Participation in a High-Risk Program Is Associated with a Diagnosis of Earlier-Stage Disease Among Women at Increased Risk for Breast Cancer Development.

BACKGROUND: High-risk programs provide recommendations for surveillance/risk reduction for women at elevated risk for breast cancer development. This study evaluated the impact of high-risk surveillance program participation on clinicopathologic breast cancer features at the time of diagnosis. METHODS: Women followed in the authors' high-risk program (high-risk cohort [HRC]) with a diagnosis of breast cancer from January 2015 to June 2021 were identified and compared with the general population of women undergoing breast cancer surgery at Memorial Sloan Kettering Cancer Center (MSK; general cohort [GC]) during the same period. Patient and tumor factors were collected. Clinicopathologic features were compared between the two cohorts and in a subset of women with a family history of known BRCA mutation. RESULTS: The study compared 255 women in the HRC with 9342 women in the GC. The HRC patients were slightly older and more likely to be white and have family history than the GC patients. The HRC patients also were more likely to present with DCIS (41 % vs 23 %; p < 0.001), to have smaller invasive tumors (pT1: 100 % vs 77 %; p < 0.001), and to be pN0 (95 % vs 81 %; p < 0.001). The HRC patients had more invasive triple-negative tumors (p = 0.01) and underwent less axillary surgery (p < 0.001), systemic therapy (p < 0.001), and radiotherapy (p = 0.002). Among those with a known BRCA mutation, significantly more women in the HRC underwent screening mammography (75 % vs 40 %; p < 0.001) or magnetic resonance imaging (MRI: 82 % vs 9.9 %; p < 0.001) in the 12 months before diagnosis. CONCLUSIONS: Women followed in a high-risk screening program have disease diagnosed at an earlier stage and therefore require less-intensive breast cancer treatment than women presenting to a cancer center at the time of diagnosis. Identification of high-risk women and implementation of increased surveillance protocols are vital to improving outcomes.

Financial Toxicity Among Women with Breast Cancer Varies by Age and Race.

INTRODUCTION: Financial toxicity negatively affects clinical outcomes in breast cancer. Underrepresented demographics may be at higher risk for financial toxicity. We characterized disparities on the basis of age and other factors. PATIENTS AND METHODS: Surveys completed by women with stage 0-IV breast cancer treated at Memorial Sloan Kettering Cancer Center between 06/2022 and 05/2023 were analyzed. The comprehensive score for financial toxicity (COST) scale was used to assess financial toxicity. Descriptive statistics were calculated for differences in financial toxicity/related factors, and outcomes by age and race. Associations between variables of interest and COST scores were analyzed using linear regression. RESULTS: Of 8512 respondents (75% white, 9.3% Asian, 8.4% Black), most (68%) had clinical stage 0/I disease. Stratified by age, young Black women had higher financial toxicity than young white or Asian women (p < 0.001). On multivariable analysis, women age < 45 years experienced higher financial toxicity than older women (coefficient - 2.0, 95% CI - 2.8 to - 1.1, p < 0.001). Compared with white women, financial toxicity was greater among Black (coefficient - 6.8, 95% CI - 7.8 to - 5.8) and Asian women (coefficient - 3.5, 95% CI - 4.4 to - 2.5). Cost-related medication non-adherence was more frequent among Black and Asian women (p < 0.001). Asian women more often paid for treatment with savings than white and Black women (p < 0.001). Young women reported using savings for treatment-related costs more than older (45% vs. 32%); p < 0.001). CONCLUSIONS: Racial minorities and young patients are disproportionately affected by financial toxicity. Further studies are planned to determine how financial toxicity evolves over time and whether referral to financial services effectively reduces toxicity.

Do HER2-Low Tumors Have a Distinct Clinicopathologic Phenotype?

