NCCN Guidelines® Insights: Breast Cancer Screening and Diagnosis, Version 1.2023.

The NCCN Guidelines for Breast Cancer Screening and Diagnosis provide health care providers with a practical, consistent framework for screening and evaluating a spectrum of clinical presentations and breast lesions. The NCCN Breast Cancer Screening and Diagnosis Panel is composed of a multidisciplinary team of experts in the field, including representation from medical oncology, gynecologic oncology, surgical oncology, internal medicine, family practice, preventive medicine, pathology, diagnostic and interventional radiology, as well as patient advocacy. The NCCN Breast Cancer Screening and Diagnosis Panel meets at least annually to review emerging data and comments from reviewers within their institutions to guide updates to existing recommendations. These NCCN Guidelines Insights summarize the panel's decision-making and discussion surrounding the most recent updates to the guideline's screening recommendations.

Aromatase inhibitors and contralateral breast cancer in BRCA mutation carriers.

BACKGROUND: Deleterious BRCA mutations confer a significant lifetime risk of breast cancer (BC) as well as contralateral BC (CBC) in patients who do not undergo prophylactic mastectomy. Prior reports have suggested that tamoxifen reduces the risk of CBC in BRCA mutation carriers. Whether aromatase inhibitors (AI) have the same effect is unknown. METHODS: This is a retrospective review of patients diagnosed with non-metastatic ER+ BC between 2004 and 2014 with known BRCA mutation status. Patients were followed from primary diagnosis until CBC diagnosis or death. Median follow-up was 11.5 years. Risk of CBC was evaluated as time to event. RESULTS: 935 subjects were included in this analysis, with 53 BRCA1 mutation carriers, and 94 BRCA2 mutation carriers. Median age at diagnosis was 42.7 years. Seventy-two percent (676) received tamoxifen and 43% (405) received AI. A total of 66 CBCs occurred, of which 10% (15/147) occurred in BRCA mutation carriers vs 6.5% (51/788) in BRCA wild type. Multivariate analyses indicated that BRCA status and AI use were significantly associated with CBC risk. AI use resulted in a significant reduction in risk of CBC (HR 0.44, p = 0.004) regardless of the BRCA mutation status. Tamoxifen use was not associated with reduced risk of CBC. CONCLUSIONS: This is the first report showing that AIs reduce the risk of CBC in BRCA mutation carriers. The potential role of AIs as chemoprevention should be validated in larger independent cohorts.

Perceptions of Conflicting Breast Cancer Screening Recommendations Among Racially/Ethnically Diverse Women: a Multimethod Study.

BACKGROUND: Conflicting breast cancer screening recommendations have the potential to diminish informed decision making about screening. OBJECTIVE: We examined the knowledge, attitudes, and intentions related to divergent recommendations for breast cancer screening among racially/ethnically diverse women. DESIGN: We used a multimethod study design employing focus groups and questionnaires. Focus groups included: (1) two 10-min presentations on the national screening recommendations and the potential benefits and harms of screening and (2) an interactive discussion. Data were collected: 8/3/2017 to 11/19/2019. Analysis occurred from 1/21/2019 to 7/24/2020. PARTICIPANTS: Participants were (1) women 40-75 years; (2) English or Spanish speaking; (3)self-identified as Latina, Black, or non-Latina White; and (4) no known increased risk for breast cancer. MAIN MEASURES: Main outcomes were participants' knowledge and perceptions of benefits and harms of screening mammography and their screening intentions. Focus groups were transcribed and analyzed using a qualitative descriptive approach. Quantitative data were summarized using descriptive statistics. KEY RESULTS: One hundred thirty-four women (n=52, 40-49 years; n=82, 50-75 years) participated in 28 focus groups. Participants were Latina (n=44); Black (n=51); and non-Latina White (n=39). Approximately one-quarter (n=32) had limited health literacy and almost one-fifth (n=23) had limited numeracy. In the context of differing national screening recommendations, participants questioned the motives of the recommendation-making agencies, including the role of costs and how costs were considered when making screening recommendations. Participants expressed concern that they were not represented (e.g., race/ethnicity) in the data informing the recommendations. Immediately following the focus groups, most participants expressed intention to screen within the upcoming year (pre n=100 vs. post n=107). CONCLUSIONS: Divergent breast cancer screening recommendations may lead to mistrust and paradoxically reinforce high overall enthusiasm for screening.

