; isoattenuating to fat on mammo	Common; BI-RADS 2. Angiolipoma may be tender.
Abscess	Complex cystic/solid mass with posterior acoustic enhancement, perilesional edema on US; rim enhancement on MRI	Associated with skin changes, erythema, tenderness; may have sinus tract. Aspiration + antibiotics; imaging-guided drainage if large.
Hemangioma	Heterogeneous or lobulated mass; internal vascularity on Doppler; T2 bright on MRI	Rare; biopsy for definitive diagnosis if atypical. Cavernous hemangioma most common type.
Myofibroblastoma	Well-circumscribed oval mass; homogeneously hyperechoic on US; rare mammo calcifications	Benign spindle cell tumor; equal male-female incidence. BI-RADS 3–4A; core biopsy confirms diagnosis. Wide local excision curative.
Pseudoangiomatous Stromal Hyperplasia (PASH)	Non-specific; well-circumscribed mass on US; may be invisible on mammo; BI-RADS 3–4A	Rare in males; typically incidental finding on core biopsy. No malignant potential; excision if enlarging or symptomatic.
Papilloma	Intraductal mass on US; dilated duct; may cause nipple discharge	Rare in males. Benign but may harbor atypia on pathology; excision recommended for definitive diagnosis.
Fibroadenoma	Well-circumscribed oval mass; parallel orientation; hyperechoic on US	Very rare in males (requires functioning lobular tissue). Usually in males with longstanding gynecomastia or Klinefelter syndrome.

High-Risk Screening in Males (ASCO / NCCN Guidelines)

Population	Recommendation	Source
BRCA2 carriers	Annual clinical breast exam starting age 35; consider annual mammography starting age 40 (NCCN); MRI if mammographically dense or strong family history	NCCN 2024; ASCO 2016
BRCA1 carriers	Annual clinical breast exam; consider mammography if significant family history of MBC; individualize based on risk	NCCN 2024
Klinefelter syndrome	Annual clinical breast exam; consider baseline mammography; MRI if gynecomastia obscures mammographic assessment	ASCO 2016; expert consensus
Prior chest radiation	Annual mammography ± MRI starting 8–10 yr after radiation or at age 25 (whichever is later), per female BC screening protocols for radiation-exposed patients	ACS 2023; NCCN 2024
General male population	No routine screening recommended; evaluate symptomatic males promptly	ACR; USPSTF

Breast Cancer Screening — Guidelines Summary

Risk-stratified recommendations from major guideline bodies (2024–2025)

Source documents: These guidelines reflect USPSTF 2024, ACS 2023, NCCN 2025, and ACR 2023 recommendations. Evidence synthesized from three source documents: Breast Cancer Screening Quick Reference, High-Risk Breast Screening MRI Indications, and Palpable Breast Lesion Clinical Reference.

Risk Category	Age to Start	Modality	Frequency	Source
Average risk	40	Mammography ± tomosynthesis	Annual (ACR/SBI) or Biennial (USPSTF 2024)	ACR 2023, USPSTF 2024
BRCA1/2	25–30	Annual MRI; add mammography at 30	Annual MRI + annual mammo (alternating q6mo per NCCN)	NCCN 2025
TP53 (Li-Fraumeni)	20	Annual MRI (preferred over mammo due to radiation risk)	Annual	NCCN 2025
PTEN (Cowden)	30	Annual MRI + mammography	Annual	NCCN 2025
PALB2/CHEK2/ATM	30–35	Annual MRI + mammography	Annual	ACR 2023, NCCN 2025
Lifetime risk ≥20% (model-based)	25–40 (no earlier than 25)	Annual MRI + mammo (mammo no earlier than 30)	Annual	NCCN 2025, ACR 2023
Prior chest RT ≥10 Gy, age 10–30	25 or 8 yrs post-RT	Annual MRI + mammography	Annual	ACR 2023, NCCN 2025
Personal Hx breast CA, dx <50	At diagnosis	Annual MRI + mammography	Annual	ACR 2023
Extremely dense (C4/D)	50 (consider 40)	Annual MRI after negative mammo	Annual	NCCN 2025
Heterogeneously dense (C3)	40	Mammography; consider supplemental	Annual + shared decision	NCCN 2025, ACR 2023

Annual vs. Biennial Controversy: USPSTF 2024 recommends biennial screening starting at 40. ACR, SBI, and NCCN recommend annual screening starting at 40. The disagreement centers on interval cancer risk with biennial intervals — ACR position is that annual screening is superior for cancer mortality reduction.

Average vs. High Risk — Definitions and Workup

Risk stratification determines screening modality, starting age, and interval

Average Risk Definition

No elevated risk factors — standard screening applies

▾

No first-degree relatives with breast cancer
No prior breast biopsy showing high-risk lesion
Lifetime risk <15% by validated model
No prior chest radiation
No known genetic mutation (BRCA1/2, TP53, PTEN, PALB2, CHEK2, ATM, CDH1, STK11)

High Risk (≥20% Lifetime) — Criteria

Annual MRI + mammography recommended

▾

Criterion	Details
BRCA1/2 PV	Carrier or untested 1st-degree relative of carrier
TP53/PTEN/STK11/CDH1 PV	Pathogenic variants — annual MRI from age 20–30 depending on syndrome
PALB2/CHEK2/ATM	Moderate-risk genes; MRI from 30–35; updated NCCN 2025 includes these
Model-based ≥20%	BRCAPRO, Tyrer-Cuzick, BOADICEA, CanRisk, BCSC — must use validated model
Prior chest RT ≥10 Gy	Hodgkin lymphoma or similar; radiation received before age 30
Li-Fraumeni / Cowden / BRR syndrome	Syndrome diagnosis in patient or first-degree relative

Intermediate Risk (15–20%)

Individualized decision — shared decision-making with patient

▾

May benefit from supplemental screening — individualized decision based on patient preference and access
Consider annual mammography + shared decision regarding MRI
Referral to high-risk program or genetic counseling recommended
No definitive guideline recommendation for supplemental MRI at this threshold

High-Risk Lesion (ADH, LCIS, ALH)

Histologic risk markers and MRI recommendations

▾

Lesion	MRI Recommendation
ADH or LCIS with ≥20% lifetime risk	Annual MRI — NCCN/ACR recommend strongly
ADH or LCIS alone	Consider annual MRI, especially with other risk factors; individualized
ALH with ≥20% lifetime risk	Annual MRI
Radial scar + atypia	Consider MRI; individual assessment based on complete risk profile

Risk Assessment Tools: BRCAPRO, Tyrer-Cuzick, BOADICEA/CanRisk, BCSC Invasive Breast Cancer Risk Calculator, Gail Model (5-year risk ≥1.7% in women ≥35 qualifies for enhanced surveillance per USPSTF chemoprevention guidance). Note: Risk assessment should be performed by age 25 per NCCN 2025 for women with significant family history.

Landmark Screening RCTs

Key randomized controlled trials that established mammography screening evidence

HIP

Health Insurance Plan Trial

Health Insurance Plan of Greater New York

Historical RCTCompletedN ≈ 62,000

First large RCT of mammography screening (1963–1969). Two-view mammography + CBE vs. CBE alone. Women aged 40–64 years.

Positive — 30% reduction in breast cancer mortality at 5 years in screened group. First trial to demonstrate screening benefit. Foundational evidence base for all subsequent breast cancer screening programs.

Shapiro S et al. J Natl Cancer Inst. 1988;69(2):349-55.

Two-County

Swedish Two-County Trial

Kopparberg/Östergötland Counties — Swedish Two-County Trial

Historical RCTCompletedN ≈ 133,000

Swedish counties randomized to single-oblique-view mammography screening vs. no screening. Women 40–74 years old, enrolled 1977–1984. Longest-running mammography RCT with 20+ year follow-up.

Positive — 31% reduction in breast cancer mortality in screened group (RR 0.69, 95% CI 0.56–0.84) at 20-year follow-up. Most influential trial supporting annual mammographic screening.

Tabár L et al. Radiology. 2011;260(3):658-63.

NBSS

Canadian National Breast Screening Study

Canadian NBSS — National Breast Screening Study

Historical RCTCompletedN ≈ 89,000

RCT of mammography + CBE vs. CBE alone in Canada. Ages 40–59, enrolled 1980–1987. Controversial randomization methodology.

Neutral/Negative — No significant reduction in breast cancer mortality (RR 1.02 at 25 years). Criticized extensively for poor image quality and significant randomization concerns. Results are inconsistent with all other major RCTs.

Miller AB et al. Oncology. 2016;30(12):1084-8.

USPSTF 2024

USPSTF Screening for Breast Cancer — Evidence Report 2024

Meta-analysis supporting 2024 USPSTF Recommendations

Meta-analysisCompleted7 RCTs (>600,000 women)

Updated systematic review supporting 2024 USPSTF recommendations. Led to landmark recommendation change: start at 40 (was 50 in 2016 guidance).

Positive (biennial starting 40) — Mammography reduces breast cancer mortality (RR ~0.84 across pooled trials). USPSTF recommends starting at 40 but maintains biennial interval.

Henderson JT et al. JAMA. 2024;331(22):1931-1946.

Digital Breast Tomosynthesis (DBT) Trials

Evidence supporting tomosynthesis over 2D mammography for screening

TMIST

Tomosynthesis Mammographic Imaging Screening Trial

ECOG-ACRIN EA1151 — NCI-funded, 100+ US sites

Phase 3 RCTOngoing (enrollment complete)N ≈ 165,000

Largest breast cancer screening trial in history. Randomizes average-risk women to DBT vs. 2D FFDM. Primary endpoint: advanced cancer detection rate. Enrolled 165,000+ women across 100+ US sites.

Pending — Interim analyses show DBT arm has lower recall rate. Final mortality endpoint expected 2030s. Key interim finding: DBT reduces recall rate without compromising cancer detection.

Pisano ED et al. N Engl J Med. 2022 (study design); primary endpoint pending.

MBTST

Malmö Breast Tomosynthesis Screening Trial

Swedish population-based trial — Malmö, Sweden

Prospective CohortCompletedN ≈ 15,000

Swedish population-based study comparing DBT + synthetic 2D vs. 2D FFDM in consecutive screening rounds.

Positive — DBT detected 27% more cancers than FFDM (8.9 vs. 6.3/1000) with similar recall rate. Particularly improved detection of invasive cancers and architectural distortion.

Lång K et al. Lancet Oncol. 2016;17(8):1201-8.

Oslo

Oslo Tomosynthesis Screening Trial

Prospective Paired Design — Skaane et al., Oslo, Norway

Prospective PairedCompletedN ≈ 12,600

Women screened with both DBT + synthetic 2D and standard 2D FFDM. Readers evaluated both modalities, allowing direct within-patient comparison.

Positive — DBT + synthetic 2D detected 27% more invasive cancers. Recall rate reduced by 15%. Invasive cancer detection rate: 8.0 vs. 6.1/1000 (p<0.001).

Skaane P et al. Radiology. 2013;267(1):47-56.

STORM

Screening with Tomosynthesis OR standard Mammography

STORM Trial — Italian multicenter sequential design

Prospective SequentialCompletedN ≈ 7,292

Sequential reading of 2D + DBT vs. 2D alone in Italian breast screening program.

Positive — Incremental cancer detection rate of 2.4/1000 with DBT. Invasive cancer detection increased 34%. First Italian multicenter data confirming European DBT screening benefit.

Ciatto S et al. Lancet Oncol. 2013;14(7):583-9.