BACKGROUND: Breast cancer subtypes, distinguished by hormone receptor (HR) and HER2 status, have different clinicopathologic features. With recognition of the clinical relevance of HER2-low, there is debate as to whether this is a distinct subtype. Our study aimed to determine whether HER2-low breast cancers have specific clinicopathologic features that differ from those of HER2-negative and HER2-positive cancers. PATIENTS AND METHODS: A total of 11,072 patients undergoing upfront surgery from 1998 to 2010 were identified from a single-institution prospectively maintained database. HER2 status was classified by immunohistochemistry (IHC)/fluorescence in situ hybridization (FISH) as HER2 negative (41.2%), HER2 low (45%; IHC 1+ or 2+ with negative FISH), and HER2 positive (13.7%), and stratified by HR status. Univariate (UVA) and multivariable multinomial logistic regression analysis (MVA) were performed to determine associations among variables and subtypes. RESULTS: Compared with HER2-negative tumors, HER2 low was associated with lymphovascular invasion [odds ratio (OR) 1.2, 95% confidence interval (CI) 1.06-1.36; p = 0.003], multifocality (OR 1.26, 95% CI 1.12-1.42; p < 0.001), nodal micrometastasis (OR 1.15, 95% CI 1.02-1.31; p = 0.024), and lower rates of ≥ 3 positive nodes (OR 0.77, 95% CI 0.66-0.90, p = 0.001). When stratified by HR expression, in both HR-positive and HR-negative tumors, age and multifocality were associated with HER2 low on UVA. On MVA, no variables were independently associated with both HR-negative and HR-positive/HER2-low tumors compared with HER2-negative tumors. In contrast, HER2-positive tumors, regardless of HR status, were associated with multifocality and an extensive intraductal component. CONCLUSION: Clinicopathologic features of HER2-low tumors appear to be primarily related to HR status. Our findings do not support the characterization of HER2 low as a separate subtype.

Examining Race and Patient-Reported Outcomes After Contralateral Prophylactic Mastectomy with Reconstruction.

BACKGROUND: Little is known regarding racial differences in satisfaction and quality of life (QOL) after contralateral prophylactic mastectomy (CPM). In this study, we aim to characterize associations between race, and postoperative satisfaction and well-being, utilizing the validated BREAST-Q patient-reported outcome measure. PATIENTS AND METHODS: Patients were eligible if they were diagnosed with stage 0-III unilateral breast cancer and underwent mastectomy with immediate reconstruction at our institution between 2016 and 2022. BREAST-Q surveys were administered in routine clinical care preoperatively and postoperatively to assess QOL. We assessed whether the relationship between race, and domains of satisfaction with breasts and psychosocial well-being differed by receipt of CPM compared with unilateral mastectomy at 6 months, 1 year, 2 years, and 3 years following reconstruction. RESULTS: Of 3334 women, 2040 (61%) underwent unilateral mastectomy and 1294 (39%) underwent CPM. Compared with White and Asian women who received CPM, Black women who underwent CPM were more likely to have higher BMI (p < 0.001), undergo autologous reconstruction (p = 0.006), and receive postmastectomy radiation (PMRT) (p < 0.001). There was no association between race and domains of satisfaction of breasts or psychosocial well-being for women who underwent unilateral mastectomy (p = 0.6 and p > 0.9, respectively) or CPM (p = 0.8 and p = 0.9, respectively). PMRT was negatively associated with both satisfaction with breasts (p < 0.001) and psychosocial well-being (p = 0.007). CONCLUSIONS: Differences in satisfaction with breasts and psychosocial well-being at 3-year follow-up were not associated with race but rather treatment variables, particularly the receipt of PMRT. Further investigations with a larger and more diverse population are needed to validate these findings.

Patient-Reported Outcomes in Patients Undergoing Lumpectomy With and Without Defect Closure.

BACKGROUND: The effect of lumpectomy defect repair (a level 1 oncoplastic technique) on patient-reported breast satisfaction among patients undergoing lumpectomy has not yet been investigated. METHODS: Patients undergoing lumpectomy at our institution between 2018 and 2020 with or without repair of their lumpectomy defect during index operation, comprised our study population. The BREAST-Q quality-of-life questionnaire was administered preoperatively, and at 6 months, 1 year, and 2 years postoperatively. Satisfaction and quality-of-life domains were compared between those who did and did not have closure of their lumpectomy defect, and compared with surgeon-reported outcomes. RESULTS: A total of 487 patients met eligibility criteria, 206 (42%) had their partial mastectomy defect repaired by glandular displacement. Median breast volume, as calculated from the mammogram, was smaller in patients undergoing defect closure (826 cm3 vs. 895 cm3, p = 0.006). There were no statistically significant differences in satisfaction with breasts (SABTR), physical well-being of the chest (PWB-CHEST), or psychosocial well-being (PsychWB) scores between the two cohorts at any time point. While patients undergoing defect closure had significantly higher sexual well-being (SexWB) scores compared with no closure (66 vs. 59, p = 0.021), there were no predictors of improvement in SexWB scores over time on multivariable analysis. Patients' self-reported scores positively correlated with physician-reported outcomes. CONCLUSIONS: Despite a larger lumpectomy-to-breast volume ratio among patients undergoing defect repair, satisfaction was equivalent among those whose defects were or were not repaired at 2 years postsurgery. Defect repair was associated with clinically relevant improvement in patient-reported sexual well-being.

Impact of Neoadjuvant Chemoimmunotherapy on Surgical Outcomes and Time to Radiation in Triple-Negative Breast Cancer.

