Locoregional Therapies for Primary and Metastatic Breast Cancer: AJR Expert Panel Narrative Review.

Minimally invasive locoregional therapies have a growing role in the multidisciplinary treatment of primary and metastatic breast cancer. Factors contributing to the expanding role of ablation for primary breast cancer include earlier diagnosis, when tumors are small, and increased longevity of patients whose condition precludes surgery. Cryoablation has emerged as the leading ablative modality for primary breast cancer owing to its wide availability, the lack of need for sedation, and the ability to monitor the ablation zone. Emerging evidence suggests that in patients with oligometastatic breast cancer, use of locoregional therapies to eradicate all disease sites may confer a survival advantage. Evidence also suggests that transarterial therapies-including chemoembolization, chemoperfusion, and radioembolization-may be helpful to some patients with advanced liver metastases from breast cancer, such as those with hepatic oligoprogression or those who cannot tolerate systemic therapy. However, the optimal modalities for treatment of oligometastatic and advanced metastatic disease remain unknown. Finally, locoregional therapies may produce tumor antigens that in combination with immunotherapy drive anti-tumor immunity. Although key trials are ongoing, additional prospective studies are needed to establish the inclusion of interventional oncology in societal breast cancer guidelines to support further clinical adoption and improved patient outcomes.

Survival Outcomes in Women with Unilateral, Triple-Negative, Breast Cancer Correlated with Contralateral Prophylactic Mastectomy.

BACKGROUND: Despite increased utilization of contralateral prophylactic mastectomy (CPM), there is insufficient evidence that it improves survival in average-risk women with unilateral breast cancer. CPM may be of heightened interest to patients with triple negative breast cancer (TNBC) because these patients are more likely to have BRCA1 mutation-associated disease and are not candidates for the chemoprevention benefits of adjuvant endocrine therapy. METHODS: Survival and recurrence outcomes were evaluated for all TNBC patients from a multi-institutional database (1999-2018) at two academic cancer programs in two metropolitan cities of the Northeast and Midwest. Median follow-up time was 3.7 years. RESULTS: Seven hundred and nighty six TNBC patients were evaluated and 15.45% underwent CPM. Women undergoing CPM were more likely to be white (p < 0.001), younger (p < 0.001), and underwent genetic testing (p < 0.001). A borderline survival benefit was observed for TNBC patients undergoing CPM (5-year overall survival 95.1% vs. 85.0%; p = 0.05). There was no difference in survival when BRCA mutation carriers were excluded (5-year overall survival 94.1% vs. 85.2%; p = 0.12). For BRCA mutation carriers, a numeric trend was observed for improved survival for patients undergoing CPM (5-year overall survival 97.2% vs. 84.1%; p = 0.35). Among patients not undergoing CPM, the rate of developing a new primary breast cancer was 2.2% (15/673). Among these 15 patients, 20% (3/15) were known BRCA mutation carriers. CONCLUSIONS: Our data demonstrate no survival benefit for TNBC patients without BRCA1/2 mutations undergoing CPM.

Benefit of adjuvant chemotherapy in node-negative T1a versus T1b and T1c triple-negative breast cancer.

PURPOSE: National comprehensive cancer network guidelines recommend delivery of adjuvant chemotherapy in node-negative triple-negative breast cancer (TNBC) if the tumor is > 1 cm and consideration of adjuvant chemotherapy for T1b but not T1a disease. These recommendations are based upon sparse data on the role of adjuvant chemotherapy in T1a and T1b node-negative TNBC. Our objective was to clarify the benefits of chemotherapy for patients with T1N0 TNBC, stratified by tumor size. METHODS: We performed a retrospective analysis of survival outcomes of TNBC patients at two academic institutions in the United States from 1999 to 2018. Primary tumor size, histology, and nodal status were based upon surgical pathology. The Kaplan-Meier plot and 5-year unadjusted survival probability were evaluated. RESULTS: Among 282 T1N0 TNBC cases, the status of adjuvant chemotherapy was known for 258. Mean follow-up was 5.3 years. Adjuvant chemotherapy was delivered to 30.5% of T1a, 64.7% T1b, and 83.9% T1c (p < 0.0001). On multivariable analysis, factors associated with delivery of adjuvant chemotherapy were tumor size and grade 3 disease. Improved overall survival was associated with use of chemotherapy in patients with T1c disease (93.2% vs. 75.2% p = 0.008) but not T1a (100% vs. 100% p = 0.3778) or T1b (100% vs. 95.8% p = 0.2362) disease. CONCLUSION: Our data support current guidelines indicating benefit from adjuvant chemotherapy in node-negative TNBC associated with T1c tumors but excellent outcomes were observed in the cases of T1a and T1b disease, regardless of whether adjuvant chemotherapy was delivered.