Salutary effects of moderate but not high intensity aerobic exercise training on the frequency of peripheral T-cells associated with immunosenescence in older women at high risk of breast cancer: a randomized controlled trial.

BACKGROUND: Immunosenescence is described as age-associated changes within the immune system that are responsible for decreased immunity and increased cancer risk. Physically active individuals have fewer 'senescent' and more naïve T-cells compared to their sedentary counterparts, but it is not known if exercise training can rejuvenate 'older looking' T-cell profiles. We determined the effects of 12-weeks supervised exercise training on the frequency of T-cell subtypes in peripheral blood and their relationships with circulating levels of the muscle-derived cytokines (i.e. 'myokines') IL-6, IL-7, IL-15 and osteonectin in older women at high risk of breast cancer. The intervention involved 3 sessions/week of either high intensity interval exercise (HIIT) or moderate intensity continuous exercise (MICT) and were compared to an untrained control (UC) group. RESULTS: HIIT decreased total granulocytes, CD4+ T-cells, CD4+ naïve T-cells, CD4+ recent thymic emigrants (RTE) and the CD4:CD8 ratio after training, whereas MICT increased total lymphocytes and CD8 effector memory (EM) T-cells. The change in total T-cells, CD4+ naïve T-cells, CD4+ central memory (CM) T-cells and CD4+ RTE was elevated after MICT compared to HIIT. Changes in [Formula: see text] after training, regardless of exercise prescription, was inversely related to the change in highly differentiated CD8+ EMRA T-cells and positively related to changes in ß2-adrenergic receptor (ß2-AR) expression on CM CD4+ and CM CD8+ T-cells. Plasma myokine levels did not change significantly among the groups after training, but individual changes in IL-7 were positively related to changes in the number of ß2-AR expressing CD4 naïve T cells in both exercise groups but not controls. Further, CD4 T-cells and CD4 naive T-cells were negatively related to changes in IL-6 and osteonectin after HIIT but not MICT, whereas CD8 EMRA T-cells were inversely related to changes in IL-15 after MICT but not HIIT. CONCLUSIONS: Aerobic exercise training alters the frequency of peripheral T-cells associated with immunosenescence in middle aged/older women at high risk of breast cancer, with HIIT (pro-senescent) and MICT (anti-senescent) evoking divergent effects. Identifying the underlying mechanisms and establishing whether exercise-induced changes in peripheral T-cell numbers can alter the risk of developing breast cancer warrants investigation.

The impact of high-intensity interval exercise training on NK-cell function and circulating myokines for breast cancer prevention among women at high risk for breast cancer.