BACKGROUND: We examined the association between immunotherapy-containing and standard chemotherapy regimens with treatment delays and postoperative complications in stage II-III triple-negative breast cancer. The effect of immune-related adverse events (irAEs) was compared. PATIENTS AND METHODS: We compared 139 women treated with neoadjuvant pembrolizumab plus chemotherapy (KEYNOTE-522 regimen) from August 2021 to September 2022 with 287 consecutive patients who received neoadjuvant chemotherapy alone prior to July 2021 and underwent surgery. Baseline characteristics, time to treatments, and surgical complications were compared using two-sample non-parametric tests. Linear regression evaluated association of irAEs with time to surgery and radiation. Logistic regression identified factors associated with surgical complications. RESULTS: Age, body mass index, race, American Society of Anesthesiologists (ASA) class, and mastectomy rates were similar among cohorts. No clinically relevant difference in time from end of neoadjuvant treatment to surgery was observed [KEYNOTE-522: median 32 (IQR 27, 43) days; non-KEYNOTE-522: median 31 (IQR 26, 37) days; P = 0.048]. Time to radiation did not differ (P = 0.7). A total of 26 patients (9%; non-KEYNOTE-522) versus 11 (8%; KEYNOTE-522) experienced postoperative complications (P = 0.6). In the KEYNOTE-522 cohort, 59 (43%) of 137 patients experienced 82 irAEs; 40 (68%) required treatment. Older age (P = 0.018) and ASA class 4 (P = 0.007) were associated with delays to surgery after adjusting for clinical factors. Experiencing ≥ 1 irAE was associated with delay to radiation (P = 0.029). IrAEs were not associated with surgical complications (P = 0.4). CONCLUSIONS: We observed no clinically meaningful difference between times to surgery/adjuvant radiation or postoperative complications and type of preoperative chemotherapy. IrAEs were associated with delay to adjuvant radiation but not with postoperative complications or delay to surgery.

Impact of Mastectomy Flap Necrosis on Patient-Reported Quality-of-Life Measures After Nipple-Sparing Mastectomy: A Preliminary Analysis.

BACKGROUND: Mastectomy skin flap necrosis (SFN) is common following nipple-sparing mastectomy (NSM), but studies on its quality-of-life (QOL) impact are limited. We examined patient-reported QOL and satisfaction after NSM with/without SFN utilizing the BREAST-Q patient-reported outcome measure (PROM) survey. PATIENTS AND METHODS: Patients undergoing NSM between April 2018 and July 2021 at our institution were examined; the BREAST-Q PROM was administered preoperatively, and at 6 months and 1 year postoperatively. SFN extent/severity was documented at 2-3 weeks postoperatively; QOL and satisfaction domains were compared between patients with/without SFN. RESULTS: A total of 573 NSMs in 333 patients were included, and 135 breasts in 82 patients developed SFN (24% superficial, 56% partial thickness, 16% full thickness). Patients with SFN reported significantly lower scores in the satisfaction with breasts (p = 0.032) and psychosocial QOL domains (p = 0.009) at 6 months versus those without SFN, with scores returning to baseline at 1 year in both domains. In the "physical well-being-of-the-chest" domain, there was an overall decline in scores among all patients; however, there were no significant differences at any time point between patients with or without SFN. Sexual well-being scores declined for patients with SFN compared with those without at 6 months and also at 1 year, but this did not reach significance (p = 0.13, p = 0.2, respectively). CONCLUSIONS: Patients undergoing NSM who developed SFN reported significantly lower satisfaction and psychosocial well-being scores at 6 months, which returned to baseline by 1 year. Physical well-being of the chest significantly declines after NSM regardless of SFN. Future studies with larger sample sizes and longer follow-up are needed to determine SFN's impact on long-term QOL.

Do non-classic invasive lobular carcinomas derive a benefit from neoadjuvant chemotherapy?