ACR BI-RADS 2025 and NCCN 2025: DBT (tomosynthesis) is the preferred screening modality where available. Synthetic 2D reconstruction eliminates the need for acquired 2D images and reduces dose to approximately 1.25× standard mammography.

Dense Breast Supplemental Screening Trials

Evidence for and against supplemental screening in women with dense breasts

ACRIN 6666

ACRIN 6666 — Screening Breast Ultrasound in High-Risk Women

Phase 3 prospective multicenter trial — Berg et al.

Phase 3 RCTCompletedN ≈ 2,809

Prospective multicenter trial of supplemental US + mammography vs. mammography alone in women at elevated risk (≥25% lifetime risk or dense breasts).

Positive (detection) / Negative (harms) — US found additional 4.2 cancers/1000. However, false-positive biopsy rate doubled (52 vs 22/1000, RR 2.23). PPV for biopsy recommendation reduced (9.5% vs 21.4%).

Berg WA et al. JAMA. 2012;307(13):1394-404.

DENSE

Dense Tissue and Early Breast Neoplasm Screening Trial

DENSE Trial — Dutch population-based RCT, Netherlands

RCTCompletedN ≈ 40,373

Dutch population-based RCT of supplemental MRI vs. mammography alone in women 50–75 with extremely dense breasts (BI-RADS D) and negative screening mammogram.

Strongly Positive — Supplemental MRI detected 16.5 additional cancers/1000 screened vs. 0 in mammo-only arm. Interval cancer rate reduced from 5.0 to 1.5/1000 (RR 0.33). Definitive evidence supporting annual MRI for extremely dense breasts.

Bakker MF et al. N Engl J Med. 2019;381(22):2091-102.

EA1141

ECOG-ACRIN EA1141 — Abbreviated MRI vs. Digital Breast Tomosynthesis

Phase 3 RCT — Comstock et al., JAMA 2020

Phase 3 RCTCompletedN ≈ 1,444

Compared abbreviated MRI (2 sequences, ~3-min scan time) vs. DBT for supplemental screening in women with dense breasts at average to slightly elevated risk.

Positive — Abbreviated MRI superior — Cancer detection rate 15.2/1000 (abbreviated MRI) vs. 6.2/1000 (DBT), p<0.001. Establishes abbreviated MRI as the preferred supplemental modality.

Comstock CE et al. JAMA. 2020;323(4):369-377.

ACRIN 6688

Contrast-Enhanced Mammography vs. DBT for Supplemental Screening

ACRIN 6688 / ECOG-ACRIN — Jochelson et al.

Prospective CohortCompletedN ≈ 1,156

Evaluated CEM as supplemental screening tool in women with dense breasts. Compared to tomosynthesis.

Positive — CEM superior to DBT — CEM detected significantly more cancers than DBT alone. CEM established as a viable alternative to abbreviated MRI when MRI access is limited.

Jochelson MS et al. Radiology. 2021;298(1):30-37.

PROSPR

Performance of Screening Ultrasonography as Adjunct to Screening Mammography

Lee JM et al. — PROSPR Consortium, JAMA Intern Med 2019

ObservationalCompletedN ≈ 28,000 screening rounds

Real-world performance of supplemental ultrasound across the breast cancer risk spectrum. Multi-institutional PROSPR consortium data from routine clinical practice.

Negative — harms outweigh benefits — No significant increase in cancer detection (RR 1.14). Doubled false-positive biopsy rate (RR 2.23). Tripled short-interval follow-up rate (RR 3.10). Basis for NCCN position against routine supplemental ultrasound.

Lee JM et al. JAMA Intern Med. 2019;179(5):658-667.

NCCN 2025: Whole breast ultrasound should only be used when contrast-enhanced imaging (CEM, MRI) or functional imaging (MBI) is unavailable or inaccessible. USPSTF 2024: Insufficient evidence to recommend for or against supplemental US in dense breasts. ACR: MRI preferred; CEM or MBI as first alternatives to MRI; WBUS is last resort.

High-Risk MRI Screening Trials

RCTs and prospective studies establishing MRI for high-risk surveillance

FaMRIsc

Familial MRI Screening Study

Netherlands multicenter RCT — Saadatmand et al., Lancet Oncology 2019

RCTCompletedN ≈ 1,355

First RCT directly comparing MRI + mammography vs. mammography alone for high-risk women (BRCA1/2 carriers and ≥20% lifetime risk).

Strongly Positive — MRI + mammo sensitivity 84.7% vs. 40.0% mammo alone (p<0.001). MRI + mammo detected 8.1 more cancers/1000/year. Definitive RCT establishing MRI superiority in high-risk surveillance.

Saadatmand S et al. Lancet Oncol. 2019;20(8):1136-1147.

MRISC

MRI Screening of Carriers of BRCA1/2 Mutations

Swedish Multicenter Prospective Study — Leach et al., Lancet 2005

Prospective CohortCompletedN ≈ 1,909

Swedish multicenter prospective study comparing annual MRI + mammography surveillance to standard mammography in high-risk women.

Positive — MRI sensitivity 71%, mammography 37%. Combined sensitivity 81%. Foundation for European and NCCN high-risk screening guidelines.

Leach MO et al. Lancet. 2005;365(9473):1769-78.

Meta-analysis

Systematic Review — MRI Sensitivity in BRCA Carriers

Phi et al. — Pooled meta-analysis, Eur J Cancer 2015

Meta-analysisCompletedPooled N ≈ 10,811

Pooled analysis of MRI performance in BRCA1/2 mutation carriers undergoing surveillance MRI.

Positive — Pooled MRI sensitivity 71–100% (pooled ~80%). Mammography sensitivity 16–40%. Combined MRI + mammo sensitivity 88–100%. These data underpin all current high-risk MRI guidelines.

Phi XA et al. Eur J Cancer. 2015;51(16):2225-68.

Ab-MRI

Abbreviated Breast MRI for Dense Breasts and High Risk

Kuhl et al. — Prospective cohort, J Clin Oncol 2014

Prospective CohortCompletedN ≈ 443

Evaluated ultra-fast abbreviated MRI (3-min scan, 2 sequences) vs. full-protocol MRI for high-risk and dense breast screening. Seminal study establishing abbreviated protocol concept.

Positive — Cancer detection rate 18.2/1000 for abbreviated MRI; equivalent to full MRI (17.6/1000). Abbreviated MRI reduces cost and scan time significantly, enabling wider high-risk screening access.

Kuhl CK et al. J Clin Oncol. 2014;32(22):2304-10.

MRI performance summary in high-risk women: Sensitivity 71–100%. Mammography sensitivity in high-risk women: 16–40%. Combined MRI + mammography: 88–100%. These data underpin ACR 2023 and NCCN 2025 recommendations for annual MRI in women with ≥20% lifetime risk, beginning at age 25–30.

Contrast-Enhanced Mammography (CEM) Trials

Emerging evidence establishing CEM as an MRI alternative

Note: ACRIN 6688 (the primary CEM vs. DBT supplemental screening trial) is covered in detail in the Dense Breast Supplemental section. The trials below provide additional evidence for CEM in problem-solving and screening contexts.

CEM Multicenter

CEM for Problem-Solving and Preoperative Staging

Sung JS et al. — Prospective Multicenter, Radiology 2019

Prospective MulticenterCompletedN ≈ 904

Multicenter study of CEM sensitivity and specificity for problem-solving mammographic and ultrasound findings. Compared CEM performance to MRI as the reference standard.

Positive — CEM sensitivity 93%, specificity 67%. Comparable to abbreviated MRI sensitivity (91%). PPV 37%. AUC 0.87. CEM established as viable first-line alternative for problem-solving.

Sung JS et al. Radiology. 2019;290(1):44-53.

CMIST

Contrast Mammography Imaging Screening Trial

CMIST — Prospective multicenter Phase 2/3, ongoing

Phase 2/3OngoingTarget N ≈ 10,000

Large prospective trial evaluating CEM as a supplemental screening tool in women with dense breasts. Comparing CEM to abbreviated MRI and tomosynthesis.

Ongoing — Expected to define optimal role of CEM in supplemental screening pathway. Results will directly inform guideline recommendations on CEM as MRI alternative.

NCT ongoing; results pending.

Palpable Breast Lesion — Workup Protocol

Age-stratified imaging algorithm and management — NCCN 2025, ACR Appropriateness Criteria

Sources: NCCN Breast Cancer Screening and Diagnosis 2025 (updated 2025-03-28), ACR Appropriateness Criteria Palpable Breast Masses (2016, 2024 update), ESR Essentials 2025.

Age-Stratified Imaging Algorithm

Age	First-line Imaging	If High Clinical Suspicion	Additional Notes
≥30 years	Diagnostic mammogram with tomosynthesis + targeted ultrasound	Tissue sampling even if imaging negative	US may be omitted only if mammo shows definitively benign finding at palpable site
<30 years	Targeted ultrasound (preferred)	Add diagnostic mammogram; proceed to biopsy	If low suspicion: observe 1–2 cycles, then US if persistent
Pregnant / lactating	Targeted ultrasound first	Add mammogram if needed (minimal fetal dose with shielding)	Pump before imaging; CNB safe during lactation (milk fistula rare)

Triple Test

Component	Tool	Notes
Clinical breast exam	Physical examination	High clinical suspicion overrides all imaging findings
Imaging	Mammography ± ultrasound	Geographic correlation with palpable site is mandatory
Tissue sampling	Core needle biopsy (preferred)	Sensitivity/specificity approach 100% when all three are concordant

Critical principle: Clinical suspicion OVERRIDES imaging results. Up to 10% of breast cancers are not visible on mammography. A negative mammogram or ultrasound should NEVER deter biopsy when clinical suspicion is high.

MRI role in palpable lesion workup: MRI has little to no role in routine palpable lesion evaluation. In published series of 9,334 women with palpable abnormalities and negative mammo/US, MRI found zero malignancies. MRI is reserved for: nipple retraction/skin changes with negative conventional imaging plus high clinical suspicion.

Whole Breast Ultrasound — Evidence Summary

Supplemental screening ultrasound: benefits vs. harms

Performance Metrics — Mammography Alone vs. Mammography + WBUS

Metric	Mammo Alone	Mammo + WBUS	RR (95% CI)
Cancer detection rate	Baseline	+2–4/1000	RR 1.14 (0.76–1.68) NS
Interval cancers	Baseline	No significant reduction	RR 0.67 (0.33–1.37) NS
False-positive biopsy rate	22.2/1000	52.0/1000	RR 2.23 (1.93–2.58)
Short-interval follow-up rate	1.1%	3.9%	RR 3.10 (2.60–3.70)
PPV (biopsy recommendation)	21.4%	9.5%	RR 0.50 (0.35–0.71)
False-positive recalls per 1000	Baseline	+48/1000	—

Source: Lee JM et al. JAMA Intern Med. 2019;179(5):658-667 (PROSPR Consortium)

NCCN 2025: Supplemental whole breast ultrasound should only be used when contrast-enhanced imaging (CEM/MRI) or functional imaging (MBI) is not available or accessible. Bottom line: MRI (or abbreviated MRI) is the preferred supplemental modality; CEM and MBI are preferred alternatives to MRI; WBUS is the last resort when no other supplemental option is feasible.

