Reproducibility and intratumoral heterogeneity of the PAM50 breast cancer assay.

BACKGROUND: The PAM50 assay is used routinely in clinical practice to determine breast cancer prognosis and management; however, research assessing how technical variation and intratumoral heterogeneity contribute to misclassification and reproducibility of these tests is limited. METHODS: We evaluated the impact of intratumoral heterogeneity on the reproducibility of results for the PAM50 assay by testing RNA extracted from formalin-fixed paraffin embedded breast cancer blocks sampled at distinct spatial locations. Samples were classified according to intrinsic subtype (Luminal A, Luminal B, HER2-enriched, Basal-like, or Normal-like) and risk of recurrence with proliferation score (ROR-P, high, medium, or low). Intratumoral heterogeneity and technical reproducibility (replicate assays on the same RNA) were assessed as percent categorical agreement between paired intratumoral and replicate samples. Euclidean distances between samples, calculated across the PAM50 genes and the ROR-P score, were compared for concordant vs. discordant samples. RESULTS: Technical replicates (N = 144) achieved 93% agreement for ROR-P group and 90% agreement on PAM50 subtype. For spatially distinct biological replicates (N = 40 intratumoral replicates), agreement was lower (81% for ROR-P and 76% for PAM50 subtype). The Euclidean distances between discordant technical replicates were bimodal, with discordant samples showing higher Euclidian distance and biologic heterogeneity. CONCLUSION: The PAM50 assay achieved very high technical reproducibility for breast cancer subtyping and ROR-P, but intratumoral heterogeneity is revealed by the assay in a small proportion of cases.

Pathological measurement and staging of residual breast cancer after neoadjuvant chemotherapy.

AIMS: The 8th Edition of the American Joint Committee on Cancer Staging System (yAJCC) excludes treatment-related fibrosis from the measurement of residual tumour after neoadjuvant chemotherapy (NAC) for breast cancer. The impact of the 8th Ed. yAJCC on post-NAC pathologic staging was examined in 188 breast cancer specimens from 183 patients with measurable residual tumour. METHODS: Tumour size, ypT, and ypN categories were reassessed with the current yACC criteria and compared to the original pathology reports. Histological patterns of response in the breast were categorised as concentric or scattered. RESULTS: The reassessed breast tumour size or ypT category differed from the original report in 101 (53.7%) cases. Changes in the ypT and/or ypN category resulted in downstaging of 45/185 (24.3%). A smaller reassessed tumour size or lower ypT category occurred more often in hormone receptor-positive/HER2-negative (HR+/HER2-) (68.3%) and HER2-positive (HER2+) tumours (74.0%) than triple-negative breast cancer (TNBC) (37.5%) (P < 0.001). A scattered pattern of response was more frequent in HR+/HER2- (54.9%) and HER2+ (66.0%) tumours than TNBC (35.7%) (P = 0.006). Changes in size, ypT, or multifocality based on the 8th Ed. yAJCC criteria were more frequent in tumours with a scattered pattern of response (P < 0.001). CONCLUSION: Strict adherence to yAJCC criteria for measurement of the residual breast tumour after NAC resulted in smaller tumour size, lower ypT category, lower yAJCC stage, and more frequent classification of residual tumour as multifocal. Downstaging based on 8th Ed. yAJCC criteria was associated with tumour subtype and histological pattern of response.

High-risk and selected benign breast lesions diagnosed on core needle biopsy: Evidence for and against immediate surgical excision.

The vast majority of image-detected breast abnormalities are diagnosed by percutaneous core needle biopsy (CNB) in contemporary practice. For frankly malignant lesions diagnosed by CNB, the standard practice of excision and multimodality therapy have been well-defined. However, for high-risk and selected benign lesions diagnosed by CNB, there is less consensus on optimal patient management and the need for immediate surgical excision. Here we outline the arguments for and against the practice of routine surgical excision of commonly encountered high-risk and selected benign breast lesions diagnosed by CNB. The entities reviewed include atypical ductal hyperplasia, atypical lobular hyperplasia, lobular carcinoma in situ, intraductal papillomas, and radial scars. The data in the peer-reviewed literature confirm the benefits of a patient-centered, multidisciplinary approach that moves away from the reflexive "yes" or "no" for routine excision for a given pathologic diagnosis.

Protein-based immune profiles of basal-like vs. luminal breast cancers.