PURPOSE: Invasive lobular breast cancers (ILCs) respond poorly to neoadjuvant chemotherapy (NAC). The degree of benefit of NAC among non-classic ILC (NC-ILC) variants compared with classic ILCs (C-ILCs) is unknown. METHODS: Consecutive patients with Stage I-III ILC treated from 2003 to 2019 with NAC and surgery were identified, and grouped as C-ILC or NC-ILC as per the original surgical pathology report, with pathologist (A.G.) review performed if original categorization was unclear. A subset of similarly treated invasive ductal cancers (IDCs) was identified for comparison. Clinicopathologic characteristics and pathologic complete response (pCR) rates were evaluated. RESULTS: Of 145 patients with ILC, 101 (70%) were C-ILC and 44 (30%) were NC-ILC (IDC cohort: 1157 patients). ILC patients were older, more often cT3/T4 and cN2/N3, and less often high-grade compared to IDC patients. Those with NC-ILC were less often ER+/HER2- (55% versus 93%), and more often HER2 + (25% versus 7%) and TN (21% versus 0%, all p < 0.001). Breast pCR was more common among NC-ILC, but most frequent in IDC. Nodal pCR rates were also lowest among C-ILC patients, but similar among NC-ILC and IDC patients. On multivariable analysis, C-ILC (OR 0.09) and LVI (OR 0.51) were predictive of lack of breast pCR; non-ER+/HER2- subtypes and breast pCR were predictive of nodal pCR. When our analysis was repeated with patients stratified by receptor subtype, histology was not independently predictive of either breast or nodal pCR. CONCLUSION: NC-ILC patients were significantly more likely to achieve breast and nodal pCR compared with C-ILC patients, but when stratified by subtype, histology was not independently predictive of breast or nodal pCR.

Contrast-enhanced mammography in the assessment of residual disease after neoadjuvant treatment.

PURPOSE: To investigate the utility of contrast-enhanced mammography (CEM) as an alternative to breast MRI for the evaluation of residual disease after neoadjuvant treatment (NAT). METHODS: This prospective study enrolled consecutive women undergoing NAT for breast cancer from July 2017-July 2019. Breast MRI and CEM exams performed after completion of NAT were read independently by two breast radiologists. Residual disease and lesion size on MRI and CEM recombined (RI) and low-energy images (LEI) were compared. Histopathology was considered the reference standard. Statistical analysis was performed using McNemar's and Leisenring's tests. Multiple comparison adjustment was made using Bonferroni procedure. Lesion sizes were correlated using Kendall's tau coefficient. RESULTS: There were 110 participants with 115 breast cancers. Residual disease (invasive cancer or ductal carcinoma in situ) was detected in 83/115 (72%) lesions on pathology, 71/115 (62%) on MRI, 55/115 (48%) on CEM RI, and 75/115 (65%) on CEM LEI. When using multiple comparison adjustment, no significant differences were detected between MRI combined with CEM LEI and CEM RI combined with CEM LEI, in terms of accuracy (MRI: 77%, CEM: 72%; p ≥ 0.99), sensitivity (MRI: 88%, CEM: 81%; p ≥ 0.99), specificity (MRI: 47%, CEM: 50%; p ≥ 0.99), PPV (MRI: 81%, CEM: 81%; p ≥ 0.99), or NPV (MRI: 60%, CEM: 50%; p ≥ 0.99). Size correlation between pathology and both MRI combined with CEM LEI and CEM RI combined with CEM LEI was moderate: τ = 0. 36 vs 0.33 (p ≥ 0.99). CONCLUSION: Contrast-enhanced mammography is an acceptable alternative to breast MRI for the detection of residual disease after neoadjuvant treatment.

Axillary Staging Is Not Justified in Postmenopausal Clinically Node-Negative Women Based on Nodal Disease Burden.

BACKGROUND: RxPONDER showed no benefit of adjuvant chemotherapy in postmenopausal women with estrogen receptor (ER) positive/human epidermal growth factor receptor 2 (HER2) negative breast cancer and limited nodal burden (pN1) with a recurrence score ≤ 25, suggesting that axillary staging could be omitted in cN0 patients if significant numbers of such women do not have pN2-3 disease. Here we evaluate the pN2-3 disease rate in a large cohort of postmenopausal women presenting with cN0 breast cancer. PATIENTS AND METHODS: Consecutive postmenopausal patients presenting with T1-2N0 breast cancer who underwent axillary surgery from February 2006 to December 2011 were identified. Clinicopathologic characteristics associated with pN2-3 disease were examined using chi-square or Fisher's exact tests. RESULTS: Of 3363 postmenopausal women with cT1-2N0 breast cancer (median age 58 years, IQR 48-67 years), median tumor size was 1.3 cm (IQR 0.90-1.90cm). Post-axillary staging, 2600 (77.3%) were pN0, 643 (19.1%) were pN1, and 120 (3.6%) were pN2-3. The pN2-3 disease rate did not differ across subtypes (4.4% HER2+, 3.5% HR-/HER2-, 3.5% HR+/HER2-, p = 0.70). In the subset with HR+/HER2- tumors, on multivariable analysis, age < 65 years (odds ratio [OR] 2.38, 95% confidence interval [CI] 1.32-4.49), lymphovascular invasion (OR 5.29, 95% CI 2.72-11.2), multifocal/centric tumors (OR 3.08, 95% CI 1.79-5.32), and tumor size > 2 cm (OR 5.51, 95% CI 3.05-10.4) were significantly associated with pN2-3 nodal burden. Of 506 patients with tumors > 2 cm, 49 (9.7%) had pN2-3 disease; in the subset of 90 patients age < 65 years who had multifocal/centric tumors > 2 cm, 23 (25.6%) had pN2-3 disease. CONCLUSIONS: In postmenopausal women with cN0 disease, pN2-3 nodal burden is uncommon; omitting axillary staging would not miss a significant number of patients who might benefit from adjuvant chemotherapy. Information available preoperatively indicating a higher risk of nodal disease such as younger age and large, multifocal tumors should be considered in the multidisciplinary management of the axilla.