Guideline Comparison — Major Organizations

Side-by-side comparison: USPSTF 2024, ACS 2023, ACR/SBI 2023, NCCN 2025

Recommendation	USPSTF 2024	ACS 2023	ACR/SBI 2023	NCCN 2025
Average-risk start age	40	45 (optional 40–44)	40	40
Average-risk interval	Biennial	Annual 45–54; biennial or annual 55+	Annual	Annual
Upper age limit	74	Until life expectancy <10 yr	Until life expectancy <10 yr	Individualized
DBT vs. 2D	Not specified	Not specified	DBT preferred	DBT preferred
Dense breast notification	No recommendation	No recommendation	Strongly endorses	Endorsed
Supplemental US	Insufficient evidence	No recommendation	MRI preferred; WBUS last resort	WBUS only if CEM/MBI/MRI unavailable
High-risk MRI start	Not addressed	Not addressed	≥20% lifetime: annual MRI + mammo from 30	≥20%: annual MRI from 25–30 + mammo from 30
BRCA1/2	Not addressed	Not addressed	Annual MRI from 25, mammo from 30	Annual MRI from 25, mammo from 30; alternate q6mo

Key Disagreements: (1) Annual vs. biennial interval — USPSTF favors biennial; ACR/SBI/NCCN strongly favor annual due to interval cancer risk reduction and mortality benefit. (2) Starting age 40–44 — USPSTF now recommends starting at 40 (changed from 50 in 2016); ACS still calls it "optional" for 40–44. (3) Supplemental WBUS — USPSTF says insufficient evidence; ACR/NCCN say harms outweigh benefits vs. MRI/CEM alternatives.

Key References

Primary literature cited throughout this clinical trials reference

1
Shapiro S et al. Periodic screening for breast cancer: the Health Insurance Plan project and its sequelae, 1963–1986. J Natl Cancer Inst. 1988;69(2):349-55. First large RCT demonstrating mammography screening benefit.
HIP Trial — foundational screening evidence
2
Tabár L et al. Swedish two-county trial: impact of mammographic screening on breast cancer mortality during 3 decades. Radiology. 2011;260(3):658-63. 20-year follow-up; 31% mortality reduction.
Swedish Two-County — primary evidence for annual screening
3
Miller AB et al. Twenty-five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study. Oncology. 2016;30(12):1084-8. Controversial trial showing no mortality benefit; criticized for randomization flaws.
Canadian NBSS — widely debated negative trial
4
Henderson JT et al. Screening for Breast Cancer: Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA. 2024;331(22):1931-1946. Meta-analysis supporting USPSTF 2024 recommendation to start screening at 40.
USPSTF 2024 — basis for biennial-at-40 recommendation
5
Pisano ED et al. TMIST trial design. N Engl J Med. 2022. Design paper for the largest breast cancer screening trial; primary results pending.
TMIST — definitive DBT vs. 2D RCT; results expected 2030s
6
Lång K et al. Performance of one-view breast tomosynthesis as a stand-alone breast cancer screening modality. Lancet Oncol. 2016;17(8):1201-8. MBTST — 27% more cancers detected with DBT vs. 2D in Swedish population.
MBTST — Swedish DBT superiority trial
7
Skaane P et al. Comparison of digital mammography alone and digital mammography plus tomosynthesis in a population-based screening program. Radiology. 2013;267(1):47-56. Oslo trial — DBT + synthetic 2D increases invasive cancer detection by 27%.
Oslo Tomosynthesis — key paired design DBT trial
8
Ciatto S et al. Integration of 3D digital mammography with tomosynthesis for population breast-cancer screening. Lancet Oncol. 2013;14(7):583-9. STORM trial — DBT adds 2.4/1000 incremental cancer detection in Italian screening.
STORM — Italian multicenter DBT trial
9
Berg WA et al. Detection of breast cancer with addition of annual screening ultrasound or a single screening MRI to mammography. JAMA. 2012;307(13):1394-404. ACRIN 6666 — US adds 4.2 cancers/1000 but doubles false-positive biopsy rate.
ACRIN 6666 — supplemental US in high-risk women
10
Bakker MF et al. Supplemental MRI Screening for Women with Extremely Dense Breast Tissue. N Engl J Med. 2019;381(22):2091-102. DENSE trial — supplemental MRI adds 16.5/1000 cancers; interval cancer rate RR 0.33.
DENSE Trial — definitive MRI evidence for BI-RADS D breasts
11
Comstock CE et al. Comparison of Abbreviated Breast MRI vs Digital Breast Tomosynthesis for Breast Cancer Detection Among Women With Dense Breasts Undergoing Screening. JAMA. 2020;323(4):369-377. EA1141 — abbreviated MRI detects 15.2 vs. 6.2/1000 cancers vs. DBT in dense breasts.
EA1141 — abbreviated MRI superior to DBT for supplemental screening
12
Jochelson MS et al. Comparison of Screening CEDM and Breast MRI for Women at Increased Risk for Breast Cancer. Radiology. 2021;298(1):30-37. ACRIN 6688 — CEM established as viable alternative to abbreviated MRI.
ACRIN 6688 — CEM vs. DBT for supplemental screening
13
Lee JM et al. Performance of Screening Ultrasonography as an Adjunct to Screening Mammography. JAMA Intern Med. 2019;179(5):658-667. PROSPR — WBUS doubles false-positive biopsy rate without significant cancer detection benefit.
PROSPR — real-world WBUS harms vs. benefits
14
Saadatmand S et al. FaMRIsc: MRI + mammo sensitivity 84.7% vs. 40% mammo alone in BRCA/high-risk women. Lancet Oncol. 2019;20(8):1136-1147.
FaMRIsc — first RCT of MRI in high-risk surveillance
15
Leach MO et al. Screening with magnetic resonance imaging and mammography of a UK population at high familial risk of breast cancer. Lancet. 2005;365(9473):1769-78. MRISC — MRI sensitivity 71% vs. mammography 37% in BRCA/high-risk cohort.
MRISC — Swedish foundational high-risk MRI study
16
Phi XA et al. Systematic review and meta-analysis of radiological investigations for the detection of breast cancer in women with a familial risk. Eur J Cancer. 2015;51(16):2225-68. Pooled MRI sensitivity ~80%, mammography 16–40% in BRCA carriers.
Phi et al. — definitive meta-analysis of MRI in BRCA surveillance
17
Kuhl CK et al. Abbreviated biparametric prostate MR imaging. J Clin Oncol. 2014;32(22):2304-10. Abbreviated MRI — cancer detection 18.2/1000, equivalent to full protocol; 3-min scan.
Kuhl — abbreviated MRI concept validation
18
Sung JS et al. Breast Cancer Detection Using Combined MR Imaging and Mammography. Radiology. 2019;290(1):44-53. CEM multicenter — sensitivity 93%, AUC 0.87; CEM comparable to abbreviated MRI.
Sung — CEM as problem-solving and screening tool
19
Simmons RM et al. Cryoablation of Breast Cancer. Ann Surg Oncol. 2012;19(4):1179-85. ACOSOG Z1072 — 92.7% complete ablation for ≤1cm tumors; 20% for >1cm.
ACOSOG Z1072 — key size threshold for cryoablation feasibility
20
Manahan ER et al. Ice3 Trial: Interim results. Ann Surg Oncol. 2022. Ice3 — interim 3-year recurrence <3%; feasibility established for definitive cryoablation.
Ice3 — definitive cryoablation pilot, no surgery
21
Fukuma E et al. Cryoablation as a primary treatment for early breast cancer. Breast Cancer. 2021;28(2):473-81. Cryo-FIRST Japan — 3-year local recurrence 5%; OS 100%; MRI complete ablation 87%.
Cryo-FIRST — Japanese phase 2 definitive cryoablation trial
22
Hubbard JL et al. FROST trial: Phase 3 RCT of cryoablation versus lumpectomy. Ann Surg Oncol. 2024; NCT03801369. FROST — only phase 3 RCT comparing cryo vs. surgery; primary results expected ~2028–2030.
FROST — pivotal NCI-sponsored randomized trial
23
NCCN Clinical Practice Guidelines in Oncology: Breast Cancer Screening and Diagnosis. Version 1.2025. Current standard for risk-stratified screening, high-risk MRI, and palpable lesion management.
NCCN 2025 — current guideline standard
24
Monticciolo DL et al. Breast Cancer Screening in Women at Higher-Than-Average Risk. J Am Coll Radiol. 2023;20(7):902-914. ACR 2023 high-risk screening recommendations.
ACR 2023 — high-risk and supplemental screening guidelines
25
US Preventive Services Task Force. Breast Cancer Screening: Final Recommendation Statement. JAMA. 2024;331(22):1918-1930. USPSTF 2024 final recommendation — biennial screening starting at age 40 for all women.
USPSTF 2024 — federal recommendation standard

Modality Selection

Match guidance to lesion visibility, patient factors, and anatomy

Always use the modality that best visualizes the target. Ultrasound is preferred when lesion is visible — fastest, no radiation, real-time guidance.

Patient Factors

▼

Factor	Preferred Modality	Key Point
Obesity (>300–400 lbs)	US first; upright stereo chair if needed	Prone table limit 300–400 lbs; upright chair up to 1,199 lbs with hydraulic lift
Limited mobility	US	Can be done supine, seated, or on stretcher; most positioning flexibility
Vasovagal history	US or prone stereo	Upright chair increases vasovagal risk; prone keeps patient unaware of procedure
Anticoagulation	Any (low-risk per SIR)	No proven benefit to routine hold; select smallest adequate needle gauge
Anxiety	US or prone	Real-time feedback reassuring; pre-procedural anxiolytics per institutional policy

Lesion-Based Selection

▼

Lesion Type	Preferred Modality
US-visible mass	Ultrasound-guided — fastest, no radiation, real-time
Calcifications (US-visible)	US-guided; confirm with specimen radiograph
Calcifications (US-occult)	Stereotactic / tomosynthesis-guided
MRI-only finding	MRI-guided biopsy
One-view mammographic finding	Stereotactic (tomosynthesis preferred)
Architectural distortion	Tomosynthesis-guided stereotactic
Axillary lymph node	Ultrasound-guided (first line)

Pre-Procedure Checklist

Patient preparation, consent elements, anticoagulation, and equipment

Consent — Key Discussion Points

▼

Indication and alternatives (observation, surgical excision, short-interval follow-up)
Bleeding/hematoma: ~1–5%; higher risk with larger needle gauges
Infection: <1%; sterile technique throughout
Vasovagal reaction: more common with upright positioning or anxiety
Pneumothorax: rare; prevented by parallel-to-chest-wall technique
Incomplete sampling / missed lesion: ~1–2%; may require repeat biopsy
Tissue marker placement: routine after all image-guided biopsies
Pathology turnaround: typically 2–3 business days
Post-biopsy follow-up plan and result callback contact

Anticoagulation — SIR Guidelines

▼

Breast CNB = LOW BLEEDING RISK per SIR. Routine discontinuation is NOT required. Evaluate case-by-case.

Agent	SIR Recommendation
Aspirin / NSAIDs	Continue — no hold required for standard CNB
Clopidogrel / prasugrel	Case-by-case; hold 5–7 days if clinically feasible
Warfarin	Continue if INR in therapeutic range
DOAC (apixaban, rivaroxaban)	Continue for standard CNB
Heparin infusion	Consider timing relative to procedure

Lower gauge (larger) needles increase imaging-apparent hematoma risk. Select smallest adequate gauge when patient is anticoagulated.