Radial Scars and Complex Sclerosing Lesions of the Breast: Prevalence of Malignancy and Natural History Under Active Surveillance.

BACKGROUND: When needle core biopsies (NCBs) of the breast reveal radial scar or complex sclerosing lesions (RSLs), excision is often recommended despite a low risk of malignancy in the modern era. The optimal management of NCBs revealing RSLs is controversial, and understanding of the natural history of unresected RSLs is limited. METHODS: We retrospectively analyzed pathology and imaging data from 148 patients with NCB revealing RSL without atypia from 2015 to 2019 to determine the prevalence of malignancy and the behavior of RSLs undergoing active surveillance (AS). RESULTS: The mean age of patients was 52 years, and most lesions were screen-detected (91%). The median lesion size was 6.0 mm (range 2-39). Most patients (66%, n = 98) underwent immediate surgery, while 34% (n = 50) of patients underwent AS, with a median follow-up of 16 months (range 6-51). Of the excised RSLs, 99% (n = 97) were benign and 1% (n = 1) revealed ductal carcinoma in situ (DCIS). In 17% (n = 17) of cases, additional high-risk lesions were discovered upon excision. Among the 50 patients undergoing AS, no lesions progressed on interval imaging. CONCLUSIONS: In this cohort, 99% of RSLs undergoing excision were benign, 1% revealed DCIS, and there were no invasive cancers. In the first study of patients with RSLs undergoing AS, we found that all lesions either remained stable or resolved. We propose that the vast majority of patients with RSL on NCB can be safely offered AS, and that routine excision is a low-value intervention.

Cryoablation Without Excision for Low-Risk Early-Stage Breast Cancer: 3-Year Interim Analysis of Ipsilateral Breast Tumor Recurrence in the ICE3 Trial.

BACKGROUND: The ICE3 trial is designed to evaluate the safety and efficacy of breast cryoablation, enabling women older than 60 years with low-risk early-stage breast cancers to benefit from a nonsurgical treatment and to avoid the associated surgical risks. METHODS: The ICE3 trial is a prospective, multi-center, single-arm, non-randomized trial including women age 60 years or older with unifocal, ultrasound-visible invasive ductal carcinoma size 1.5 cm or smaller and classified as low to intermediate grade, hormone receptor (HR)-positive, and human epidermal growth factor receptor 2 (HER2)-negative. Ipsilateral breast tumor recurrence (IBTR) at 5 years was the primary outcome. A 3-year interim analysis of IBTR was performed, and the IBTR probability was estimated using the Kaplan-Meier method. RESULTS: Full eligibility for the study was met by 194 patients, who received successful cryoablation per protocol. The mean age was 75 years (range, 55-94 years). The mean tumor length was 8.1 mm (range, 8-14.9 mm), and the mean tumor width was 7.4 mm (range, 2.8-14 mm). During a mean follow-up period of 34.83 months, the IBTR rate was 2.06% (4/194 patients). Device-related adverse events were reported as mild in 18.4% and moderate in 2.4% of the patients. No severe device-related adverse events were reported. More than 95% of the patients and 98% of the physicians reported satisfaction with the cosmetic results at the clinical follow-up evaluation. CONCLUSIONS: Breast cryoablation presents a promising alternative to surgery while offering the benefits of a minimally invasive procedure with minimal risks. Further study within a clinical trial or registry is needed to confirm cryoablation as a viable alternative to surgical excision for appropriately selected low-risk patients.