The Impact of Breast-Conserving Surgery Re-excision on Patient-Reported Outcomes Using the BREAST-Q.

BACKGROUND: Approximately 14% of women undergoing breast-conserving surgery (BCS) require re-excision to achieve negative margins following the Society of Surgical Oncology (SSO) and American Society for Radiation Oncology (ASTRO) margin guidelines, which may influence patient-reported outcomes (PROs). Few studies have assessed the impact of re-excision on PROs following BCS. PATIENTS AND METHODS: Women with stage 0-III breast cancer undergoing BCS who completed a BREAST-Q PRO measure from 2010 to 2016 were identified from a prospective database. Baseline characteristics were compared between women who underwent one BCS and those who underwent ≥ 1 re-excision surgery for positive margins (R-BCS). Linear mixed models were used to analyze associations between number of excisions and BREAST-Q scores over time. RESULTS: Of 2543 eligible women, 1979 (78%) had one BCS and 564 (22%) had R-BCS. Younger age, lower BMI, surgery pre-SSO Invasive Guidelines issuance, ductal carcinoma in situ (DCIS), multifocal disease, radiation therapy receipt, and endocrine therapy omission were more common in the R-BCS group. Breast satisfaction and sexual well-being were lower in the R-BCS group 2 years postoperatively. There were no differences in psychosocial well-being between groups over 5 years. On multivariable analysis, re-excision was associated with lower breast satisfaction and sexual well-being (p= 0.007 and p= 0.049, respectively), but there was no difference in psychosocial well-being (p= 0.250). CONCLUSIONS: Women with R-BCS had lower breast satisfaction and sexual well-being 2 years postoperatively, but this difference did not remain long term. Psychosocial well-being in women who underwent one BCS were largely comparable over time to the R-BCS group. These findings may help in counseling women who are concerned about satisfaction and quality-of-life outcomes with BCS if re-excision is necessary.

Is Surgical Excision of Focal Atypical Ductal Hyperplasia Warranted? Experience at a Tertiary Care Center.

BACKGROUND: The core-needle biopsy (CNB) diagnosis of atypical ductal hyperplasia (ADH) generally mandates follow-up excision, but controversy exists on whether small foci of ADH require surgical management. This study evaluated the upgrade rate at excision of focal ADH (fADH), defined as 1 focus spanning ≤ 2 mm. METHODS: We retrospectively identified in-house CNBs with ADH as the highest-risk lesion obtained between January 2013 and December 2017. A radiologist assessed radiologic-pathologic concordance. All CNB slides were reviewed by two breast pathologists, and ADH was classified as fADH and nonfocal ADH based on extent. Only cases with follow-up excision were included. The slides of excision specimens with upgrade were reviewed. RESULTS: The final study cohort consisted of 208 radiologic-pathologic concordant CNBs, including 98 fADH and 110 nonfocal ADH. The imaging targets were calcifications (n = 157), a mass (n = 15), nonmass enhancement (n = 27), and mass enhancement (n = 9). Excision of fADH yielded seven (7%) upgrades (5 ductal carcinoma in situ (DCIS), 2 invasive carcinoma) versus 24 (22%) upgrades (16 DCIS, 8 invasive carcinoma) at excision of nonfocal ADH (p = 0.01). Both invasive carcinomas found at excision of fADH were subcentimeter tubular carcinomas away from the biopsy site and deemed incidental. CONCLUSIONS: Our data show a significantly lower upgrade rate at excision of focal ADH than nonfocal ADH. This information can be valuable if nonsurgical management of patients with radiologic-pathologic concordant CNB diagnosis of focal ADH is being considered.

Timing of Chemotherapy and Patient-Reported Outcomes After Breast-Conserving Surgery and Mastectomy with Immediate Reconstruction.