PURPOSE: Preclinical evidence suggests that natural killer cell (NK-cell) function and myokines facilitate the protective effects of exercise for breast cancer prevention. Since higher-intensity exercise acutely promotes greater mobilization and larger changes in NK-cell cytotoxicity than lower-intensity, high-intensity interval training (HIIT) might offer increased immune protection compared to moderate-intensity continuous-training (MICT). This study compared a 12-week HIIT program to a 12-week MICT program and usual care on changes in resting NK-cell function and circulating myokines among women at high risk for breast cancer. METHODS: Thirty-three women were randomized to HIIT, MICT, or usual care, for a supervised exercise intervention. Blood was collected at baseline and end-of-study. The cytotoxic activity of CD3-/CD56+ NK-cells against the K562 target cell line in vitro was determined by flow cytometry. Circulating myokines (IL-15, IL-6, irisin, OSM, osteonectin, IL-7) were assessed with luminex multiplex assays and ELISA. One-way ANOVA and paired sample t-tests assessed between- and within-group differences, respectively. Pearson correlation coefficients determined relationships between baseline fitness and change variables. RESULTS: Significant differences were not observed between groups for change in NK-cell function or circulating myokines (p > 0.05). Significant correlations were only observed for baseline peak aerobic capacity (ml/kg/min) and change in NK-cell-specific lysis (r = - 0.43, p = 0.02) and hemacytotoxicity for the total sample (r = - 0.46, p = 0.01). CONCLUSION: Our findings suggest that exercise intensity may not significantly impact change in resting NK-cell function and circulating myokines among women at high risk for breast cancer. Structured exercise training may have a larger impact on NK-cell function in those with lower levels of cardiorespiratory fitness. CLINICAL TRIAL REGISTRATION: NCT02923401; Registered on October 4, 2016.

The role of magnetic resonance imaging in patients with palpable breast abnormalities and negative mammographic and sonographic findings.

OBJECTIVE OR PURPOSE OF STUDY: The objective of this retrospective study was to determine the frequency of positive findings on breast magnetic resonance imaging (MRI) in patients with palpable breast abnormalities in the setting of negative mammographic and sonographic evaluations. MATERIALS, METHODS, AND PROCEDURES: Consecutive patients undergoing breast MRI for palpable abnormalities from January 1, 2005 to December 31, 2015 were identified for this retrospective study. Those with preceding imaging (mammograms or ultrasounds) demonstrating positive findings related to the palpable abnormalities were excluded. The location and the duration of the symptoms, the type and the location of the abnormal MRI findings, and their relationships to the symptoms were recorded. Clinical and imaging follow-up as well as the type and the resultant biopsies were recorded. Patients with less than two years of imaging or clinical follow-up were excluded from the study. RESULTS: 22 004 women presented with palpable abnormalities at one breast imaging center between January 1, 2005 and December 31, 2015. Nine thousand and three hundred and thirty-four patients had negative or benign findings on mammography, ultrasound, or mammography plus ultrasound. Thirty-one patients underwent MRI with the complaint of palpable abnormalities despite negative or benign mammographic and/or sonographic findings. Their age range was between 32 and 74 years, and their mean age was 49 years. Of those who had MRI, twenty-one patients had negative MRI findings. Six patients had negative concordant results for the palpable abnormalities and benign incidental findings. Three patients had benign concordant results for the palpable abnormalities, and one patient had incidental atypia. Twenty-eight patients had negative MRI results in the area of the palpable abnormality, and none of these patients underwent biopsy. Of the 31 cases, four patients (13%) underwent additional examinations (three second-look ultrasounds and one bone scan) after MRI. Five patients (16%) underwent MRI-guided biopsies, two patients (6%) underwent ultrasound-guided biopsies, and one patient (3%) had an excision. All biopsies showed benign results. The Gail risk score was calculated for 22 of them and the mean 5-year risk was 1.64 and the mean lifetime risk was 12.51. CONCLUSION: Breast MRI to evaluate palpable abnormalities after negative mammography and ultrasound results in a low yield for malignancy. The majority of patients (67.7%) had negative MRI examinations, and there were no malignancies detected. Our findings lead us to believe that there are no data to encourage the use of MRI in patients with palpable abnormalities and negative mammographic and/or ultrasound studies.

Preferences for Communicating about Breast Cancer Screening Among Racially/Ethnically Diverse Older Women.