Fibroepithelial Lesions (FELs) of the Breast: Is Routine Excision Always Necessary?

BACKGROUND: When needle core biopsies (NCBs) of the breast reveal fibroepithelial lesions (FELs), excision is often performed to rule out a phyllodes tumor (PT), despite low malignancy rates. Consequently, the natural history of observed FELs is not well described. We analyzed the malignancy risk in excised FELs and the natural history of FELs undergoing active surveillance (AS). METHODS: We retrospectively studied the pathology and imaging records of 215 patients with FELs (n = 252) diagnosed on NCB. Incidence of growth was determined by Kaplan-Meier method. RESULTS: Of 252 FELs, 80% were immediately excised and 20% underwent AS. Of the excised FELs, 198 (98%) were benign: fibroadenoma (FA) or benign breast tissue in 137 (68%), benign PT in 59 (29%), or LCIS in 2 (1%). Borderline PT or malignant lesions were found in 4 (2%). On ultrasound, malignant and borderline PTs were larger than benign lesions [median 3.9 vs 1.3 cm, p = 0.006]. Fifty FELs underwent AS, with a median follow-up of 17 (range 2-79) months. The majority remained stable or decreased in size: at 2 years, only 35% increased in volume by ≥ 50%. Of those tumors undergoing AS that were later excised (n = 4), all were benign. CONCLUSIONS: Almost all FELs (98%) were benign on surgical excision, and the majority undergoing AS remained stable, with benign pathology if later excised. Most FELs on NCB can be safely followed with US, with surgery reserved for patients with FELs that are large, symptomatic, or growing. This could spare most women with FELs unnecessary surgery.

Prepectoral Dual-Port Tissue Expander Placement: Can This Eliminate Suction Drain Use?

OBJECTIVES: The most common method of performing breast reconstruction after a mastectomy is using tissue expanders. Significant drainage that can lead to seromas and possible infection is a common sequela after mastectomies, and therefore, closed suction drains are routinely placed during the initial surgery (Vardanian et al. Plast Reconstr Surg. 2011;128:403-410). Drains, however, are associated with increased pain and discomfort for the patient and have been attributed to an increased infection rate by some authors (Degnim et al. Ann Surg. 2013;258:240-247; Saratzis et al. Clin Breast Cancer. 2009;9:243-246). We report on our experience using a dual-chamber tissue expander placed in the prepectoral space without acellular dermal matrix or other supportive material, which allows for drainage of periprosthetic fluid and avoids drain placement. PATIENTS AND METHODS: A retrospective, single-institution review of patients' records was performed for all patients who underwent prepectoral tissue expander placement between January 2018 and June 2019. Patients who had drains placed or who underwent autologous reconstruction in combination with expander placement were excluded. Thirty-nine patients were selected, with a total of 66 expander placements. Demographics including body mass index, comorbidities, history of smoking or steroid use, perioperative chemotherapy and radiation therapy, and intraoperative details and indications for surgery were retrospectively collected. Outcomes were separated into minor and major complications. Major complications were defined as complications that required surgical intervention. RESULTS: There were 51 prepectoral reconstructions with a dual-chamber tissue expander and no further surgical drain and 15 reconstructions using a standard expander with an additional closed suction drain. Overall complications for the no-drain cohort were 13.7% compared with 20% in the drain cohort (P = 0.68). Surgical site infection rate is 7.84% in the no-drain cohort compared with 13.3% in the drain cohort (P = 0.61). Mean numeric postoperative pain score at 6 hours was 3.2 in the no-drain cohort compared with 4.3 in the drain cohort (P = 0.03) and 4.17 compared with 5.6 at 12 hours, respectively (P = 0.04). Mean time to exchange of implant in the no-drain cohort was 152 days versus 126 days in the drain cohort (P = 0.38). Median follow-up times were 157 days for the no-drain cohort and 347 days for the drain cohort. CONCLUSIONS: Immediate breast reconstruction using a dual-chamber tissue expander offers a drain-free alternative to the immediate implant-based breast reconstruction. Our infection rate with 7.8% is lower than our own reported rates with subpectoral tissue expander reconstruction using either acellular dermal matrix or poly-4-hydroxybutyrate (17% and 11%). The overall complication rate is similar to historic data associated with breast reconstruction after mastectomy and suggests that dual-chamber expander placement offers a safe alternative possibly decreasing the patient's postoperative pain and discomfort that often is associated with closed suction drains (Saratzis et al. Clin Breast Cancer. 2009;9:243-246).