INTRODUCTION: Receipt of chemotherapy is associated with decreased satisfaction after breast surgery, but whether timing as adjuvant versus neoadjuvant (NAC) affects patient-reported outcomes (PROs) is unclear. We examined associations between chemotherapy timing and PROs after breast-conserving surgery (BCS) and mastectomy with immediate reconstruction (M-IR). METHODS: In this retrospective cohort study of patients with stage I-III breast cancer undergoing chemotherapy between January 2017 and December 2019, we compared satisfaction with breasts (SABTR) and chest physical well-being (PWB-CHEST) between chemotherapy groups in BCS and M-IR cohorts. Median SABTR and PWB-CHEST scores (scale 0-100) were compared between chemotherapy groups at baseline and for 3 years postoperatively. Factors associated with SABTR and PWB-CHEST at 1 and 2 years were assessed with multivariable linear regression. RESULTS: Overall, 640 patients had BCS and 602 had M-IR; 210 (33%) BCS patients and 294 (49%) M-IR patients had NAC. Following BCS, SABTR was higher than baseline at all postoperative timepoints, whereas 3-year SABTR remained similar to baseline following M-IR, independent of chemotherapy timing. In both surgical cohorts, PWB-CHEST was lowest after NAC at 6 months compared with baseline but was similar to adjuvant counterparts by 3 years. NAC was not a statistically significant predictor of SABTR or PWB-CHEST in either surgical cohort on multivariable analysis. CONCLUSIONS: For patients with breast cancer who require chemotherapy, neoadjuvant versus adjuvant timing does not impact long-term PROs in this study. These findings may inform shared decision making regarding the sequence of treatment in patients with operable disease.

Mutational Status is Associated with a Higher Rate of Pathologic Complete Response After Neoadjuvant Chemotherapy in Hormone Receptor-Positive Breast Cancer.

BACKGROUND: Pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) occurs in up to 20% of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancers. Whether this differs among BRCA mutation carriers is uncertain. This study compared pCR between BRCA1/2 mutation carriers and matched sporadic control subjects. METHODS: From November 2013 to January 2022, this study identified 522 consecutive women with clinical stage I to III HR+/HER2- breast cancer treated with NAC and surgery. The study matched BRCA1/2 mutation carriers 1:2 to non-carriers in terms of age, clinical tumor (cT) and nodal (cN) stage, and differentiation. Two-sample non-parametric tests compared baseline characteristics. Multivariable logistic regression assessed pCR (i.e., ypT0/ispN0) by BRCA1/2 mutational status. RESULTS: Of the 522 women (median age, 50 years), 59 had BRCA1/2 mutations, 78% of which were clinically node positive. Anthracycline-based NAC was administered to 97%. More BRCA1/2 mutation carriers were younger, had cT1 tumors, and had poorly differentiated disease. After matching, 58 BRCA1/2 mutation carriers were similar to 116 non-carriers in terms of age (p = 0.6), cT (p = 0.9), cN stage (p = 0.7), and tumor differentiation (p > 0.9). Among the mutation carriers, the pCR rate was 15.5% for BRCA1/2, 38% (8/21) for BRCA1, and 2.7% (1/37) for BRCA2 versus 7.8% (9/116) for the non-carriers (p < 0.001). After NAC, 5 (41.7%) of the 12 BRCA1 mutation carriers converted to pN0 versus 10 (37%) of the 27 BRCA2 mutation carriers and 19 (20.9%) of the 91 non-carriers (p = 0.3). In the multivariable analysis, BRCA1 mutation status was associated with higher odds of pCR than non-carrier status (odds ratio [OR] 6.31; 95% confidence interval [CI] 1.95-20.5; p = 0.002), whereas BRCA2 mutation status was not (OR 0.45; 95% CI 0.02-2.67; p = 0.5). CONCLUSIONS: This study showed that BRCA1 mutation carriers with HR+/HER2- breast cancers have a higher rate of pCR than sporadic cancers and may derive greater benefit from chemotherapy. The use of NAC to downstage these patients should be considered.

Satisfaction and Well-Being After Contralateral Prophylactic Mastectomy Among BRCA Mutation Carriers and Noncarriers: A Longitudinal Analysis of BREAST-Q Domains.