Differences exist across breast cancer screening guidelines regarding frequency of screening and age of discontinuation for older women (≥70 years) at average risk for breast cancer. These differences highlight concerns about the benefits and harms of screening, and may negatively impact older women's ability to make informed screening decisions. This study examined preferences for communicating about screening mammography among racially/ethnically diverse, older women. In-depth interviews were conducted with 59 women with no breast cancer history. Non-proportional quota sampling ensured roughly equal numbers on age (70-74 years, ≥75 years), race/ethnicity (non-Hispanic/Latina White, non-Hispanic/Latina Black, Hispanic/Latina), and education (≤high school diploma, >high school diploma). Interviews were audio-recorded, transcribed, and analyzed using NVivo 10. Thematic analyses revealed that rather than being told to get mammograms, participants wanted to hear about the benefits and harms of screening mammography, including overdiagnosis. Participants recommended that this information be communicated via physicians or other healthcare providers, included in brochures/pamphlets, and presented outside of clinical settings (e.g., in senior groups). Results were consistent regardless of participants' age, race/ethnicity, or education. Findings revealed that older women desire information about the benefits and harms of screening mammography, and would prefer to learn this information through discussions with healthcare providers and multiple other formats.

Screening Mammography for Average-Risk Women: The Controversy and NCCN's Position.

Breast cancer remains the most common nonskin cancer among women and a leading cause of morbidity and mortality. Early detection through screening and advances in treatment have contributed to a 39% mortality reduction in the United States since 1990. The NCCN Guidelines for Breast Cancer Screening and Diagnosis recommend annual mammographic screening for average-risk women beginning at age 40 years. Mammographic screening and subsequent treatment reduces breast cancer mortality based on a wide range of studies. This article highlights NCCN's position on screening mammography and the screening controversy.

Breast Cancer Screening and Diagnosis, Version 3.2018, NCCN Clinical Practice Guidelines in Oncology.

The NCCN Guidelines for Breast Cancer Screening and Diagnosis have been developed to facilitate clinical decision making. This manuscript discusses the diagnostic evaluation of individuals with suspected breast cancer due to either abnormal imaging and/or physical findings. For breast cancer screening recommendations, please see the full guidelines on NCCN.org.

Resistance to discontinuing breast cancer screening in older women: A qualitative study.

OBJECTIVE: Screening mammography is associated with reduced breast cancer-specific mortality; however, among older women, evidence suggests that the potential harms of screening may outweigh the benefits. We used a qualitative approach to examine the willingness of older women from different racial/ethnic groups to discontinue breast cancer screening. METHODS: Women ≥70 years of age who reported having a screening mammogram in the past 3 years and/or reported that they intended to continue screening in the future were recruited for in-depth interviews. Participants who intended to continue screening were asked to describe how the following hypothetical scenarios would impact a decision to discontinue screening: health concerns or limited life expectancy, a physician's recommendation to discontinue, reluctance to undergo treatment, and recommendations from experts or governmental panels to stop screening. Semi-structured, face-to-face interviews were audio-recorded. Data coding and analysis followed inductive and deductive approaches. RESULTS: Regardless of the scenario, participants (n = 29) expressed a strong intention to continue screening. Based on the hypothetical physician recommendations, intentions to continue screening appeared to remain strong. They did not envision a change in their health status that would lead them to discontinue screening and were skeptical of expert/government recommendations. There were no differences observed according to age, race/ethnicity, or education. CONCLUSIONS: Among older women who planned to continue screening, intentions to continue breast cancer screening appear to be highly resilient and resistant to recommendations from physicians or expert/government panels.

User Perceptions and Reactions to an Online Cancer Risk Assessment Tool: a Process Evaluation of Cancer Risk Check.

Online cancer risk assessment tools, which provide personalized cancer information and recommendations based on personal data input by users, are a promising cancer education approach; however, few tools have been evaluated. A randomized controlled study was conducted to compare user impressions of one tool, Cancer Risk Check (CRC), to non-personalized educational information delivered online as series of self-advancing slides (the control). CRC users (N = 1452) rated the tool to be as interesting as the control (p > .05), but users were more likely to report that the information was difficult to understand and not applicable to them (p < .05). Information seeking and sharing also were lower among CRC users; thus, although impressions of CRC were favorable, it was not shown to be superior to existing approaches. We hypothesized CRC was less effective because it contained few visual and graphical elements; therefore, CRC was compared to a text-based control (online PDF file) post hoc. CRC users rated the information to be more interesting, less difficult to understand, and better able to hold their attention (p < .05). Post hoc results suggest the visual presentation of risk is critical to tool success.