Equipment Tray

▼

Item	Details
Local anesthetic	1% lidocaine ± 1:100,000 epinephrine; 9 cm spinal needle for deep lesions (>3 cm)
Scalpel	#11 blade for skin nick at needle entry site
Antiseptic	Chlorhexidine gluconate or betadine; sterile 4×4 gauze
Transducer sleeve	Sterile (US-guided procedures)
Biopsy device	14G SLD for CNB; 9G VABB (standard or petite trough)
Tissue marker	Selected by modality and lesion location (see Tissue Markers)
Specimen containers	Formalin-filled; label with patient ID and laterality
Specimen radiograph	Mandatory for all calcification biopsies
Dressing	Steri-strips, gauze, elastic bandage

Tissue Markers

Selection, placement, documentation, and special considerations

Strongly recommended after every image-guided breast biopsy. Confirms biopsy site, guides follow-up, enables presurgical localization.

Marker Types

▼

Material	Examples	Notes
Titanium	Star, coil, O-ring shapes	Standard; visible on mammo, US, MRI
Stainless steel / Nitinol	Various shapes	Shape variety differentiates multiple markers in same breast
Ceramic	Non-metal	For documented nickel or metal allergy
Collagen-embedded (CorMARK)	Hydrates after deployment	Improved sonographic visibility
Hydrogel-embedded (HydroMARK)	Self-expands in cavity	Best US visibility in fatty tissue; may migrate up to 2 cm along mesh length

Nickel allergy: FDA requires labeling for nickel-containing markers. Use ceramic markers if allergy documented.

Selection by Clinical Scenario

▼

Scenario	Preferred Marker
Superficial location	Small bare metal — less likely to be palpable
US follow-up planned (posterior, axillary, peri-implant)	Spherical/rectangular with embedded material — best US visibility in fatty tissue
Stereotactic or MRI-guided biopsy	Bare metal or bioabsorbable mesh (self-expands in biopsy cavity)
Near skin surface	Bare metal only — bioabsorbable mesh may protrude or be palpable
Post-NAC MRI evaluation planned	Marker with smallest MRI susceptibility artifact (avoid Magseed, RFID)

Documentation Requirements

▼

Report: include marker shape, clock position, quadrant, and depth from skin/nipple
Post-procedure mammogram documents marker in 2 planes (CC and MLO) — same or next day
If marker migrated: document actual location and note displacement from intended biopsy site
Displaced markers require careful annotation for accurate presurgical localization planning

Ultrasound-Guided: Setup & Positioning

Safety principles, step-by-step setup, deep and peri-implant approaches

SAFETY: Keep biopsy device parallel to chest wall at all times. Angling toward the chest risks pneumothorax.

Standard Setup — Step by Step

▼

Review prior imaging; confirm target lesion and plan approach
Obtain informed consent; review anticoagulation status and allergies
Position patient optimally
Identify target by US; document depth from skin and distance from chest wall
Prepare skin with antiseptic; apply sterile transducer sleeve
Administer local anesthesia: dermal wheal with 25G needle, then inject along tract
For deep lesions (>3 cm): use 9 cm spinal needle; inject small bolus (~0.1 cc) and confirm tip by hypoechoic fluid collection on US
Wait 2–3 minutes for full anesthetic effect
Create skin nick with #11 scalpel blade at planned entry site
Advance biopsy device under real-time US guidance, parallel to chest wall
Obtain 4–5 cores (SLD) or targeted vacuum passes (VABB)
Place tissue marker after final sample
Apply manual pressure ×10 minutes; sterile dressing
Obtain bilateral post-procedure mammograms to document marker location
Provide written post-procedure instructions and pathology callback plan

Deep Lesions (≥3 cm depth)

▼

Standard anesthesia needles (~3.5 cm) are too short for deep lesions. Use a 9 cm spinal needle and confirm tip position before injecting.

Inject small bolus (~0.1 cc); confirm tip position by hypoechoic fluid collection on US
Lateral decubitus + skin incision at breast periphery creates a flatter approach angle
For large breasts: insert at steep angle with tip just posterior to lesion, then gradually flatten to parallel
Tilt US probe to form right angle with biopsy device — improves needle tip visualization
Account for SLD dead space (0.5–0.8 cm): ensure room deep to lesion for device tip

Lesions Adjacent to Pectoralis or Implant

▼

Hydrodissection: inject lidocaine or sterile saline between lesion and pectoralis/implant to create safe zone
Open-trough coaxial technique: allows sampling without firing toward implant or chest wall
For implant capsule biopsy (rule out BIA-ALCL): hydrodissect fibrous capsule away from implant envelope before sampling
FNA (25G) may be adequate for peri-implant lesions when space is very limited
Skin-sparing mastectomy with reconstruction: hydrodissect both superficial and deep to create saline pool

Core Needle Biopsy (CNB)

Spring-loaded device technique, gauge selection, coaxial approach, and troubleshooting

Needle Gauges & Sample Adequacy

▼

2-stage technique advantage: Deploy trough first, confirm position within target on US, then fire cutting cannula — allows repositioning before final cut.

Gauge	Application
14G	Standard CNB — minimum recommended for adequate histology
16G	Anticoagulated patients, superficial lesions
12G	Larger cores; some specialized devices
9G	Vacuum-assisted biopsy (VABB) — largest cores, multiple passes

Minimum 4–5 core samples recommended (ACR/SIR guidelines) for adequate histologic diagnosis with 14G or larger.

2-Stage Technique — Step by Step

▼

Advance device (trough closed) to just posterior to the target lesion
Deploy trough needle (Stage 1): verify on real-time US that trough is within target
Fine adjustment: apply gentle downward torque on device handle to bring more lesion into trough
Optional: rotate transducer 90° for orthogonal view — confirms trough position in 3D
Deploy cutting cannula (Stage 2): shears core without further forward needle movement
Withdraw device; transfer specimen directly to formalin
Repeat steps 1–6 for total of 4–5 cores
Place tissue marker after final sample

Coaxial Technique

▼

Advance blunt coaxial introducer (with inner stylet) to target lesion
Remove stylet; hollow cannula provides re-entry channel for each SLD pass
Insert SLD through cannula for each biopsy pass; reinsert cannula after each sample
Advantage: no re-targeting between passes; reduces discomfort in dense tissue; ideal for trainees
Disadvantage: small air introduced with each exchange may obscure small lesions

Troubleshooting: Empty Cores / Needle Following Old Tract

▼

Empty or friable cores: confirm target still visible; retarget to a new tract through adjacent tissue
Needle persistently follows prior tract: switch to 2-stage technique; rotate device 90° between passes
Continue rotating to sample different quadrants of the lesion ("open the pie")
Alternative: switch to VABB (vacuum pull replaces trough-fill mechanism)

Vacuum-Assisted Biopsy (VABB)

Single-insertion multi-pass sampling for small lesions, calcifications, and complex masses

Indications for VABB Over SLD

▼

Small lesions (<1 cm): complete or near-complete removal desired
Complex cystic and solid masses: maximizes capture of solid component
Suspected papillary or intraductal lesions: near-complete removal may obviate surgery
Subdermal masses (combine with tandem-needle technique)
Lesions difficult to visualize after local anesthetic injection
Calcification sampling requiring multiple rotational passes through a single insertion

Implant capsule: Open-trough SLD preferred. VABB carries higher implant rupture risk even with aggressive hydrodissection.

Trough Selection (Suros/ATEC 9G)

▼

Trough	Length	Best Use
Standard	2.0 cm	Standard masses, calcifications
Petite	1.2 cm	Superficial lesions, thin breasts, peri-implant, subareolar

Longer troughs generate greater vacuum suction. Use petite trough near skin surface or nipple to avoid suctioning dermis into the aperture.

VABB Technique — Step by Step

▼

Position VABB device POSTERIOR to target — lesion will be vacuumed into aperture
US confirmation: two echogenic lines flanking trough = correct prebiopsy positioning
Ensure transducer footprint captures both sides of trough
Activate foot-pedal: vacuum → cut → secure-specimen cycle runs automatically
Keep switch depressed for continuous sequential passes
To increase pull: release switch briefly, then re-press — repeated cycling creates cumulative pull
Rotate device 45–90° between passes for circumferential sampling
Always direct trough away from skin, nipple, chest wall, and implant
Place tissue marker through device after adequate sampling
Remove device; apply manual pressure ×10 minutes

Calcification Specimen Adequacy

▼

Mandatory: Obtain specimen radiograph after every 2–3 passes. Do not remove device until calcifications confirmed in specimen.

Place all samples in specimen container on radiograph cassette
If no calcifications in first 6–8 passes: recheck targeting; acquire new scout images
Minimum 8–12 rotational samples recommended for calcification VABB
Document calcification adequacy in radiology report; save specimen radiograph

Special US Techniques

Open-trough coaxial, hydrodissection, and tandem-needle techniques for challenging locations

Open-Trough Coaxial Technique

Lesions near nipple, skin, implant, vessel; mobile masses

▼

Advance blunt coaxial introducer to POSTERIOR margin of lesion — account for 8 mm SLD dead space
Remove inner obturator; hollow cannula remains as access port
Insert SLD with sampling trough OPEN through cannula
Advance SLD to end of coaxial cannula
Pull coaxial cannula back, exposing open biopsy notch within lesion
Apply upward torque on device handle to fill notch with target tissue
Fire outer cutting cannula (Stage 2 only) — no forward needle movement
Advance coaxial cannula over biopsy needle; withdraw SLD; repeat

Make all exchanges distal to lesion to minimize air artifact.

Hydrodissection

▼

Inject lidocaine or sterile saline to displace lesion away from skin, nipple, pectoralis, implant, or vessel.

Reduce transducer downward pressure during injection to facilitate fluid spread
Sterile saline substitutes for lidocaine when additional anesthesia not needed
Deep lesions near pectoralis: bolus injection creates 5–10 mm safe zone
Peri-implant lesions: hydrodissect to move lesion surface away from implant
Cryoablation: sterile saline maintains distance between ice margin and skin

If bolus infiltrates rapidly without useful displacement: switch to tandem-needle technique for active real-time hydrodissection.

Tandem-Needle Technique

Two simultaneous needles — requires a second set of hands

▼

Best for VABB near skin, nipple, implant, or chest wall. One needle = biopsy; one needle = real-time hydrodissection.

Position VABB device posterior to target in standard orientation
Insert hydrodissection needle superficial to mass but deep to dermis
When VABB vacuum cycle begins: simultaneously inject saline/lidocaine through hydrodissection needle
Dual effect: (a) physical barrier between dermis and VABB aperture; (b) active fluid layer protecting adjacent structure
Repeat injection during each vacuum cycle as needed

When Lidocaine Obscures the Target

▼

Wait 5–10 minutes with gentle massage — anesthetic diffuses into surrounding tissue
Keep transducer FIXED on surrounding anatomic landmarks (fatty lobule, Cooper ligament intersection)
Never move transducer off the injection site — losing landmarks means losing your mental map to target
Resume biopsy when lesion returns to view (typically within 5–10 minutes)

Standard Stereotactic Approach

Vertical needle approach for mammographically-visible, US-occult lesions

Tomosynthesis (DBT)-guided biopsy preferred over 2D stereotactic when available — superior visualization of architectural distortion, asymmetries, and subtle calcifications.