Tumor-infiltrating lymphocytes play an important, but incompletely understood role in chemotherapy response and prognosis. In breast cancer, there appear to be distinct immune responses by subtype, but most studies have used limited numbers of protein markers or bulk sequencing of RNA to characterize immune response, in which spatial organization cannot be assessed. To identify immune phenotypes of Basal-like vs. Luminal breast cancer we used the GeoMx® (NanoString) platform to perform digital spatial profiling of immune-related proteins in tumor whole sections and tissue microarrays (TMA). Visualization of CD45, CD68, or pan-Cytokeratin by immunofluorescence was used to select regions of interest in formalin-fixed paraffin embedded tissue sections. Forty-four antibodies representing stromal markers and multiple immune cell types were applied to quantify the tumor microenvironment. In whole tumor slides, immune hot spots (CD45+) had increased expression of many immune markers, suggesting a diverse and robust immune response. In epithelium-enriched areas, immune signals were also detectable and varied by subtype, with regulatory T-cell (Treg) markers (CD4, CD25, and FOXP3) being higher in Basal-like vs. Luminal breast cancer. Extending these findings to TMAs with more patients (n = 75), we confirmed subtype-specific immune profiles, including enrichment of Treg markers in Basal-likes. This work demonstrated that immune responses can be detected in epithelium-rich tissue, and that TMAs are a viable approach for obtaining important immunoprofiling data. In addition, we found that immune marker expression is associated with breast cancer subtype, suggesting possible prognostic, or targetable differences.

MRI-guided core needle biopsy of the breast: Radiology-pathology correlation and impact on clinical management.

OBJECTIVE: Breast MRI is used to screen high-risk patients and determine extent of disease in breast cancer (BC) patients. The goal of this study was to determine the pathologic correlates of breast MRI abnormalities biopsied under MRI guidance. METHODS: We retrospectively identified 101 MRI-guided core needle biopsies (CNB) of the breast from 79 women over a 4-year period. MRI-detected lesions biopsied with ultrasound or stereotactic guidance were excluded. MRI studies and pathology were reviewed by breast radiologists and pathologists. RESULTS: Of the 79 patients, 72 (91%) had a history of prior (n = 13) or concurrent (n = 59) BC. There were 101 MRI abnormalities: 60 (59%) with non-mass enhancement (NME) and 41 (41%) with mass enhancement. Pathology was benign in 83/101 (82%), including in the majority of NME lesions (43/60, 72%). The most common benign findings were: fibrocystic changes (FCC) (49%), sclerosing lesions (13%), and fibroadenoma (FA) (9%). There were 18 (18%) malignant diagnoses: 8 (44%) invasive lobular carcinoma (ILC), 7 (39%) ductal carcinoma in situ (DCIS), and 3 (17%) invasive ductal carcinoma (IDC). Of the 18 malignant diagnoses, 16 (89%) occurred in 14 unique patients with concurrent BC. Based on the malignant MRI-guided CNB, 6 (46%) of these patients had additional (sentinel lymph node biopsy or contralateral breast surgery) or more extensive (wider lumpectomy) surgery. CONCLUSION: In this series, most MRI-guided CNB of the breast were benign. The vast majority of malignant diagnoses occurred in patients with concurrent BC and frequently resulted in changes in clinical management.

Clinicopathologic features of breast cancer reclassified as HER2-amplified by fluorescence in situ hybridization with alternative chromosome 17 probes.

OBJECTIVE: Dual probe fluorescence in situ hybridization (FISH) assays for determination of human epidermal growth factor receptor 2 (HER2) gene amplification in breast cancer provide a ratio of HER2 to chromosome 17. The ratio may be skewed by copy number alterations (CNA) in the control locus for chromosome 17 (CEP17). We analyzed the impact of alternative chromosome 17 control probes on HER2 status in a series of breast cancers with an emphasis on patients reclassified as amplified. METHODS: Breast cancer patients with equivocal HER2 immunohistochemistry (2+) and equivocal FISH with CEP17 were included. Reclassification of HER2 status was assessed with alternative chromosome 17 control probes (LIS1 and RARA). RESULTS: A total of 40 unique patients with 46 specimens reflexed to alternative chromosome 17 probe testing were identified. The majority (>80%) of patients had pT1-2, hormone receptor-positive tumors with an intermediate or high combined histologic grade. There were 34/46 (73.9%) specimens reclassified as amplified with alternative probes, corresponding to 29/40 (72.5%) patients. Of the patients reclassified as amplified with alternative probes, 34.5% (10/29) received HER2-targeted therapy. CONCLUSION: In this series, the majority of breast cancers tested with alternative chromosome 17 control probes under the 2013 ASCO/CAP Guidelines were converted to HER2-amplified. The treatment data and the clinicopathologic profile of the tumors suggest that most of these patients will neither receive nor benefit from HER2-targeted therapy. The findings support the recommendation in the 2018 ASCO/CAP HER2 Guidelines to discontinue the use of alternative chromosome 17 probes.