The impact of molecular subtype on breast cancer recurrence in young women treated with contemporary adjuvant therapy.

Breast cancer is the leading cause of cancer death in women younger than 40 years. Triple-negative breast cancer (TNBC) and human epidermal growth factor receptor-2 (HER2) positive subtypes have a particularly poor prognosis in this age group. The purpose of this study was to compare rates of recurrence among breast cancer subtypes in young patients treated with modern adjuvant systemic therapy. A retrospective review of breast cancer patients managed at a major academic breast center between May 2000 and November 2014 was performed. We included 239 women with breast cancer who were diagnosed and treated at age ≤40 years. Clinical, pathological, therapeutic, and outcome data were recorded. Patients were classified into the following molecular subtypes: luminal A/B (estrogen receptor [ER] positive and/or progesterone receptor [PR] positive, and HER2 negative), luminal/HER2 (ER positive and/or PR positive, and HER2 positive), HER2- enriched (ER negative, PR negative, and HER2 positive) and TNBC (ER negative, PR negative, and HER2 negative). Descriptive statistics were used to characterize the study cohort. Kaplan-Meier survival analysis was performed to estimate recurrence-free survival (RFS). Median follow-up time was 29 months. Mean age was 34.5 years. Among all patients, 193 (80.8%) were diagnosed with Invasive breast cancer and 46 (19.2%) with ductal carcinoma in situ with or without microinvasion. Subclassification into molecular subtypes was complete for 199 patients among which, 50.7% were classified as luminal A/B, 21.1% luminal/HER2, 12.1% HER2-enriched and 16.1% TNBC. Of the 199 patients, 25.1% received neo-adjuvant chemotherapy and 59.2% received adjuvant chemotherapy. Among HER2-positive patients, 81.3% received HER2 directed therapy. Twenty-eight patients (11.7%) had recurrences (13 loco-regional, seven distant, and eight both). At 3 years, the HER2 subtype had the highest RFS 100%, compared to 91.1% in luminal A/B, 85.6% in luminal/HER2 and 81.9% in TNBC. In comparing outcomes among subtypes, the HER2 positive subtype was associated with improved RFS, likely reflecting the impact of HER2 directed therapy. Those young patients with triple-negative subtype continued to have the poorest outcomes.

Association Between Recurrence and Re-Excision for Close and Positive Margins Versus Observation in Patients with Benign Phyllodes Tumors.

BACKGROUND: Breast lesions not sampled prior to surgery or initially diagnosed as fibroepithelial lesions on core biopsy may have a diagnosis of phyllodes tumor (PT) on excision. Historically, re-excision for close or positive margins has been the standard of care. We examined the rate of re-excision for close or positive margins in patients with benign phyllodes and compared recurrence rates among those undergoing re-excision versus observation. METHODS: We identified all patients with phyllodes tumor diagnosed between 2003 and 2013. Operative and surgical pathology reports were reviewed for clinical, pathologic, and follow-up data. RESULTS: Among 246 cases, 216 (88%) were benign PT and 30 (12%) borderline/malignant tumors. In the group of benign PT (n = 216), margins were negative in 64 patients (29.6%), 50 (23%) were close, and 102 (47%) were positive. Of those with close margins, 22 (44%) underwent reexcision and residual benign PT was found in 2 (9%). In patients with positive margins, 45 (44%) had re-excision and residual benign PT was detected in 4 (8.8%). After a median follow-up of 35.5 months, there were 4 (1.9%) recurrences among patients with benign PT. There was no difference in recurrence among patients who had re-excision for positive or close margins versus observation (p = 0.7 and 0.21, respectively). CONCLUSIONS: Among patients with close or positive margins, there was no significant difference in disease recurrence between patients who underwent reexcision and those who were observed. Based on these results, it may be reasonable to manage these patients conservatively with close follow-up.