INTRODUCTION: Contralateral prophylactic mastectomy (CPM) is recommended for BRCA mutation carriers; its use in noncarriers relies on patient choice. We characterized differences in satisfaction and well-being after CPM between BRCA carriers and noncarriers. METHODS: BREAST-Q data were obtained before and after CPM with immediate reconstruction performed at a single institution from 2016 to 2022. Associations between BRCA status and satisfaction with breasts, psychosocial well-being, and sexual well-being were assessed, with adjustment for preoperative scores and relevant confounders. RESULTS: In total, 149 BRCA carriers and 842 noncarriers were included. Response rates varied over time (preoperative, 56%; 6 months, 78%; 1 year, 51%; 2 years, 52%; 3 years, 59%). BRCA carriers were younger (p < 0.001), with a higher rate of neoadjuvant chemotherapy (p < 0.001). More noncarriers had HR+/HER2- tumors (p < 0.001) and underwent endocrine therapy (p < 0.001). Baseline satisfaction with breasts was higher among BRCA carriers (median [interquartile range] score, 70 [53-82] vs. 58 [48-70]; p = 0.006); psychosocial (p = 0.20) and sexual (p = 0.14) well-being were not significantly different between groups. BRCA carriers had a greater decrease in satisfaction with breasts (p = 0.04) and psychological well-being (p = 0.05) from baseline to 6 months; decrease in sexual well-being (p = 0.38) was not significantly different between groups. On univariate and multivariable analyses, BRCA status was not associated with satisfaction with breasts, sexual well-being, or psychosocial well-being. CONCLUSIONS: Satisfaction and well-being were similar between BRCA carriers and noncarriers treated with CPM. Relative to noncarriers, BRCA carriers experienced a greater decline in satisfaction with breasts and psychological well-being at 6 months after CPM.

Long-Term Patient-Reported Outcomes Comparing Oncoplastic Breast Surgery and Conventional Breast-Conserving Surgery: A Propensity Score-Matched Analysis.

INTRODUCTION: Oncoplastic breast surgery (OBS) combines plastic surgery techniques with conventional breast-conserving surgery (BCS) and expands BCS eligibility. Limited data are available on patient-reported outcomes (PROs) after OBS. Here we compare long-term PROs after OBS and BCS utilizing the BREAST-Q. PATIENTS AND METHODS: Women undergoing OBS or BCS between 2006 and 2019 who completed ≥ 1 long-term BREAST-Q survey 3-5 years postoperatively were identified. Baseline characteristics were compared between women who underwent OBS/BCS. Women who underwent OBS were paired with those who underwent BCS using 1:2 propensity matching [by age, body mass index (BMI), race, T stage, and multifocality]. BREAST-Q scores were compared preoperatively and 3-5 years postoperatively. RESULTS: A total of 297 patients were included for analysis (99 OBS/198 BCS). Women who underwent OBS were younger (p < 0.001) and had higher BMI (p = 0.005) and multifocal disease incidence (p = 0.004). There was no difference between groups in nodal stage, re-excision rates, axillary surgery, chemotherapy, endocrine therapy, or radiotherapy. After propensity matching preoperatively, women who underwent OBS reported lower psychosocial well-being (63 versus 100, p = 0.039) but similar breast satisfaction and sexual well-being compared with women who underwent BCS; however, only three patients who underwent BCS had preoperative BREAST-Q scores available for review. In long-term follow-up, women who underwent OBS reported lower psychosocial scores (74 versus 93, p = 0.011) 4 years postoperatively, but not at 5 years (76 versus 77, p = 0.83). There was no difference in long-term breast satisfaction or sexual well-being. CONCLUSIONS: Women who undergo OBS present with a larger disease burden and may represent a group of non-traditional BCS candidates; they reported similar long-term breast satisfaction and sexual well-being compared with women who undergo BCS. While women who underwent OBS reported lower psychosocial well-being scores preoperatively and during a portion of the follow-up period, this difference was no longer seen at 5 years postoperatively.

Does Non-Classic Lobular Carcinoma In Situ at the Lumpectomy Margin Increase Local Recurrence?

BACKGROUND: The clinical significance of nonclassic, lobular carcinoma in situ (NC-LCIS) at the surgical margin of excisions for invasive cancer is unknown. We sought to determine whether NC-LCIS at or near the margin in the setting of a concurrent invasive carcinoma is associated with risk of ipsilateral breast tumor recurrence (IBTR) and locoregional recurrence (LRR). METHODS: Patients with stage 0-III breast cancer and NC-LCIS who underwent lumpectomy between January 2010 and January 2022 at a single institution were retrospectively identified. NC-LCIS margins were stratified as <2 mm, ≥2 mm, or within shave margin. Rates of IBTR and LRR were examined. RESULTS: A total of 511 female patients (median age 60 years [interquartile range (IQR) 52-69]) with NC-LCIS and an associated ipsilateral breast cancer with a median follow-up of 3.4 years (IQR 2.0-5.9) were identified. Final margins for NC-LCIS were ≥2 mm in 348 patients (68%), <2 mm in 37 (7.2%), and within shave margin in 126 (24.6%). Crude incidence of IBTR was 3.3% (n = 17) and that of LRR was 4.9% (n = 25). There was no difference in the crude rate of IBTR by NC-LCIS margin status (IBTR rate: 3.7% ≥2 mm, 0% <2 mm, 3.2% within shave margin, p = 0.8) nor in LRR (LRR rate: 4.9% ≥2 mm, 2.7% <2 mm, 5.6% within shave margin, p = 0.9). CONCLUSIONS: For completely excised invasive breast cancers associated with NC-LCIS, extent of margin width for NC-LCIS was not associated with a difference in IBTR or LRR. These data suggest that the decision to perform reexcision of margin after lumpectomy should be driven by the invasive cancer, rather than the NC-LCIS margin.