Cystic neutrophilic granulomatous mastitis: The Cleveland Clinic experience with diagnosis and management.

Granulomatous mastitis is an uncommon inflammatory disease that typically presents with painful breast lesions. Recent publications have brought to light a specific subset of granulomatous mastitis patients with a distinct histological pattern of disease termed, "cystic neutrophilic granulomatous mastitis" (CNGM). Although many cases of granulomatous lobular mastitis have been thought to be idiopathic, this rare subset of an uncommon disease has been linked to infections with Corynebacterium species. Herein, a cohort of CNGM patients from a large, tertiary care, North-American, academic medical center is presented. Correlative demographic, clinical, radiographic, pathologic, microbiologic, management, and outcomes data are provided. Collaborative communication between specialists to accurately diagnose and manage these patients is essential to decreasing potential morbidity.

Breast cancer risk associated with atypical hyperplasia and lobular carcinoma in situ initially diagnosed on core-needle biopsy.

BACKGROUND: Breast cancer risk estimates for atypical lesions are based primarily on case-control studies of patients with open biopsies. The authors report the cumulative breast cancer incidence after a core biopsy diagnosis of atypical hyperplasia (ductal or lobular) or lobular carcinoma in situ. METHODS: A cohort study with central pathology review was conducted on 393 patients who had core biopsy diagnoses of atypical hyperplasia and lobular carcinoma in situ from 1995 through 2010. Follow-up was available for 255 of 264 patients (97%) at a median of 87 months (range, 3-236 months). RESULTS: There were 212 patients (54%) who were not upgraded on excision and had no personal history of breast cancer. Of these, 21 of 212 (9.9%) developed breast cancer, including 15 invasive carcinomas, 4 ductal carcinomas in situ, 1 pleomorphic lobular carcinoma in situ, and 1 unknown type. The prior core biopsy diagnoses were atypical ductal hyperplasia for 11 patients (52%) and atypical lobular hyperplasia/lobular carcinoma in situ in the remaining 10 patients (48%). The number of atypical foci in the core biopsy was not significantly associated with the subsequent development of breast cancer (P = .42). Of the 15 invasive carcinomas, 11 (73%) were ipsilateral, 11 (73%) were pathologic T1 tumors, 5 (33%) were pathologic N1 tumors, 13 (87%) were estrogen receptor-positive, and 1 (7%) was amplified for human epidermal growth factor receptor 2. CONCLUSIONS: In patients who had an initial diagnosis of atypical hyperplasia or lobular carcinoma in situ on core biopsy, the 7-year cumulative breast cancer incidence was 9.9%. Most tumors were ipsilateral, stage I, estrogen receptor-positive, invasive carcinomas. The current data support close clinical and radiologic follow-up for more than 5 years in this patient population. Cancer 2018;124:459-65. © 2017 American Cancer Society.

Mucocele-like lesions diagnosed on breast core biopsy: Low risk of upgrade and subsequent carcinoma.

Mucocele-like lesions of the breast diagnosed on core biopsy are usually excised to exclude the possibility of partial sampling of an invasive mucinous carcinoma. The goal of this study was to correlate the pathologic and radiologic features of mucocele-like lesions to determine if excision is mandatory. Over a 16 year period we identified 32 patients with mucocele-like lesions diagnosed on 27 (84%) stereotactic and 5 (16%) ultrasound-guided core biopsies. The indications for core biopsy were: calcifications in 24 (75%), a mass in 7 (22%), and a mass with calcifications in 1 (3%). There were 22 (69%) mucocele-like lesions without atypia and 10 (31%) with atypical ductal hyperplasia or detached groups of atypical cells. Of the 22 mucocele-like lesions without atypia, 19 (86%) were excised: 15/19 (79%) were benign, 3/19 (16%) had atypical ductal hyperplasia and 1/19 (5%) had ductal carcinoma in situ. None of the patients with mucocele-like lesions without atypia were upgraded to invasive carcinoma. The single patient who was upgraded to low-grade ductal carcinoma in situ had a history of ductal carcinoma in situ in the same breast. Of the 10 patients with mucocele-like lesions with atypia, 9 (90%) were excised: 5/9 (56%) were benign, 1/9 (11%) had atypical ductal hyperplasia and 3/9 (33%) had invasive carcinoma. Of the patients with mucocele-like lesions with atypia who were upgraded to invasive carcinoma, one had a BIRADS 5 mass and discordant pathology and one had a history of Hodgkin lymphoma and mantle radiation. There were 24 patients with mucocele-like lesions with or without atypia who were not upgraded on excision, and none developed breast cancer after a median of 51 months (range 7-192). These findings indicate that mucocele-like lesions without atypia are unlikely to be upgraded on excision and are associated with a low risk for the subsequent development of carcinoma.