Oncologic Outcomes After Nipple-Sparing Mastectomy.

BACKGROUND: Nipple-sparing mastectomy (NSM) is increasingly used as an alternative to traditional mastectomy because it provides improved aesthetic results. The data on its oncologic safety are limited. The authors' institution has performed NSM during the past 10 years for both oncologic and prophylactic indications. This study aimed to examine oncologic outcomes after NSM for breast cancer. METHODS: The study retrospectively examined all NSM cases managed between July 2007 and July 2013. Descriptive statistics were used to characterize the study cohort. Kaplan-Meier survival analysis was performed to estimate recurrence-free survival, specifically the 36-month recurrence-free survival proportion. RESULTS: A total of 721 nipple-sparing mastectomies were performed for 413 patients: 45 (10.9 %) to reduce risk and 368 (89.1 %) for breast cancer. In the breast cancer group, 29.8 % of the patients had ductal carcinoma in situ, and 70.2 % had invasive cancer. The mean follow-up time was 32 months (range 0.01-90.2 months). In the breast cancer group, the Kaplan-Meier 3-year recurrence-free survival rate was 93.6 % (95 % confidence interval, 89.9-96.0 %). Eight patients (2.2 %) had locoregional recurrences, including one in the nipple. Nine patients (2.4 %) had distant recurrence, and six patients (1.6 %) had a diagnosis of both local and distant recurrences. CONCLUSIONS: The findings showed a locoregional recurrence rate of 2.2 %, with an overall recurrence rate of 6.3 % for patients undergoing NSM for the treatment of breast cancer. The majority of these recurrences were distant, with one recurrence at the nipple. These results are promising, but a longer follow-up evaluation of this cohort is necessary.

A Phase II Trial Exploring the Success of Cryoablation Therapy in the Treatment of Invasive Breast Carcinoma: Results from ACOSOG (Alliance) Z1072.

BACKGROUND: Cryoablation is a well-established technique to treat fibroadenomas. Pilot studies suggest this could be an effective non-surgical treatment for breast cancer. American College of Surgeons Oncology Group Z1072 is a phase II trial exploring the effectiveness of cryoablation in the treatment of breast cancers. METHODS: The primary endpoint of Z1072 was the rate of complete tumor ablation, defined as no remaining invasive breast cancer (IBC) or ductal carcinoma in situ (DCIS) on pathologic examination of the targeted lesion. A secondary objective was to evaluate the negative predictive value of magnetic resonance imaging (MRI) to determine residual IBC or DCIS. Eligible patients included those with unifocal invasive ductal breast cancer ≤2 cm, with <25 % intraductal component and tumor enhancement on MRI. A total of 19 centers contributed 99 patients, of which 86 patients (87 breast cancers) were evaluable for data analysis. RESULTS: Final pathology results, regardless of whether residual IBC/DCIS was in the targeted ablation zone or elsewhere in the breast, showed successful ablation in 66/87 (75.9 %) cancers. The 90 % confidence interval for the estimate of successful cryoablation was 67.1-83.2, with the one-sided lower-sided 90 % CI of 69.0. The negative predictive value of MRI was 81.2 % (90 % CI 71.4-88.8). When multifocal disease outside of the targeted cryoablation zone was not defined as an ablation failure, 80/87 (92 %) of the treated cancers had a successful cryoablation. CONCLUSION: Further studies with modifications on the Z1072 protocol could be considered to evaluate the role for cryoablation as a non-surgical treatment of early-stage breast cancer.

A randomized prospective study of lumpectomy margin assessment with use of MarginProbe in patients with nonpalpable breast malignancies.