Epidemiological risk factors associated with inflammatory breast cancer subtypes.

BACKGROUND: In this single-institution case-control study, we identified risk factors associated with inflammatory breast cancer (IBC) subtypes based on staining of estrogen receptor (ER), progesterone receptor (PR) and expression of human epidermal growth factor 2 (HER2neu) to determine distinct etiologic pathways. METHODS: We identified 224 women with IBC and 396 cancer-free women seen at the MD Anderson Cancer Center. Multinomial logistic regression was used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) for associations between breast cancer risk factors and the IBC tumor subtypes: luminal (ER+ and/or PR+/HER2neu-), HER2neu+ (any ER and PR, HER2neu+), and triple-negative (ER-/PR-/HER2neu-). RESULTS: In multivariable analysis, compared with women age ≥26 at first pregnancy, women age <26 had a higher risk of triple-negative IBC (OR 3.32, 95% CI 1.37-8.05). Women with a history of breast-feeding had a lower risk of triple-negative (OR 0.30; 95% CI 0.15-0.62) and luminal IBC (OR 0.35, 95% CI 0.18-0.68). A history of smoking was associated with an increased risk of luminal IBC (OR 2.37; 95% CI 1.24-4.52). Compared with normal-weight women, those who were overweight or obese (body mass index ≥25 kg/m(2)) had a higher risk of all three tumor subtypes (p < 0.01 for all subtypes). CONCLUSION: Overweight or obese status is important modifiable risk factor for IBC of any subtype. Modifiable risk factors, age at first pregnancy (≥26), breast-feeding, and smoking may be associated with specific IBC subtypes. These results highlight the importance of evaluating epidemiologic risk factors for IBC for the identification of subtype-specific prevention strategies.

Chemoprevention for Breast Cancer.

BACKGROUND: Many women at increased risk for breast cancer could benefit from preventive therapy. Preventive therapy options for breast cancer risk reduction have expanded in the last few years to include both selective receptor modulators (tamoxifen and raloxifene) and aromatase inhibitors (anastrozole and exemestane). METHODS: Risk factors that place women at high risk for breast cancer, as well as risk calculation models appropriate for the selection of candidates for preventive therapy, are presented, followed by a review of current guidelines for chemoprevention and results of chemoprevention trials. RESULTS: The modified Gail model or Breast Cancer Risk Assessment Tool is the most widely utilized risk assessment calculator to determine eligibility for chemoprevention. Women most likely to benefit from preventive therapy include those at high risk under the age of 50 years and those with atypical hyperplasia. Physician and patient barriers limit widespread acceptance and adherence to preventive therapy. CONCLUSIONS: Published guidelines on chemoprevention for breast cancer have been updated to increase awareness and encourage discussion between patients and their physicians regarding evidence-based studies evaluating the benefits of preventive options for women at increased risk for breast cancer. However, even with increasing awareness and established benefits of preventive therapy, the uptake of chemoprevention has been low, with both physician and patient barriers identified. It is prudent that these barriers be overcome to enable high-risk women with a favorable risk-to-benefit ratio to be offered chemoprevention to reduce their likelihood of developing hormone receptor-positive breast cancer.

Breast Cancer Risk Reduction, Version 2.2015.

Breast cancer is the most frequently diagnosed malignancy in women in the United States and is second only to lung cancer as a cause of cancer death. To assist women who are at increased risk of developing breast cancer and their physicians in the application of individualized strategies to reduce breast cancer risk, NCCN has developed these guidelines for breast cancer risk reduction.

Feasibility of a patient decision aid about lung cancer screening with low-dose computed tomography.