Analytical and clinical performance of progesterone receptor antibodies in breast cancer.

OBJECTIVE: Comparison of analytical and immunohistochemical performance of progesterone receptor (PR) antibodies with correlation to recurrence of invasive breast cancer treated with endocrine therapy. METHODS: The binding-affinity kinetics of PR clones 1E2, 1A6, 16 and 636 were compared using synthetic peptides derived from identified epitopes on a Biacore T200. A cohort of 351 cases (Hormone Receptor (HR)+/HER2-) were stained for PR expression with immunohistochemistry (IHC) and scored according to ASCO/CAP criteria. RESULTS: The stability of the antigen/antibody complex was greater for the 1E2 clone compared to 1A6, 16 and 636 clones. PR IHC on archival tissue resulted in 94.3% (299/317) concordance with clones. CONCLUSION: Clones evaluated in this study had a high level of concordance with IHC despite PR (1E2) demonstrating higher analytical binding properties than other clones. In a minority of cases (1.3% for 1E2 and 2.5% for 636) IHC results could convert estrogen receptor (ER)-/PR- to ER-/PR+ tumors, making these patients potentially eligible for endocrine therapy.

Impact of an alternative chromosome 17 probe and the 2013 American Society of Clinical Oncology and College of American Pathologists guidelines on fluorescence in situ hybridization for the determination of HER2 gene amplification in breast cancer.

BACKGROUND: The dual-probe fluorescence in situ hybridization (FISH) assay for human epidermal growth factor receptor 2 (HER2) gene amplification in breast cancer provides an HER2:CEP17 (centromere enumeration probe for chromosome 17) ratio. Copy number alteration (CNA) in CEP17 may skew this ratio. The authors analyzed the impact of the 2013 American Society of Oncology/College of American Pathologists (ASCO/CAP) guidelines and an alternative chromosome 17 probe on HER2 status in tumor specimens with CEP17 CNA. METHODS: Specimens with CEP17 CNA (n = 310) were selected from 3048 tumor samples that were received from January 2013 to June 2015 for testing with the alternative chromosome 17 probe D17S122. Reclassification of HER2 status was assessed using the 2007 and 2013 ASCO/CAP guidelines. RESULTS: The alternative chromosome 17 probe reclassified 82 of 310 (26.5%) and 87 of 310 (28.1%) tumors using the 2007 and 2013 guidelines, respectively. Of the 41 of 310 tumors (13.2%) that were reclassified from nonamplified to amplified according to 2007 guidelines, 28 of 41 (68.3%) had an average HER2 copy number ≥4.0 and <6.0. The 39 of 310 tumors (12.6%) that were reclassified from equivocal to amplified according to 2013 guidelines had a mean HER2 copy number between ≥4.0 and <6.0. Most of these patients had stage I, hormone receptor-positive, lymph node-negative tumors, which is an unusual clinicopathologic profile for HER2-amplified tumors, and most received HER2-targeted therapy in addition to endocrine therapy. CONCLUSIONS: Reflex testing with an alternative chromosome 17 probe using the 2013 ASCO/CAP guidelines reclassified 28.1% of tumor samples that had CEP17 CNA, converting nearly one-half from equivocal to amplified. The benefit of HER2-targeted therapy in this patient population requires further study. Cancer 2017;123:2230-2239. © 2017 American Cancer Society.

Predictive factors on outcomes in metaplastic breast cancer.