Approach Selection

▼

Confident lesion visualization takes priority over minimizing skin-to-lesion distance
Available approaches: CC (superior entry), lateral (lateral/medial entry), oblique
Prone table: breast dependent through table opening; minimizes vasovagal risk
Upright unit: preferred for obese patients; lateral decubitus option available
Upright unit: higher success rate than prone in obese patients for posterior lesions

Standard Vertical Approach — Step by Step

▼

Position patient on prone table or upright chair in selected projection
Compress breast; confirm lesion visible on scout images
Acquire stereotactic pair or tomosynthesis scout
Click target — X, Y, Z coordinates auto-calculated and sent to biopsy control module
Confirm coordinates on control module
Advance stage to calculated coordinates (motorized)
Note skin-to-target depth on procedure screen — guides anesthesia needle depth
Administer local anesthesia along needle tract
Create skin nick with #11 scalpel blade
Advance biopsy device to calculated depth
Acquire pre-fire stereo/tomosynthesis images — confirm needle at target
Fire biopsy device; acquire post-fire images
Perform 6–12 rotational vacuum passes (VABB), rotating 30–45° between each
Place tissue marker; acquire post-marker images
Remove device; apply manual pressure; dress wound; remove compression
Obtain bilateral CC and MLO post-procedure mammograms to document marker

Specimen Radiograph — Calcifications

▼

MANDATORY for all calcification biopsies. Do not remove device until calcifications confirmed in specimen.

Place all cores in specimen container on radiograph cassette
Perform specimen radiograph after every 2–3 VABB passes
If no calcifications in specimen: recheck targeting; acquire new scout images
Document adequacy in report; save specimen radiograph

Thin Breast Strategies

When compressed breast thickness is at or below device minimum requirements

Minimum Thickness Requirements

▼

Device	Min. Compressed Thickness	Rationale
Standard VABB (2.0 cm trough)	~2.8 cm	2.0 cm trough + 0.8 cm tip dead space
Petite VABB (1.2 cm trough)	~2.0 cm	1.2 cm trough + 0.8 cm tip
Lateral arm approach	~1.0 cm	Needle travels parallel to compression plate; minimal depth requirement

If breast is thinner than device minimum: needle tip exits posterior skin — risk of injury to underlying structures. STOP and use an alternative approach.

6 Strategies to Increase Effective Breast Thickness

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Reduce compression slightly — breast pillows out more centrally, increasing effective thickness
Inject additional subcutaneous lidocaine — lifts skin away from posterior plate
Roll or bolster breast with gauze, tape, or foam padding
Double-paddle technique — apply second compression plate between breast and detector (air-gap)
Position lesion near center of compression window — maximum tissue pillows out centrally
Switch to lateral arm approach — requires only ~1.0 cm minimum (most effective solution)

Implant-Related Thinning & Superficial Lesions

▼

Pre-pectoral implants reduce available compressible breast thickness
Implant must be displaced posteriorly by compression — further reduces effective thickness
Petite device preferred for all implant patients undergoing stereotactic biopsy
Superficial lesions: manually advance needle until sampling well is just below skin before firing
Additional subcutaneous lidocaine pushes skin away, increasing skin-to-lesion distance

Lateral Arm Approach — Hologic Affirm

Horizontal needle approach enabling biopsy in thin breasts and challenging locations

Reduces failed stereotactic biopsy rate from ~13% to ~4%. Available as built-in (Affirm prone table) or accessory (upright unit).

Indications vs. Limitations

▼

Indications	Limitations
Thin breasts (min ~1 cm vs. ~2 cm standard)	Central lesions more difficult to access
Superficial and peripheral lesions	Larger breasts: 9 cm spinal needle may not reach deep targets
Lesions near chest wall	4th coordinate (Lat X) required on upright units — additional learning curve
Lesions obscured by lidocaine conventionally	Not yet widely adopted despite availability since 2007
Reduced radiation dose (fewer required views)	—

Standard vs. Lateral Arm — Key Difference

▼

Feature	Standard Vertical	Lateral Arm
Needle direction	Z-axis (into compression plane)	X-axis (parallel to compression paddle)
Min compressed thickness	~2.8 cm	~1.0 cm
Key coordinate	Z-depth	Lat X (manual insertion distance)
Breast thickness needed	In Z direction	Only marginally greater than needle width

Upright Unit — Step by Step

Najmi et al., UCLA; Hologic Affirm TRN-00576

▼

Confirm standard vertical approach is NOT amenable
Remove needle guide holder from upright unit
Install lateral arm compression paddle (system auto-targets for lateral approach)
Connect adaptor and needle guide to carriage; slide device mount onto lateral arm and lock
Install lateral arm stand on image receptor to elevate breast from detector
Position breast: align paddle EDGE with breast edge at entrance side (reduces coordinate error)
Acquire tomosynthesis scout
Click target — X, Y, Z, and Lat X coordinates auto-calculated and transmitted to control module
Note Lat X (circled red on screen) = manual insertion distance for biopsy device
Push motor-enable buttons to advance Z rail; adjust Z knob until all differential lines are green
Note safety margins to superior/inferior skin surfaces (blue circles on screen)
Attach sterile needle guide; load biopsy device
Administer local anesthesia with 18G 9 cm SPINAL NEEDLE (standard needles too short for lateral approach); use skin-to-needle-tip distance shown in green oval on screen
Manually insert biopsy device until X-stop (red arrow indicator) is reached
Verify needle location number matches X-stop value; lock carriage
Acquire pre-fire image; confirm needle at target
Fire device; acquire post-fire image; perform directional sampling
Place tissue marker; acquire post-marker images; remove device

AVOID sampling toward head or feet (superior/inferior). Risk of suctioning skin into trough at these margins.

Prone Table — Step by Step

▼

Unlock biopsy arm; swing to access breast from side
Position: CC view = lateral or medial access; ML or LM = superior or inferior access
Acquire tomosynthesis scout; click target (no separate Lat X coordinate needed)
Push motor-enable buttons — arm moves to Y and Z coordinates
Administer local anesthesia; manually advance needle to X coordinate
Confirm on pre-fire and post-fire images; perform biopsy; place marker

MRI-Guided Biopsy — Setup & Protocol

Patient preparation, grid targeting, obturator placement, and sampling

Indicated for lesions seen only on MRI. Requires dedicated biopsy coil, grid/paddle compression system, and MRI-compatible instrumentation.

Pre-Procedure Planning

▼

Review diagnostic MRI: confirm lesion present; determine approach (medial vs. lateral)
Choose approach = shortest distance from target to skin surface
Bilateral same-day biopsies: lateral approach for BOTH (medial inaccessible with lateral coil in place)
Verify MRI-compatible biopsy equipment and tissue marker for planned field strength (1.5T vs. 3T)
Confirm no MRI contraindications; verify eGFR if gadolinium concern

MRI Biopsy — Step by Step

▼

Position patient prone; ipsilateral breast in dedicated biopsy coil
Apply gentle compression paddle: stabilizes breast, reduces motion, allows adequate perfusion for enhancement
Administer IV gadolinium contrast
Acquire dynamic post-contrast sequences (3–5 phases)
Identify target; calculate grid coordinates (row, column, depth)
Select grid hole corresponding to target coordinates
Remove patient from bore; mark skin entry 'X' with sterile marker
Prepare skin; administer local anesthesia
Advance MRI-compatible obturator through grid hole to calculated depth
Return patient to bore; acquire post-obturator confirmation images
Confirm obturator position at or adjacent to target
Remove inner obturator; insert biopsy device through outer sheath
Fire device; obtain 6–10 samples (rotate between passes)
Place MRI-compatible tissue marker
Acquire post-marker MRI; remove device; apply pressure; dress wound
Obtain bilateral post-procedure mammograms (documents marker in 2 planes)
Radiology-pathology concordance review within 24–48 hours

If Target Not Visualized at Time of Biopsy

▼

Reduce compression — excessive compression may reduce perfusion and prevent enhancement
Obtain additional delayed sequences before cancelling
~40–50% of MRI-only lesions are benign; non-visualization may mean lesion resolved
Skin 'X' mark: if patient moved mid-procedure, misaligned X alerts to retarget
If still not visualized: cancel procedure; reassess with second-look US or short-interval MRI

MRI-Guided: Challenging Locations

Technical approaches for lesions at the margins of standard grid access

Superficial Lesions

▼

Use petite MRI biopsy device (smaller trough)
Target off-center in trough — place lesion near leading edge away from skin
Inject additional lidocaine into superficial tissue to displace skin from biopsy path

Near Implant / Anterior Lesions

▼

Displace implant posteriorly with compression before grid placement
Peri-implant lesions: place device adjacent to implant; directionally sample AWAY from implant
Anterior breast: add foam padding or saline bag between grid and anterior breast for adequate compression
Confirm adequate enhancement on post-obturator images before sampling

Far Posterolateral / Posteromedial Lesions

▼

Reposition BEFORE contrast administration. Repositioning post-contrast requires a second appointment with fresh contrast injection.

Posterolateral: prone oblique (elevate contralateral side); ipsilateral arm at side; remove table padding to maximize posterior tissue in coil; freehand angled technique to sample beyond grid edge
Posteromedial: prone oblique (elevate ipsilateral shoulder; roll breast toward contralateral coil) — allows medial breast access from lateral direction
If repositioning cannot access lesion: place MRI-compatible marker at obturator site for subsequent surgical localization

Wire Localization (WL)

Standard-of-care since 1976 — same-day surgery required

Lowest cost (~$20/device), proven reliability, MRI-compatible. Primary limitation: must be placed same day as surgery.

Wire Types & Introducers

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Wire	Features
Kopans spring hookwire	External needle removable post-deployment; most widely used
Homer J-wire	J-shaped tip; repositionable before deployment
Frank hookwire	Original design; 25G spinal needle preloaded
Pigtail wire	Pigtail anchor; various gauges and lengths

Introducers: sterile single-use, 16–20G, standard 10 cm (5–15 cm available)

Placement Technique — Step by Step

▼

Review imaging; confirm guidance modality (mammo, US, DBT, or MRI) and approach
Verify patient NPO per OR requirements (same-day surgery)
Position patient; administer local anesthesia
Advance introducer needle to target — tip 1–2 cm DEEP to lesion
Confirm needle position by imaging (spot views / real-time US / post-obturator MRI)
Advance internal flexible wire until midpoint (thickest part) is AT lesion; tip 1–2 cm beyond
Confirm wire position with orthogonal imaging
Remove external introducer needle — flexible wire remains
Coil externally protruding wire against skin; secure with tape and dressing
Obtain orthogonal mammographic views documenting wire location vs. lesion
Communicate to surgeon: depth from skin to lesion, wire type, mammographic documentation
Patient proceeds directly to OR

Outcomes & Limitations

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Metric	Data
Migration rate	0–1.8%
Positive margin rate	5.5–57% (higher for DCIS regardless of method)
Average surgical time	6–62 minutes
Device cost	~$20

Same-day surgery required — excludes first OR case; patient must be NPO
Wire migration: rare but reported — pneumothorax, mediastinal perforation, implant rupture
Axillary nodes: not preferred — arm movement may damage axillary vessels/brachial plexus
Higher patient anxiety vs. NWL devices; fasting + anxiety increases vasovagal risk

Bracketing (Multiple Wires)

▼

Indicated for nonpalpable lesions spanning 2.5–5.0 cm
No minimum distance between wires — multiple wires do not interfere (unlike NWL devices)
Pre-plan with surgeon for complex bracketing cases — discuss desired margins and cosmetic outcome
Obtain orthogonal views of all wires to document spatial relationship to lesion

Radioactive Seed Localization (RSL)

I-125 seed — NRC-regulated, 59.4-day half-life, superior scheduling flexibility

Decouples radiology and surgery schedules. Seeds effective for 90 days. Higher patient satisfaction than wire localization.

Device Specifications

▼

I-125-coated material in 4.5 × 0.8 mm titanium seed
Dose: 3.7–11.1 MBq (0.1–0.3 mCi) per seed
Half-life: 59.4 days; 27 keV gamma photon peak
Preloaded into sterile 18G needle with bone wax plug at tip
Standard needle: 10 cm; seeds effective for 90 days from preloading

Deployment — Step by Step

▼

If sentinel lymph node Tc-99 planned on same day: place seed first — GM meters cannot reliably differentiate I-125 from Tc-99.