Association of Moderate-Risk Breast Cancer Genes with Contralateral Prophylactic Mastectomy and Bilateral Disease.

BACKGROUND: The impact of ATM, CHEK2, and PALB2, the three most prevalent moderate-risk breast cancer genes, on surgical decision making is not well known. METHODS: Our retrospective study included patients with resectable non-metastatic breast cancer who underwent multigene panel testing between July 2014 and January 2020 with at least one genetic alteration (pathogenic or variant of uncertain significance [VUS] in ATM [n = 49], CHEK [n = 57], or PALB2 [n = 27]). Our objectives were to determine the rate of contralateral prophylactic mastectomy (CPM) and the rate of bilateral breast cancer. Univariable analyses (UVA) and multivariable analyses (MVA) were performed to identify factors associated with CPM and bilateral breast cancer. RESULTS: The rate of CPM was 39% (n = 49/127), with 54% (n = 25/46) of patients with a pathogenic mutation and 30% (n = 24/81) of patients with a VUS choosing CPM. On MVA, premenopausal status (odds ratio [OR] 3.46) and a pathogenic alteration (OR 3.01) were associated with increased use of CPM. Bilateral disease was noted in 16% (n = 22/138). Patients with pathogenic mutations had a 22% (n = 11/51) incidence of bilateral breast cancer, while patients with VUS had a 13% (n = 11/87) incidence, although this was not statistically significant on UVA or MVA. On MVA, premenopausal status was associated with a decreased risk of bilateral disease (OR 0.33, p = 0.022). During follow-up, a breast cancer event occurred in 16% (n = 22/138). CONCLUSIONS: Our study identified a high rate of CPM among those with ATM, CHEK2, and PALB2 alterations, including VUS. Further studies are needed to clarify reasons for CPM among patients with moderate-risk alterations.

Patient-Reported Outcome Measures for Patients Who Have Clinical T4 Breast Cancer Treated via Mastectomy with and Without Reconstruction.

BACKGROUND: Patients with clinical T4M0 breast cancer are recommended to undergo neoadjuvant chemotherapy, modified radical mastectomy, and postmastectomy radiotherapy. This study determined whether BREAST-Q scores differ by decision to pursue reconstruction or timing of reconstruction. METHODS: This retrospective, single-institutional study analyzed cT4 breast cancer patients from 2014 to 2021 without evidence of distant metastatic disease undergoing mastectomy with or without reconstruction. As routine care, BREAST-Q was administered preoperatively, then 6 months, 1 year, and 2 years postoperatively. Satisfaction and quality-of-life domains were compared between mastectomy with no reconstruction (NR), immediate reconstruction (IR), and delayed reconstruction (DR) groups. RESULTS: Of the 144 patients eligible for this study, 71 (49%) had NR, 36 (25%) had DR, and 37 (26%) had IR. The patients undergoing reconstruction were younger and more likely to elect contralateral prophylactic mastectomy. Timing of reconstruction was not associated with significant differences in satisfaction with breasts (SATBR) at any time point. For the patients who had DR, breast satisfaction increased over time after reconstructive surgery. Physical well-being of the chest (PWB-CHEST) did not significantly differ among IR, DR, and NR at any time point. The patients who underwent DR experienced improvement in PWB-CHEST scores from preoperative scores. The patients with IR and NR experienced PWB-CHEST decline over time. Psychosocial well-being (PSWB) did not differ significantly across time or by subgroup. CONCLUSIONS: The patients with T4 breast cancer who elected reconstruction did not differ in patient-reported outcomes based on timing of reconstruction. In the DR cohort, SATBR significantly improved after reconstructive surgery. These data can help inform breast reconstructive decision-making for patients facing the choice among DR, IR, and NR.

ASO Visual Abstract: Patient-Reported Outcome Measures in Patients with Clinical T4 Breast Cancer Treated with Mastectomy With and Without Reconstruction.

AIM: Do patient-reported outcome measures differ among clinical T4 patients undergoing mastectomy with and without reconstruction? FINDINGS: Neither reconstruction nor timing of reconstruction were associated with superior outcomes for breast satisfaction, physical well-being of the chest, or psychosocial well-being at any timepoint.