OBJECTIVE: New clinical guidelines endorse the use of low-dose computed tomography (LDCT) for lung cancer screening among selected heavy smokers while recommending patients be counseled about the potential benefits and harms. We developed and field tested a brief, video-based patient decision aid about lung cancer screening. METHODS: Smokers in a cancer center tobacco treatment program aged 45 to 75 years viewed the video online between November 2011 and September 2012. Acceptability, knowledge, and clarity of values related to the decision were assessed. RESULTS: Fifty-two patients completed the study (mean age=58.5 years; mean duration smoking=34.8 years). Acceptability of the aid was high. Most patients (78.8%) indicated greater interest in screening after viewing the aid. Knowledge about lung cancer screening increased significantly as a result of viewing the aid (25.5% of questions answered correctly before the aid, and 74.8% after; P<.01) although understanding of screening eligibility remained poor. Patients reported being clear about which benefits and harms of screening mattered most to them (94.1% and 86.5%, respectively). CONCLUSIONS: Patients have high information needs related to lung cancer screening. A video-based decision aid may be helpful in promoting informed decision-making, but its impact on lung cancer screening decisions needs to be explored.

Efficacy of Cobas HPV testing for predicting grade 2+ cervical intraepithelial neoplasia in a cancer prevention center and a gynecologic oncology clinic: A single-institution experience.

BACKGROUND: To evaluate the efficacy of Cobas human papillomavirus (HPV) testing to predict cervical intraepithelial neoplasia of grade 2 or higher (CIN2+), Cobas HPV testing results were correlated with follow-up biopsy in patients from Cancer Prevention Center (CPC) and Gynecologic Oncology Clinic (GOC) of The University of Texas MD Anderson Cancer Center. METHODS: Institutional data for patients who underwent Cobas HPV and Papanicolaou (Pap) cytology cotesting from 2019 to 2020 were retrospectively reviewed. Surgical follow-up results were compared with Cobas HPV testing results in two populations. RESULTS: A total of 2226 patients, including 921 women (mean age, 55.2 years) seen at the CPC and 1305 women (mean age, 49.3 years) seen at the GOC, were included. Specimens from GOC patients had a significantly higher HPV positivity rate than did those from CPC patients (22.9% vs. 10.1%; p < .001). Cobas HPV testing was positive in all seven CPC patients with surgical follow-up results showing CIN2+. Among 36 GOC patients with CIN2+ lesions, five patients had HPV-/Pap+ testing results. Although only seven CPC patients had CIN2+, Cobas HPV testing showed 100% sensitivity for predicting CIN2+ in this group. Sensitivity for CIN2+ was 86.5% in the GOC group, whereas 13.9% of GOC patients with CIN2+ had negative HPV testing results. CONCLUSIONS: Cobas HPV testing was highly efficacious for predicting CIN2+ lesions in the low-risk CPC population, which supports HPV primary screening for cervical cancer in low-risk populations. For high-risk patients, especially those with a history of CIN2+/cervical cancer, HPV/Pap cotesting may still be necessary to maintain a high clinical sensitivity for CIN2+.

Effects of vitamin D supplementation on a deep learning-based mammographic evaluation in SWOG S0812.

Deep learning-based mammographic evaluations could noninvasively assess response to breast cancer chemoprevention. We evaluated change in a convolutional neural network-based breast cancer risk model applied to mammograms among women enrolled in SWOG S0812, which randomly assigned 208 premenopausal high-risk women to receive oral vitamin D3 20 000 IU weekly or placebo for 12 months. We applied the convolutional neural network model to mammograms collected at baseline (n = 109), 12 months (n = 97), and 24 months (n = 67) and compared changes in convolutional neural network-based risk score between treatment groups. Change in convolutional neural network-based risk score was not statistically significantly different between vitamin D and placebo groups at 12 months (0.005 vs 0.002, P = .875) or at 24 months (0.020 vs 0.001, P = .563). The findings are consistent with the primary analysis of S0812, which did not demonstrate statistically significant changes in mammographic density with vitamin D supplementation compared with placebo. There is an ongoing need to evaluate biomarkers of response to novel breast cancer chemopreventive agents.