PURPOSE: Metaplastic breast cancer (MBC) is a rare, aggressive variant of breast cancer, with limited data available regarding treatment and outcomes. This study aims to review patients with MBC treated at our tertiary care institution with an emphasis on the role of treatment modality and histologic classification. METHODS: With IRB-approval, we queried our pathology database for patients with MBC diagnosis. All cases were re-evaluated by dedicated breast pathologists and confirmed as MBC breast cancer. Patient demographics, clinical/pathologic histology, and treatment were analyzed with respect to outcomes including local-regional recurrence (LRR), distant metastasis (DM), and overall survival (OS). Univariate and multivariate Cox proportional hazards models were performed to evaluate the impact on outcomes. Kaplan-Meier methods estimated survival. RESULTS: We evaluated 113 patients with MBC diagnosed between 2002 and 2013. Median age was 61 years and median pathologic tumor size 2.5 cm; 76 (67%) were ER/PR/Her2 negative, 83 (74%) grade 3. Median follow-up was 38 months. 47 (42%) underwent breast conservation therapy (BCT), 66 (58%) had mastectomy, 61 (54%) underwent adjuvant radiation (RT), and 85 (75%) had chemotherapy. At 2 and 5 years, the LRR/DM/OS rates were 12%/15%/90% and 21%/35%/69%, respectively. On Cox regression analysis, only adjuvant RT correlated with reduced LRR [RR 3.1 (1.13-9.88), p = 0.027], while chemotherapy, type of surgery, and T-N stage did not. Only T-stage (p = 0.008) correlated with DM, however chemotherapy, RT, surgery type, and N-stage were not. Univariate analysis demonstrated histologic subtype did not significantly correlate with local (p = 0.54) or distant (p = 0.83) disease control. CONCLUSIONS: This study represents among the largest institutional experiences in the outcomes of MBC. At this time, there does not appear to be a clear histologic subset of MBC which has significantly different clinical outcomes from the other subtypes. Although limited in its sample size, this study shows RT remains important in local-regional control.

Lipomatous tumors of the breast: A contemporary review.

Breast tumors with lipomatous or liposarcomatous components are infrequently encountered, but can be a source of diagnostic difficulty if the context of the fatty differentiation is not recognized. Among the true adipocytic tumors, lipoma is the most common lipomatous tumor arising in the breast. Several mammary spindle cell tumors may show adipocytic differentiation, including fibroepithelial tumors and myofibroblastoma. Liposarcomatous components most often arise in malignant phyllodes tumors, as opposed to primary liposarcomas of the breast which are believed to be uncommon. This article will review the spectrum fat-containing tumors of the breast with an emphasis on differential diagnosis and insights from recent molecular studies.

Recommendations for excision following core needle biopsy of the breast: a contemporary evaluation of the literature.

Pathologists frequently encounter non-malignant histological findings in percutaneous core needle biopsies (CNBs). Standards for the management of patients with lesions such as atypical ductal hyperplasia, atypical lobular hyperplasia, and lobular carcinoma in situ, as well as other benign lesions, are not well defined, and recommendations for surgical biopsy or continued clinical and radiological follow-up are inconsistent. The frequency with which these lesions are 'upgraded' to carcinoma in excision specimens is widely variable in the literature. Many CNB studies lack careful radiological-pathological correlation, clear criteria for excision, and clinical follow-up for patients on whom excision was not performed. This review of the recent literature emphasizes studies with radiological-pathological correlation, with the goal of developing a contemporary, evidence-based approach to the management of non-malignant lesions of the breast diagnosed on CNB. The data supporting an emerging consensus on which lesions may not require excision are highlighted. The management of non-malignant lesions diagnosed on magnetic resonance imaging-guided CNB is also discussed.

MET and PTEN gene copy numbers and Ki-67 protein expression associate with pathologic complete response in ERBB2-positive breast carcinoma patients treated with neoadjuvant trastuzumab-based therapy.