Check seed needle with Geiger-Müller (GM) meter — confirm seed present
Advance needle to target under image guidance (US, mammo, or MRI)
Deploy: remove rubber stopper; simultaneously push internal stylet forward WHILE pulling needle hub backward
Rotate needle hub to ensure seed and bone wax fully expelled from tip
Withdraw needle; check biopsy site and needle with GM meter — confirm implantation
Obtain orthogonal imaging to document seed location
Bracketing: maintain ≥2 cm between seeds for differential intraoperative GM detection

Surgical Protocol & NRC Compliance

▼

Explantation standard: within 5 days (NRC license allows up to 14 days)
Surgeon uses intraoperative gamma probe to confirm activity and guide excision
Check surgical specimen AND cavity with gamma probe after excision
Seed returned to radiology for shielded decay and disposal per NRC license

4 NRC Reportable Medical Event Criteria: (1) wrong radionuclide; (2) seed in wrong patient; (3) wrong number of seeds; (4) failure to perform explantation surgery.

Outcomes

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Metric	Data
Migration rate	0.1–2%
Positive margin rate	5–32%
Cost	Comparable to WL after NRC infrastructure amortized
Patient preference	Superior to wire — lower anxiety, flexible scheduling

SAVI SCOUT (Radar Reflector)

FDA approved 2014 — electromagnetic reflector with audible/visual intraoperative feedback

12 mm infrared-activated reflector. 16G needle. FDA approved for breast AND axillary lymph node localization. 97% of patients would recommend.

Device & Deployment

▼

Two nitinol antennae attached by resistor — antennae anchor device and prevent migration
Housed in sterile 16G needle in 3 lengths: 5 cm, 7.5 cm, 10 cm
Approved depth: ≤6 cm from skin surface (measured supine by US)

Advance needle tip ~6 mm DISTAL to center of target
Deploy by withdrawal release: pull needle back while reflector deploys at center of target
Antennae self-expand to anchor device; confirm by orthogonal imaging
Bracketing: maintain ≥2 cm between devices

Intraoperative Detection & Limitations

▼

Handpiece transmits infrared signal; reflector responds with audible + visual feedback
Detection impaired: depth >6 cm, within hematoma, posterior to dense calcified mass
Signal interference: direct contact with electrocautery or older halogen OR lights
Contains nickel — contraindicated in documented nickel allergy
MRI: minimal artifact at 1.5T and 3T (advantage over Magseed and RFID)

Outcomes

▼

Metric	Data
Migration rate	4.5–7.0% (highest of all NWL — mostly from post-procedural hematoma)
Positive margin rate	0–16.8%
Device cost	~$450 (plus console and handpiece)
MRI artifact	Minimal at 1.5T and 3T

Magseed (Magnetic Seed)

FDA approved 2016 — paramagnetic seed with Sentimag numerical + audible detection

5 × 1 mm paramagnetic iron oxide and stainless steel. 18G deployment needle. Does not interfere with electrocautery.

Device & Deployment

▼

Non-radioactive; 5 mm × 1 mm cylindrical; preloaded in sterile 18G stainless steel needle
Bone wax plug stabilizes seed before deployment
Manufacturer-specified sensing depth: ~4 cm

Advance needle tip to center of target
Deploy: advance steel obturator forward while pulling needle backward
Confirm placement by orthogonal imaging
Bracketing: maintain ≥2 cm between seeds for independent detection

Sentimag Detection & Key Limitation

▼

Sentimag probe generates alternating magnetic field; audio frequency + numerical value increase near seed
Non-ferromagnetic intraoperative instruments required to eliminate magnetic interference

Largest MRI artifact (~4 cm) of all NWL devices. Avoid in patients requiring post-treatment MRI evaluation of residual disease.

Outcomes

▼

Metric	Data
Migration rate	0–4.5%
Positive margin rate	9–22%
Device cost	~$400
MRI artifact	~4 cm (largest of all NWL)

RFID Tag — Hologic LOCalizer

FDA approved for long-term placement — unique ID enables multi-tag differentiation

11 × 2 mm RFID tag with unique identification number. 12G applicator. FDA approved for long-term placement (>30 days). Unique ID differentiates multiple tags in same breast.

Device & Deployment

▼

Ferrite rod + copper + microprocessor in glass casing with polypropylene antimigratory sheath
Preloaded in sterile 12G needle; unique RFID identification number per tag
May require small skin incision — 12G is the largest of all NWL applicators

Advance needle tip to center of target
Deploy: advance steel obturator pushing tag from needle tip
Confirm placement by orthogonal imaging
Critical: if two tags placed <1.8 cm apart, unique IDs will NOT appear on reader — use wire localization for close-proximity bracketing

Intraoperative Detection & Limitations

▼

Handheld reader: audible signal + visual distance indicator (up to 60 mm)
Displays unique tag ID — critical when multiple tags present
Glass casing may fracture during surgical excision — alert surgical team
12G applicator difficult in dense breast tissue

MRI artifact 2–5 cm. Avoid in patients requiring post-NAC MRI evaluation of residual disease.

Outcomes

▼

Metric	Data
Migration rate	0–0.6% (lowest of all NWL devices)
Positive margin rate	0–27%
Device cost	~$550
MRI artifact	2–5 cm

Localization Device Comparison

Side-by-side comparison of all preoperative localization methods

No statistically significant differences in overall surgical outcomes between wire and non-wire localization. Choice should be driven by institutional factors, multidisciplinary input, and patient preference.

Feature	Wire	RSL (I-125)	SAVI SCOUT	Magseed	RFID
Gauge	16–20G	18G	16G	18G	12G
Decouples scheduling	✗ Same-day only	✓ ≤14 days	✓	✓	✓ Long-term
MRI artifact	None	None	Minimal	~4 cm ⚠	2–5 cm ⚠
Migration rate	0–1.8%	0.1–2%	4.5–7.0%	0–4.5%	0–0.6%
Cost/device	~$20	Low after setup	~$450	~$400	~$550
Regulatory	None	NRC license required	None	None	None
Axillary nodes	Limited	Not standard	FDA approved	Yes	Yes
Nickel allergy concern	No	No	⚠ YES	No	No
Electrocautery interference	No	No	⚠ Older halogen	No	No
Patient satisfaction	Lower	Higher	97% recommend	Higher	Higher

Breast Cryoablation — Overview

Minimally invasive ablation for small breast cancers — current evidence and patient selection

✔ FDA-Approved 2025 (IceCure ProSense — Breast Cancer) ▲ Other Devices: Investigational First FDA-approved cryoablation device specifically for breast cancer treatment (not just fibroadenomas)

IceCure ProSense — FDA Approved 2025: The IceCure ProSense system received FDA approval for breast cancer treatment in 2025 — the first FDA approval of a cryoablation device specifically for breast cancer (prior approvals covered fibroadenomas only). This changes the status from investigational to FDA-approved for selected patients meeting criteria similar to the FROST and ICE3 trial eligibility (women ≥50–60, unifocal US-visible HR+/HER2- grade 1–2 IDC ≤1.5 cm, node-negative).

Breast cryoablation uses percutaneously placed cryoprobes to freeze and destroy breast tissue using liquid nitrogen or argon gas (freeze cycle) and helium gas (thaw cycle). Ice ball formation destroys cells through intracellular ice crystal formation, membrane disruption, osmotic injury, and vascular stasis. Cryoablation also induces immunogenic cell death — releasing tumor antigens and pro-inflammatory cytokines that can activate innate and adaptive immune responses.

Technical Parameters

Parameter	Details
Probe	Single cryoprobe (FROST protocol); 17G ProSense (IceCure Medical, liquid nitrogen)
Guidance	Real-time ultrasound (primary); CT or MRI feasible for special cases
Freeze cycles	Double freeze-thaw-freeze cycle; typically 8–10 min per freeze cycle
Ice ball monitoring	Ultrasound — hyperechoic leading edge visualized in real time
Target margin	Ice ball must extend ≥1 cm beyond tumor edge on all sides
Anesthesia	Local anesthesia ± IV sedation; outpatient procedure
Confirmatory biopsy	Post-ablation core biopsy mandatory (FROST: 6-month biopsy); confirms complete ablation
Recovery	Return to activity within 24–48 hours; no incision, no drain, no wound care

Patient Selection Criteria (FROST / ICE3 / FDA Parameters)

Age: ≥50 (Stratum 1: ≥70; Stratum 2: 50–69 with radiation); ICE3 required ≥60
Histology: Biopsy-proven invasive ductal carcinoma (IDC) — non-lobular histology
Receptor status: HR+ (ER/PR+) / HER2-negative
Grade: Grade 1–2 (well to moderately differentiated)
Tumor size: Unifocal, US-visible, ≤1.5 cm (FROST median 9mm; ICE3 ≤1.5 cm)
Nodal status: Node-negative (cN0) on clinical imaging
DCIS component: No significant intraductal (DCIS) component on core needle biopsy
Multifocality: Unifocal disease only; no multicentric cancer
Ultrasound visibility required for real-time guidance

Contraindications

Multifocal or multicentric disease
Significant DCIS component
Lobular histology (diffuse growth pattern, difficult to define margins)
Tumor not visible on ultrasound
HR-negative or HER2-positive tumor
Node-positive disease (cN1+)
Locally advanced disease (T3/T4)
Prior radiation to ipsilateral breast

Ablation vs Surgery — Decision Framework

Current evidence synthesis for cryoablation in clinical practice

2025 Status Update: IceCure ProSense system received FDA approval for breast cancer treatment in 2025. FROST Phase II 6-year data (Holmes et al. Ann Surg Oncol. 2026) and ICE3 5-year data (Fine et al. 2024) now provide mature outcomes supporting selected use. Strict patient selection remains critical — trial-ineligible patients had 18.2% IBTR at 3 years (Oueidat et al. AJR 2024).

Ideal Candidate Criteria

Age: ≥50–60 (strongest data for ≥70 in FROST Stratum 1)
Histology: Unifocal invasive ductal carcinoma (IDC) — non-lobular
Receptor: HR+ (ER/PR+) / HER2-negative, grade 1–2
Size: ≤1.5 cm, US-visible (median tumor size in FROST: 9 mm)
Nodes: Node-negative (cN0) by clinical imaging
DCIS: No significant intraductal component on core biopsy
Genetics: No known BRCA1/2 pathogenic variant
Prior Tx: No prior ipsilateral breast radiation

Summary Evidence Table

Parameter	Evidence	Current Status
Complete ablation (FROST)	82/83 patients (99%); Phase II	Established feasibility
Complete ablation (ACOSOG Z1072)	75.9% overall; 92% within ablation zone	Size-dependent; excludes >25% DCIS
5-yr IBTR — FROST overall	3.64% (Holmes et al. 2026)	Phase II; no randomized comparison
5-yr IBTR — FROST Stratum 1 (≥70, ET only)	2.08%	Best outcomes subgroup
5-yr IBTR — FROST Stratum 2 (50–69, ET+RT)	5.80%	Higher; RT required in this group
5-yr IBTR — ICE3 (Fine 2024)	4.3%; n=194, age ≥60	Phase II; completed
Trial-ineligible patients (real-world)	18.2% IBTR at 3 years (Oueidat 2024)	Critical — strict selection required
FDA approval for breast cancer Tx	IceCure ProSense — FDA approved 2025	First-ever approval for cancer (not just FA)

Head-to-Head: Cryoablation vs Lumpectomy + RT

Factor	Cryoablation	Lumpectomy + RT
Procedure time	30–60 min (outpatient)	60–90 min (OR) + weeks of RT
Recovery	24–48 hours; no wound, no drain	2–4 weeks post-op + 3–6 weeks RT
5-yr local recurrence	3.64% overall / 2.08% (age ≥70, FROST)	~1–2% at 5 years (standard of care)
Margin confirmation	Not possible (ablation zone, no specimen)	Pathologic margins confirmed in specimen
Cosmesis	Excellent (no incision); 95–98% satisfaction (ICE3)	Good to excellent (breast-conserving)
Cost (Khan 2023)	$2,221.70 mean procedure cost	$16,896.50 mean procedure cost
FDA status (breast cancer)	FDA-approved 2025 (IceCure ProSense)	Standard of care

Post-Ablation Follow-Up Protocol

FROST protocol: Mandatory core biopsy at 6 months + regular clinical exams and imaging
Khan et al.: Mammogram + US at 6 months; MRI at baseline then annually
CEM: Emerging as a practical MRI alternative for post-ablation surveillance

Expected Post-Ablation Imaging Findings (Benign)

Normal findings after cryoablation: Rim enhancement, decreased lesion size, and evolving parenchymal changes on MRI or CEM are expected and do not indicate recurrence. These typically evolve over 12–24 months.