BACKGROUND: The presence of tumor cells at the margins of breast lumpectomy specimens is associated with an increased risk of ipsilateral tumor recurrence. Twenty to 30 % of patients undergoing breast-conserving surgery require second procedures to achieve negative margins. This study evaluated the adjunctive use of the MarginProbe device (Dune Medical Devices Ltd, Caesarea, Israel) in providing real-time intraoperative assessment of lumpectomy margins. METHODS: This multicenter randomized trial enrolled patients with nonpalpable breast malignancies. The study evaluated MarginProbe use in addition to standard intraoperative methods for margin assessment. After specimen removal and inspection, patients were randomized to device or control arms. In the device arm, MarginProbe was used to examine the main lumpectomy specimens and direct additional excision of positive margins. Intraoperative imaging was used in both arms; no intraoperative pathology assessment was permitted. RESULTS: In total, 596 patients were enrolled. False-negative rates were 24.8 and 66.1 % and false-positive rates were 53.6 and 16.6 % in the device and control arms, respectively. All positive margins on positive main specimens were resected in 62 % (101 of 163) of cases in the device arm, versus 22 % (33 of 147) in the control arm (p < 0.001). A total of 19.8 % (59 of 298) of patients in the device arm underwent a reexcision procedure compared with 25.8 % (77 of 298) in the control arm (6 % absolute, 23 % relative reduction). The difference in tissue volume removed was not significant. CONCLUSIONS: Adjunctive use of the MarginProbe device during breast-conserving surgery improved surgeons' ability to identify and resect positive lumpectomy margins in the absence of intraoperative pathology assessment, reducing the number of patients requiring reexcision. MarginProbe may aid performance of breast-conserving surgery by reducing the burden of reexcision procedures for patients and the health care system.

An unusual breast lesion: granular cell tumor of the breast with extensive chest wall invasion.

Granular cell tumors (GCT) are generally benign soft tissue tumors. When located in the breast, they may be misdiagnosed as more typical tumors, such as invasive ductal carcinoma, based on misleading clinical or radiologic features. GCTs are frequently found in the setting of a known malignancy. We report the case of a patient with a large infra-mammary fold GCT, the management of which required a multidisciplinary operative approach due to extensive chest wall invasion.

Impact of the COVID-19 breast cancer screening hiatus on clinical stage and racial disparities in New York City.

BACKGROUND: The impact of the COVID-19 mammography screening hiatus as well as of post-hiatus efforts promoting restoration of elective healthcare on breast cancer detection patterns and stage distribution is unknown. METHODS: Newly diagnosed breast cancer patients (2019-2021) at the New York Presbyterian (NYP) Hospital Network were analyzed. Chi-square and student's t-test compared characteristics of patients presenting before and after the screening hiatus. RESULTS: A total of 2137 patients were analyzed. Frequency of screen-detected and early-stage breast cancer declined post-hiatus (59.7%), but returned to baseline (69.3%). Frequency of screen-detected breast cancer was lowest for African American (AA) (57.5%) and Medicaid patients pre-hiatus (57.2%), and this disparity was reduced post-hiatus (65.3% for AA and 63.2% for Medicaid). CONCLUSIONS: The return to baseline levels of screen-detected cancer, particularly among AA and Medicaid patients suggest that large-scale breast health education campaigns may be effective in resuming screening practices and in mitigating disparities.

Clinical Utility of Universal Germline Genetic Testing for Patients With Breast Cancer.