BACKGROUND: Pathologic complete response (pCR) after neoadjuvant chemotherapy for breast cancer is associated with improved prognosis in aggressive tumor subtypes, including ERBB2- positive tumors. Recent adoption of pCR as a surrogate endpoint for clinical trials in early stage breast cancer in the neoadjuvant setting highlights the need for biomarkers that, alone or in combination, help predict the likelihood of response to treatment. METHODS: Biopsy specimens from 29 patients with invasive ductal carcinoma treated with trastuzumab-based therapy prior to definitive resection and pathologic staging were evaluated by dual color bright field in situ hybridization (dual ISH) using probes for MET, TOP2A, PTEN, and PIK3CA genes, each paired with centromeric probes to their respective chromosomes (chromosomes 7, 17, 10, and 3). Ki-67 expression was assessed by immunohistochemistry (IHC). Various parameters describing copy number alterations were evaluated for each gene and centromere probe to identify the optimal parameters for clinical relevance. Combinations of ISH parameters and IHC expression for Ki-67 were also evaluated. RESULTS: Of the four genes and their respective chromosomes evaluated by ISH, two gene copy number parameters provided statistically significant associations with pCR: MET gain or loss relative to chromosome 7 (AUC = 0.791, sensitivity = 92 % and specificity = 67 % at optimal cutoff, p = 0.0032) and gain of PTEN (AUC = 0.674, sensitivity = 38 % and specificity = 100 % at optimal cutoff, p = 0.039). Ki-67 expression was also found to associate significantly with pCR (AUC = 0.726, sensitivity = 100 % and specificity = 42 % at optimal cutoff, p = 0.0098). Combining gain or loss of MET relative to chromosome 7 with Ki-67 expression further improved the association with pCR (AUC = 0.847, sensitivity = 92 % and specificity = 83 % at optimal cutoffs, p = 0.0006). CONCLUSIONS: An immunogenotypic signature of low complexity comprising MET relative copy number and Ki-67 expression generated by dual ISH and IHC may help predict pCR in ERBB2-positive breast cancer treated with neoadjuvant chemotherapy and trastuzumab. These findings require validation in additional patient cohorts.

Lobular neoplasia diagnosed on breast Core biopsy: frequency of carcinoma on excision and implications for management.

The appropriate follow-up and treatment for patients with a core biopsy diagnosis of lobular neoplasia (atypical lobular hyperplasia or lobular carcinoma in situ) remains controversial. Several studies have attempted to address this issue, with recommendations ranging from close clinical follow-up or surveillance to mandatory surgical excision in all cases. We report the findings at our institution, where virtually every core needle biopsy diagnosis of lobular neoplasia results in follow-up excision. The goal of the study was to identify potential predictors of upgrade to a more significant lesion. We identified 76 patients over a 15-year period with a core biopsy diagnosis of pure lobular neoplasia and no other high-risk lesions. Subsequent surgical excision identified 10 cases (13%) that were upgraded to carcinoma. Upgrade diagnoses included invasive ductal carcinoma (n=1), invasive lobular carcinoma (n=4), ductal carcinoma in situ (n=3), and pleomorphic lobular carcinoma in situ (n=2). All 10 upgraded cases had imaging findings suspicious for malignancy including irregular masses, asymmetric densities, or pleomorphic calcifications. Of the 10 upgraded cases, 7 were diagnosed as lobular carcinoma in situ on core biopsy. The data support a role for radiologic-pathologic correlation in the evaluation of suspicious breast lesions and suggest that the extent of lobular neoplasia in core biopsy specimens may be an indicator of the likelihood of upgrade to carcinoma.

Management of flat epithelial atypia on breast core biopsy may be individualized based on correlation with imaging studies.

Flat epithelial atypia of the breast commonly co-exists with atypical ductal hyperplasia, lobular neoplasia, and indolent forms of invasive carcinomas such as tubular carcinoma. Most patients with pure flat epithelial atypia on core biopsy undergo surgical excision to evaluate for carcinoma in the adjacent breast tissue. Studies to date have reported varying upgrade rates with most recommending follow-up excision. These studies have often lacked detailed radiographic correlation, central review by breast pathologists and information regarding the biology of the carcinomas identified upon excision. In this study, we report the frequency of upgrade to invasive carcinoma or ductal carcinoma in situ in excision specimens following a diagnosis of pure flat epithelial atypia on core biopsy. Radiographic correlation is performed for each case and grade/receptor status of detected carcinomas is reported. Seventy-three (73) core biopsies containing pure flat epithelial atypia were identified from our files, meeting inclusion criteria for the study. In the subsequent excision biopsies, five (7%) cases contained invasive carcinoma or ductal carcinoma in situ and seventeen (23%) contained atypical ductal hyperplasia or lobular neoplasia. All of the ductal carcinoma in situ cases with estrogen receptor results were estrogen receptor positive and intermediate grade. The invasive tumors were small (pT1a) hormone receptor-positive, HER2-negative, low-grade invasive ductal or tubular carcinomas with negative sentinel lymph-node biopsies. No upgrades were identified in the 14 patients who had all of their calcifications removed by the stereotactic core biopsy. Our rate of upgrade to carcinoma, once cases with discordant imaging are excluded, is at the lower end of the range reported in the literature. Given the low upgrade rate and indolent nature of the carcinomas associated with flat epithelial atypia, case management may be individualized based on clinical and radiographic findings. Excision may not be necessary for patients without remaining calcifications following core biopsy.