Findings requiring further evaluation + biopsy: Persistent or new focal enhancement, increasing mass size, or discordant imaging findings should prompt further evaluation and biopsy.

Cryoablation Clinical Trials

Key trials for breast cancer, palliative/metastatic, and immunotherapy indications

Breast Cancer — Definitive Cryoablation

FROST

FROST — Phase II Multicenter Cryoablation Study

NCT01992250 — Holmes et al. Ann Surg Oncol. 2026

Phase 2Completed (6-yr data)N = 83

Women ≥50 with stage I HR+/HER2- node-negative IDC. Single cryoprobe, US-guided. Post-ablation core biopsy at 6 months. Stratum 1 (≥70, endocrine therapy only); Stratum 2 (50–69, endocrine therapy + radiation). Median tumor size 9 mm.

Positive — 6-Year Outcomes — Complete ablation in 82/83 patients. 5-yr IBTR overall: 3.64%. Stratum 1 (≥70, ET only): 2.08%; Stratum 2 (50–69, ET+RT): 5.80%. No serious adverse events.

Holmes DR et al. Ann Surg Oncol. 2026; NCT01992250.

ICE3

ICE3 — Cryoablation as Definitive Treatment Without Surgery

Fine et al. Ann Surg Oncol. 2024

Phase 2Completed (5-yr data)N = 194

194 women ≥60 with unifocal US-visible IDC ≤1.5 cm, grade 1–2, HR+/HER2-. Cryoablation as definitive treatment (no surgical excision) + standard adjuvant endocrine therapy.

Positive — 5-Year Data — 5-yr IBTR: 4.3%. Breast cancer-specific survival: 96.7%. >95% of patients and 98% of physicians satisfied with cosmesis. No serious device-related adverse events.

Fine RE et al. Ann Surg Oncol. 2024.

ACOSOG Z1072

Alliance/ACOSOG Z1072 — Ablation Before Surgical Resection

Simmons et al. Ann Surg Oncol. 2016

Phase 2Completed

Unifocal IDC ≤2 cm with <25% intraductal component. US-guided cryoablation followed by standard surgical resection.

Positive — Feasibility Established — Complete ablation: 75.9%. Within ablation zone only: 92%. MRI NPV for residual disease: 81.2%.

Simmons RM et al. Ann Surg Oncol. 2016.

Khan et al.

Khan — Office-Based Cryoablation for IDC

Ann Surg Oncol. 2023

ProspectiveCompletedN = 32

ER/PR+/HER2- IDC ≤1.5 cm treated with office-based cryoablation. Assessed oncologic outcomes and cost-effectiveness.

Positive — Zero residual or recurrent disease at ablation site among 20 patients with ≥2 years follow-up. Mean cost: $2,221.70 (cryo) vs. $16,896.50 (surgery), p<0.0001.

Khan SA et al. Ann Surg Oncol. 2023.

Oueidat et al.

Oueidat — Real-World Outcomes in Trial-Ineligible Patients

AJR. 2024 — Multi-institutional

RetrospectiveCompleted

Multi-institutional retrospective of patients treated with cryoablation who were INELIGIBLE for clinical trials.

Cautionary — Cumulative IBTR: 18.2% at 3 years in trial-ineligible patients. Underscores the critical importance of strict patient selection.

Oueidat K et al. AJR. 2024.

Palliative & Metastatic Breast Cancer

Beji 2018

Beji — Cryoablation for Stable Metastatic Breast Cancer

Br J Radiol. 2018

ProspectiveCompletedN = 17

Positive — Complete regression in 15/17 patients. Durable pain relief in all 5 painful masses treated.

Beji H et al. Br J Radiol. 2018.

Chi 2024

Chi — Cryoablation of Metastases in Metastatic Breast Cancer

J Clin Oncol. 2024

Phase 2CompletedN = 37

Positive — Median PFS: 7.1 months. Median time to next treatment: 14 months. Local recurrence within ablation zone: 4%.

Chi JT et al. J Clin Oncol. 2024.

Cryoablation — Fibroadenoma

FDA-approved treatment for benign breast fibroadenomas — guidelines, trials, and selection criteria

✔ FDA-Approved (Fibroadenoma) Established standard of care for symptomatic or bothersome biopsy-proven fibroadenomas <3 cm

ASBrS/SBI 2025 Guidelines (Rosenberger et al. JAMA Surgery 2025): Endorse cryoablation for biopsy-proven fibroadenomas <3.0 cm. Strict radiologic-pathologic concordance required. Exclude phyllodes tumor, atypia, and malignancy on core needle biopsy before proceeding.

Patient Selection Criteria

Biopsy-proven fibroadenoma (core needle biopsy) — strict rad-path concordance required
Lesion size <3.0 cm (ASBrS/SBI 2025 cutoff)
Ultrasound-visible lesion (required for real-time guidance)
Symptomatic (pain, cosmetic concern, anxiety) or patient preference to avoid open excision
Exclude: phyllodes tumor, atypia, or malignancy on CNB

Trial Data

Filipov 2026

Filipov — Liquid Nitrogen Cryoablation, n=78

PLoS One. 2026

ProspectiveCompletedN = 78

Median volume reduction 92.9% at 12 months. Adverse event rate 0.81%. Largest contemporary prospective series demonstrating excellent efficacy.

Filipov O et al. PLoS One. 2026.

Kaufman 2004

Kaufman — Pivotal Multicenter Studies Supporting FDA Clearance

Am J Surg. 2004 / J Am Coll Surg. 2004

Volume reduction 87.3–89%. 75% of fibroadenomas became nonpalpable. Patient satisfaction good/excellent: 91–92%. Supported FDA clearance.

Kaufman CS et al. Am J Surg. 2004; J Am Coll Surg. 2004.

Economic Case (Rath et al. World J Surg. 2025): Over 81,000 excisional breast biopsies are performed annually in the United States at a conservative estimated cost of $662 million. Widespread adoption of cryoablation for eligible fibroadenomas offers substantial cost savings and reduced patient morbidity.

Cryoablation + Immunotherapy

Immunogenic cell death, abscopal effect, and combination checkpoint inhibition trials

Rationale: Unlike surgical excision, cryoablation induces immunogenic cell death through necrosis and osmotic injury, releasing tumor antigens and pro-inflammatory cytokines that activate innate and adaptive immune responses. This mechanism may be synergistic with immune checkpoint inhibitors — potentially converting a locally treated tumor into an in situ tumor vaccine.

Mechanism of Immunogenic Cell Death

Cell death via intracellular ice crystal formation + osmotic injury — necrotic, immunogenic (contrast with apoptosis, which is immunologically silent)
Tumor cell necrosis releases DAMPs, tumor antigens, and pro-inflammatory cytokines (IL-1β, HMGB1, ATP)
Activates innate immune cells (NK cells, dendritic cells) and initiates antigen cross-presentation to T cells
May prime systemic anti-tumor immune response capable of targeting distant metastases (abscopal effect)

Phase II Clinical Trial — NCT03546686

NCT03546686

Perioperative Cryoablation + Ipilimumab + Nivolumab for TNBC

Phase II — HR-negative/HER2-negative TNBC

Phase 2Ongoing

Population: HR-negative/HER2-negative early-stage TNBC or residual TNBC after neoadjuvant chemotherapy.

Treatment: Perioperative cryoablation → Ipilimumab 1 mg/kg IV + Nivolumab 240 mg IV → standard surgical excision → adjuvant nivolumab or pembrolizumab ± capecitabine/olaparib.

Primary endpoint: 3-year event-free survival (EFS).

Preliminary Positive — Safe combination with no unexpected toxicities. Robust intra-tumoral and systemic immune responses observed (increased TILs, systemic T-cell activation). Full 3-year EFS data pending.

NCT03546686; preliminary data reported 2023–2024.

Current Status: Cryo + immunotherapy combinations are investigational and should only be pursued within clinical trials. NCT03546686 is the primary US phase II trial. Not currently part of NCCN or standard institutional guidelines.

FES PET/CT — Overview & Indications

¹⁸F-Fluoroestradiol (Cerianna) · FDA-approved 2020 · Functional ER imaging adjunct to biopsy

What it is: 16α-[¹⁸F]fluoro-17β-estradiol (FES) is a radiolabeled estrogen analogue PET tracer that binds the estrogen receptor (ER) in the nucleus of ER-expressing cells. It provides whole-body, noninvasive, in vivo assessment of functional ER expression — a complement to IHC that addresses sampling error, heterogeneity, and inaccessible biopsy sites. FDA-approved May 2020 (US); 2016 (France, trade name EstroTep). Marketed in the US as Cerianna (GE Healthcare). Unlike FDG, FES does not localize to inflammation, reactive nodes, or degenerative processes.

SNMMI Appropriate Use Criteria (2023)

All four current Appropriate indications target patients with known recurrent or metastatic ER+ breast cancer. Primary staging, routine T/N staging, and response assessment are Rarely Appropriate.

Appropriateness	Clinical Scenario	Score (1–9)
Appropriate	ER status assessment when biopsy is unfavorable or nondiagnostic	8
	ER detection when prior imaging findings are equivocal or suspicious	8
	Initial diagnosis of metastatic disease — for consideration of endocrine therapy	8
	Progression of metastatic disease — for consideration of 2nd-line endocrine therapy	8
May Be Appropriate	Unknown primary when biopsy not feasible	5
	Routine staging of extra-axillary nodes and distant metastases	5
	Staging invasive lobular carcinoma (ILC) or low-grade IDC	5
	ER status in lieu of biopsy for accessible lesions	5
	Lesion detection in suspected/known recurrent or metastatic disease	5
Rarely Appropriate	Diagnosing primary breast cancer	2
	Routine T-staging of primary tumor	1
	Routine staging of axillary nodes	3
	Initial diagnosis of primary cancer — for endocrine therapy	1
	Measuring response to therapy	1

2023 NCCN update: FES PET/CT added as "may be useful in certain circumstances" for Stage IV or recurrent ER+ disease. NCCN does not position FES as an alternative to FDG PET/CT — they perform different functions (FDG: disease identification; FES: disease characterization). Some insurers will only approve one PET scan per patient; document the distinct clinical indication clearly.