Importance: National Comprehensive Cancer Network guidelines currently recommend germline testing for high-risk genes in selected patients with breast cancer. The clinical utility of recommending testing all patients with breast cancer with multigene panels is currently under consideration. Objective: To examine the implications of universal testing of patients with breast cancer with respect to clinical decision-making. Design, Setting, and Participants: Patients from a previously reported cohort were assessed as in-criteria or out-of-criteria according to the 2017 guidelines and underwent testing with a multigene germline panel between 2017 to 2018. Patients were women and men aged 18 to 90 years, with a new and/or previous diagnosis of breast cancer who had not undergone either single or multigene testing. Clinicians from 20 community and academic sites documented patient clinical information and changes to clinical recommendations made according to test findings. Association between prevalence of pathogenic or likely pathogenic germline variants and previously unreported clinical features, including scores generated by the BRCAPRO statistical model, was determined. Data were analyzed from April 2020 to May 2022. Exposure: New and/or previous diagnosis of breast cancer. Main Outcomes and Measures: Disease management recommendations that were changed as a result of genetic testing results are reported. Results: Clinicians were asked to assess changes to clinical management as a result of germline genetic testing for 952 patients. Informative clinician-reported recommendations were provided for 939 (467 in-criteria and 472 out-of-criteria) of the patients with breast cancer (936 [99.7%] female; 702 [74.8%] White; mean [SD] age at initial diagnosis, 57.6 [11.5] years). One or more changes were reported for 31 of 37 (83.8%) in-criteria patients and 23 of 34 (67.6%) out-of-criteria patients with a pathogenic or likely pathogenic variant. Recommendations were changed as a result of testing results for 14 of 22 (63.6%) out-of-criteria patients who had a variant in a breast cancer predisposition gene. Clinicians considered testing beneficial for two-thirds of patients with pathogenic or likely pathogenic variants and for one-third of patients with either negative results or variants of uncertain significance. There was no difference in variant rate between patients meeting the BRCAPRO threshold (≥10%) and those who did not (P = .86, Fisher exact test). No changes to clinical recommendations were made for most patients with negative results (345 of 349 patients [98.9%]) or variants of uncertain significance (492 of 509 patients [96.7%]). Conclusions and Relevance: In this cohort study, germline genetic testing was used by clinicians to direct treatment for most out-of-criteria patients with breast cancer with pathogenic or likely pathogenic germline variants, including those with moderate-risk variants. Universal germline testing informs clinical decision-making and provides access to targeted treatments and clinical trials for all patients with breast cancer.

Screening mammography mitigates breast cancer disparities through early detection of triple negative breast cancer.

PURPOSE: Screening mammography improves breast cancer survival through early detection, but Triple Negative Breast Cancer (TNBC) is more difficult to detect on mammography and has lower survival compared to non-TNBC, even when detected at early stages. TNBC is twice as common among African American (AA) compared to White American (WA) women, thereby contributing to the 40% higher breast cancer mortality rates observed in AA women. The role of screening mammography in addressing breast cancer disparities is therefore worthy of study. METHODS: Outcomes were evaluated for TNBC patients treated in the prospectively-maintained databases of academic cancer programs in two metropolitan cities of the Northeast and Midwest, 1998-2018. RESULTS: Of 756 TNBC cases, 301 (39.8%) were mammographically screen-detected. 46% of 189 AA and 38.5% of 460 WA patients had screen-detected TNBC (p = 0.16). 25.3% of 257 TNBC cases ≤50 years old had screen-detected disease compared to 47.3% of 499 TNBC cases >50 years old (p < 0.0001). 220/301 (73.1%) screen-detected TNBC cases were T1 lesions versus 118/359 (32.9%) non-screen-detected cases (p < 0.0001). Screen-detected TNBC was more likely to be node-negative (51.9% v. 40.4%; p < 0.0001). Five-year overall survival was better in screen-detected TNBC compared to nonscreen-detected TNBC (92.8% v. 81.5%; p < 0.0001) in the entire cohort. The magnitude of this effect was most significant among AA patients (Fig. 1). Screening-related survival patterns were similar among AA and WA patients in both cities. CONCLUSION: Data from two different cities demonstrates the value of screening mammography to mitigate breast cancer disparities in AA women through the early detection of TNBC.

Nipple-areolar complex-sparing mastectomy: feasibility, patient selection, and technique.