Nipple Discharge Imaging Evaluation with Mammography, Ultrasound, Galactography, and MRI.

RATIONALE AND OBJECTIVE: To determine the diagnostic yield of various imaging tests used to evaluate nipple discharge. MATERIALS AND METHODS: A single institution, IRB-approved, retrospective study was performed of 320 consecutive patients presenting with nipple discharge. Imaging and pathology were reviewed to determine the yield for malignancy, atypical high-risk lesions (HRLs), and intraductal papillomas (IDPs). RESULTS: Of the 320 patients, pathology or follow up confirmed 40 breast malignancies (40/320, 12.5%),14 atypical HRLs (14/320, 4.4%), 71 IDPs (71/320, 22.2%), 48 other benign pathologies (48/320,15.0%), and 147 unknown but benign cases (147/320, 45.9%). Physiologic discharge characteristics were observed in a minority of malignant cases: nonspontaneous (4/40, 10.0%); neither bloody nor clear (4/40, 10.0%); bilateral (3/40, 7.5%). Malignancy was associated with older age (p < 0.001) and bloody discharge (odds ratio 6.5, p < 0.0001). The combination of digital mammography and ultrasound had a 93% sensitivity and a 98% NPV, while contrast enhanced MRI (CE-MRI) had a 100% sensitivity and a 100% NPV for malignancy. Only three galactography examinations were performed among the malignant cohort, with minimal contribution (1 of 3) to the diagnostic evaluation. In this case, galactography findings helped determine imaging-pathology discordance, prompting a recommendation for surgical excision and subsequently a malignant diagnosis. CONCLUSION: The combination of mammography and ultrasonography detected 93% of breast malignancies associated with nipple discharge and had a 98% NPV for malignancy. The value of CE-MRI is its ability to detect the remaining malignancies, not detected on mammography or ultrasound, and its ability to obviate the need for surgical duct excision.

Isolated Flat Epithelial Atypia: Upgrade Outcomes After Multidisciplinary Review-Based Management Using Excision or Imaging Surveillance.

Objective: To compare flat epithelial atypia (FEA) upgrade rates after excision versus surveillance and to identify variables associated with upgrade. Methods: This single-institution retrospective study identified isolated FEA cases determined by percutaneous biopsy from April 2005 through July 2022 with excision or ≥2 years surveillance. All cases were recommended for excision or surveillance based on multidisciplinary discussion of clinical, imaging, and pathologic variables with emphasis on sampling adequacy and significant atypia. Truth was determined by pathology at excision or the absence of cancer on surveillance. Upgrade was defined as cancer occurring ≤2 cm from the biopsy site. Demographic, imaging, and biopsy variables were compared between those that did and did not upgrade. Results: Among 112 cases of isolated FEA, imaging findings included calcifications in 81.3% (91/112), MRI lesions in 11.6% (13/112), and distortions or masses in 7.1% (8/112). Excision was recommended in 12.5% (14/112) and surveillance in 87.5% (98/112) of cases. Among those recommended for excision, 28.6% (4/14) of cases were upgraded, all to ductal carcinoma in situ. In those recommended for surveillance, 1.0% (1/98) were upgraded to invasive cancer. Overall, FEA had a 4.5% (5/112) upgrade rate, and 2.7% (3/112) also developed cancer >2 cm from the FEA. There were no significant differences in demographic, imaging, and biopsy variables between those that did and did not upgrade to cancer. Conclusion: Multidisciplinary management of isolated FEA distinguishes those at higher risk of upgrade to cancer (28.6%) in whom surgery is warranted from those at low risk of upgrade (1.0%) who can be managed non-operatively.