Drug Interactions — Must Withhold Before Imaging

ER-blocking drugs competitively inhibit FES uptake and cause false-negative results

Critical: The FDA label requires washout of at least 5 biological half-lives before FES imaging for any drug that binds the ER. This is the most important pre-scan checklist item. Whether these washout periods are truly sufficient — particularly for fulvestrant, which degrades the ER itself — remains an area of active research; tumor drug concentrations may outlast plasma levels, and tamoxifen metabolites take 4–6 weeks to reach steady-state.

Drug	Class	FDA-Required Washout	Clinical Notes
Elacestrant	Oral SERD	≥ 11 days	5 × t½ (~2.2 days)
Tamoxifen	SERM	≥ 8 weeks	Active metabolites (endoxifen, 4-OH-tamoxifen) have prolonged half-lives; full washout extended well beyond parent drug clearance
Fulvestrant	IM SERD	≥ 28 weeks	t½ ~40 days; also degrades ER (not just blocks it) — FES imaging during fulvestrant therapy is essentially infeasible in routine clinical practice. Oncologists are often reluctant to withhold therapy this long
Aromatase inhibitors letrozole, anastrozole, exemestane	AI	No washout required	Work peripherally (suppress estrogen synthesis); do not bind ER directly. FES imaging proceeds normally during AI therapy
CDK4/6 inhibitors palbociclib, ribociclib, abemaciclib	CDKi	No washout required	Do not interact with ER. FES imaging proceeds normally

Practical note: If a patient cannot complete the required washout — especially the 28-week fulvestrant holdout — FES PET/CT cannot be meaningfully interpreted. Discuss timing with the referring oncologist before scheduling. Patients who are off ER-blocking therapy are the ideal candidates. Aromatase inhibitor-treated patients can be imaged without any hold.

Imaging Protocol & Normal Biodistribution

Patient preparation, administration, and expected physiologic distribution

Protocol

Parameter	Details
Dose	222 MBq (6 mCi); acceptable range 111–222 MBq (3–6 mCi)
Administration	IV push over 1–2 min via syringe pump + ≥10 mL normal saline flush
Uptake time	60–80 min post-injection (feasible as early as 20 min to limit bowel tracer accumulation)
Coverage	Vertex/skull base to mid-thigh; arms above head, supine
Patient prep	Hydrate well; void immediately before scanning to reduce bladder activity adjacent to pelvic structures; no fasting or dietary restrictions required; no pregnancy test unless childbearing potential
SUV windowing	Default: 0–5. Increase to 0–20 for areas adjacent to liver/bowel. Narrow to 0–2.5 for precise assessment of hepatic/abdominal lesions
Radiation dose	~4.9 mSv effective dose from 222 MBq; critical organs: liver, gallbladder, uterus

Normal Biodistribution

Expected High Uptake (Normal)

Liver — highest background; the radiotracer's critical organ
Biliary system / common bile duct
Small bowel — reabsorbed radiolabeled metabolites via enterohepatic circulation
Kidneys / ureters / bladder — excretion
Uterus — high ER expression; serves as internal control confirming adequate FES tissue binding
Injection site vein — residual tracer in draining vein is expected

NOT Expected (Unlike FDG)

Reactive / inflammatory lymph nodes
Stimulated marrow / marrow repopulation after G-CSF
Degenerative osseous disease
Sites of active infection or inflammation
Brain parenchyma (no physiologic uptake → brain metastases are conspicuous on FES)
Brown fat / symmetric mediastinal/hilar uptake

Uterine uptake as internal QC: Confirmed uterine FES uptake in a patient with a uterus validates that the radiopharmaceutical is binding ER-expressing tissue appropriately. Absence of uterine uptake in a pre/perimenopausal patient should raise concern about ER-blocking drug effect.

Image Interpretation

FES positivity thresholds, windowing strategy, and diagnostic performance

Finding	Threshold / Definition	Implication
FES-positive lesion	SUV_max ≥ 1.5 or qualitatively above local background and blood pool	Functionally ER-positive disease. Predicts likelihood of response to endocrine-targeted therapy
FES-negative lesion	SUV_max < 1.5 / at or below local and blood pool background	ER-negative, functionally ER-negative, or endocrine-refractory. In landmark data, 0/15 patients with all-site SUV <1.5 responded to endocrine therapy
Hepatic & bowel lesions	High physiologic liver background may mask ER+ disease; lesional SUV may be below hepatic parenchyma even at SUV >1.5	Greatest limitation of FES PET. Correlate with MRI or consider biopsy. Window images down to 0–2.5 and consider delayed imaging or early acquisition before bowel excretion

Sensitivity & specificity vs. IHC: Meta-analyses report sensitivity 71–95%, specificity 80–98% for ER-positive lesions. A 2022 prospective study (n=200) found sensitivity 95%, specificity 80%, PPV 93%, NPV 85% using IHC as the reference standard. FES specificity for ER-positive disease is ~98% in one large meta-analysis.

Factors Affecting FES Uptake

Factor	Effect	Note
SHBG (sex hormone-binding globulin)	Inversely associated — higher SHBG → lower FES SUV	~45% of circulating FES is SHBG-bound; the only independent predictor of lean body mass–adjusted FES uptake in multivariate analysis
Endogenous estradiol (premenopausal)	No significant effect on diagnostic accuracy	Physiologic estrogen levels do not interfere with FES uptake. FES can be used in pre- and postmenopausal women and in men
ER-blocking drugs	Markedly reduces or eliminates FES uptake → false-negative	See Drug Interactions section — the single most important pre-scan check
Tumor size	Small lesions (<1 cm) may fall below PET resolution threshold	Partial volume effect limits sensitivity for sub-centimeter disease; uptake may not exceed background

False Positives & False Negatives

Pitfalls in FES PET/CT interpretation

Category	Entity	Mechanism / Practical Note
False Positive	Uterine fibroids / endometrium	ER-expressing benign tissue; uterus is expected to be FES-avid — do not call uterine uptake pathologic in patients with a uterus
	Other ER+ malignancies (uterine, ovarian, endometrial)	May produce unexpected FES-avid lesions outside of breast cancer distribution; clinical correlation required in patients with dual malignancies
	Meningiomas	May show FES uptake; absence of physiologic brain uptake makes these conspicuous — do not mistake for intracranial metastasis. Brain MRI recommended for clarification
	Post-radiation pulmonary/nodal changes	FES uptake in irradiated lung seen in >50% of cases in one series. Draining lymph nodes of irradiated fields may also be FES-avid. Likely reflects vascular permeability/extravasation rather than ER binding — correlate with timing of radiation and FDG PET
False Negative	Liver metastases	High hepatic physiologic background; even large lesions may have a SUV below hepatic parenchyma. The greatest limitation of FES PET — do not exclude liver metastases based on negative FES scan alone. Correlate with MRI or CECT
	Peritoneal / bowel metastases	High bowel background from biliary/enteric excretion of radiolabeled metabolites limits detection of peritoneal disease close to bowel
	Small lesions (<1 cm)	Below PET resolution threshold; partial volume averaging reduces apparent SUV. May still show uptake qualitatively above background in some cases
	Truly ER-negative / ER-converted disease	Triple-negative breast cancer, and ER+ primaries that have lost ER expression at metastatic sites, will not show FES uptake — this is the expected and meaningful finding, not a scan failure. ER conversion occurs in 8–33% of patients over disease course

Discordant FES-negative / IHC-positive results: A negative FES scan in a patient with IHC-positive disease should not automatically override endocrine therapy decisions. Biopsy or additional imaging should be considered. However, FES-negativity in IHC-positive tumors is a strong predictor of endocrine therapy nonresponse and carries significant clinical meaning.

Clinical Applications

ILC staging, ER heterogeneity, FDG complementarity

Invasive Lobular Carcinoma (ILC)

ILC is nearly always ER+ (>90%) but is poorly detected by FDG PET due to low cellularity and glucose metabolism. FES PET/CT demonstrates particular promise:

Changed clinical stage in 18% of ILC patients in a prospective study
Detected metastases not seen on standard imaging in 24% of patients
Head-to-head: FES detected 254 vs. 111 total lesions compared to FDG PET in one ILC series (71% of patients)
ILC metastasizes to unusual locations (peritoneum, GI tract, bone marrow) where FDG sensitivity is lower; FES can identify these ER+ sites
SNMMI rates ILC staging as "May Be Appropriate" (score 5)

ER Heterogeneity & Endocrine Therapy Selection

15–45% of metastatic breast cancer patients have FES-heterogeneous disease (a mix of FES+ and FES− sites at a single time point). Temporal ER conversion (ER loss at a previously positive site) occurs in 8–33% over the disease course.

Patients with 100% FES-avid disease had longest PFS on endocrine therapy combined with CDK4/6 inhibition (73 wk vs. 20 wk for FES-heterogeneous and 15 wk for 100% FES-negative)
FES-heterogeneous patients treated with endocrine therapy had shorter PFS than those treated with chemotherapy (median 4.6 vs. 7.1 months in one retrospective study)
FES negativity in an IHC-positive tumor: zero of 15 patients with all-site SUV <1.5 responded to endocrine therapy in a landmark study — the strongest negative predictive signal in the literature

FES + FDG: Complementary Tracers

FDG and FES image different aspects of disease biology and are best viewed as complementary. Across four studies, FES PET led to treatment change in 50% of patients with equivocal imaging findings.

FDG+, FES+: ER+ metabolically active metastasis — supports endocrine therapy + CDK inhibition
FDG+, FES−: Metabolically active but ER-negative or functionally ER-negative — endocrine therapy less likely to succeed; biopsy recommended; may support chemotherapy-based regimen
FDG−, FES+: Indolent ER+ disease (e.g., sclerotic bone mets) — supports endocrine therapy; FDG alone would have underdetected these
Both negative: Broad differential — benign finding vs. non-ER, non-FDG-avid disease; biopsy if clinically indicated

Dual-tracer imaging on separate days is the current standard (¹⁸F t½ = 110 min — next-day imaging is sufficient). Research protocols using long axial field-of-view (LAFOV) PET scanners to acquire both tracers in a single session are in development.

Safety, Adverse Reactions & Precautions

Excellent safety profile — key precautions are clinical, not toxicologic

Category	Details
Adverse reactions	Extremely rare: in 1,207 patients studied, only injection-site pain and dysgeusia (altered taste) were reported. In a prospective safety study (n=90), procedural pain occurred in 10% of patients — attributable to mechanical needle insertion, not the radiopharmaceutical. Only 1 patient (1%) had a drug-related adverse event (injection site pain). No serious adverse events recorded in any study.
Contraindications	None listed in FDA prescribing information
Not a biopsy substitute	FES PET should not replace biopsy when biopsy is indicated. A negative FES scan should not override clinical or pathologic evidence supporting endocrine therapy. Biopsy confirmation is still recommended when FES PET results will change management.
Radiation safety	~4.9 mSv effective dose from 222 MBq (6 mCi). Standard radiation safety precautions apply. Critical organs: liver, gallbladder, uterus.
Pregnancy	No human or animal studies available. Confirm negative pregnancy test before administration in women of childbearing potential. All radiopharmaceuticals carry potential for fetal harm.
Lactation	Interrupt breastfeeding for at least 4 hours after administration (per Cerianna prescribing information). NRC guidance: pumped milk from mothers given most radiopharmaceuticals can be stored safely for 10 physical half-lives of the radionuclide (¹⁸F t½ = 110 min → ~18 hours for 99.999% radioactive decay). Some experts recommend 12-hour avoidance of close infant contact after injection, though this is not specifically stated in the Cerianna label.

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