BACKGROUND: We assessed the feasibility, patient selection, and technique of nipple-areolar complex (NAC)-sparing mastectomy. This dynamic article includes a video that demonstrates that sentinel node biopsy or axillary dissection can be performed through the mastectomy incisions or through a separate axillary incision. METHODS: The University of Texas M. D. Anderson Cancer Center initiated a prospective study investigating the feasibility of performing NAC-sparing mastectomy in the setting of prophylaxis and breast cancer treatment. Patients selected were at low risk for skin/NAC necrosis and NAC involvement with tumor. RESULTS: Preliminary results of 54 breasts that underwent NAC-sparing mastectomy showed a NAC necrosis rate of 7.2%. One patient who underwent NAC-sparing prophylactic mastectomy was found to have ductal carcinoma-in-situ that was not present at the nipple base. At a median follow-up of 15 months, there has been no NAC recurrence, which is similar to other reported series of 0% to 2%. Results were comparable with other small prospective series. CONCLUSIONS: NAC-sparing mastectomy can be performed effectively while maintaining NAC viability. The risk of leaving residual breast tissue or occult tumor with the NAC is probably low if margin assessment is performed at the base or central core of the NAC. Long-term follow-up is forthcoming on these procedures. To achieve optimal cosmetic results with oncologic safety, NAC-sparing mastectomy should only be performed in carefully selected patients.

Underdiagnosis of Hereditary Breast Cancer: Are Genetic Testing Guidelines a Tool or an Obstacle?

PURPOSE: An estimated 10% of breast and ovarian cancers result from hereditary causes. Current testing guidelines for germ line susceptibility genes in patients with breast carcinoma were developed to identify carriers of BRCA1/ 2 variants and have evolved in the panel-testing era. We evaluated the capability of the National Comprehensive Cancer Network (NCCN) guidelines to identify patients with breast cancer with pathogenic variants in expanded panel testing. METHODS: An institutional review board-approved multicenter prospective registry was initiated with 20 community and academic sites experienced in cancer genetic testing and counseling. Eligibility criteria included patients with a previously or newly diagnosed breast cancer who had not undergone either single- or multigene testing. Consecutive patients 18 to 90 years of age were consented and underwent an 80-gene panel test. Health Insurance Portability and Accountability Act-compliant electronic case report forms collected information on patient demographics, diagnoses, phenotypes, and test results. RESULTS: More than 1,000 patients were enrolled, and data records for 959 patients were analyzed; 49.95% met NCCN criteria, and 50.05% did not. Overall, 8.65% of patients had a pathogenic/likely pathogenic (P/LP) variant. Of patients who met NCCN guidelines with test results, 9.39% had a P/LP variant. Of patients who did not meet guidelines, 7.9% had a P/LP variant. The difference in positive results between these groups was not statistically significant (Fisher's exact test P = .4241). CONCLUSION: Our results indicate that nearly half of patients with breast cancer with a P/LP variant with clinically actionable and/or management guidelines in development are missed by current testing guidelines. We recommend that all patients with a diagnosis of breast cancer undergo expanded panel testing.

Sentinel node positivity rates with and without frozen section for breast cancer.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is used to detect breast cancer axillary metastases. Some surgeons send the sentinel lymph node (SLN) for intraoperative frozen section (FS) to minimize delayed axillary dissections. There has been concern that FS may discard nodal tissue and thus underdiagnose small metastases. This study examines whether evaluation of SLN by FS increases the false-negative rate of SLNB. METHODS: A retrospective analysis of SLNB from 659 patients was conducted to determine the frequency of node positivity among SLNB subjected to both FS and permanent section (PS) versus PS alone. Statistical analysis was performed by the chi(2) square test, and a logistic regression model was applied to estimate the effect of final node positivity between the two groups. RESULTS: FS was performed in 327 patients and PS was performed in all 659 patients. Among patients undergoing both FS and PS (n = 327), the final node positivity rate was 33.0% compared with 19.6% among patients undergoing PS alone (n = 332). After adjustment for patient age, tumor diameter, grade, and hormone receptor status in a multivariate logistic regression model, there remained an increased likelihood of final node positivity for patients undergoing both procedures relative to PS alone (adjusted odds ratio, 2.1; 95% confidence interval, 1.3-3.6; P = .005). CONCLUSIONS: There was a higher rate of SLN positivity in specimens evaluated by both FS and PS. Therefore, evaluating SLN by FS does not underdiagnose small metastases nor produce a higher false-negative rate. Intraoperative FS offers the advantage of less delayed axillary dissections.