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.

Pathologic complete response after neoadjuvant systemic therapy for breast cancer in BRCA mutation carriers and noncarriers.

BRCA1 and BRCA2 pathogenic variant carriers develop breast cancers with distinct pathological characteristics and mutational signatures that may result in differential response to chemotherapy. We compared rates of pathologic complete response (pCR) after NAC between BRCA1/2 variant carriers and noncarriers in a cohort of 1426 women (92 [6.5%] BRCA1 and 73 [5.1%] BRCA2) with clinical stage I-III breast cancer treated with NAC followed by surgery from 11/2013 to 01/2022 at Memorial Sloan Kettering Cancer Center. The majority received doxorubicin/cyclophosphamide/paclitaxel therapy (93%); BRCA1/2 carriers were more likely to receive carboplatin (p < 0.001). Overall, pCR was achieved in 42% of BRCA1 carriers, 21% of BRCA2 carriers, and 26% of noncarriers (p = 0.001). Among clinically node-positive (cN+) patients, nodal pCR was more frequent in BRCA1/2 carriers compared to noncarriers (53/96 [55%] vs. 371/856 [43%], p = 0.015). This difference was seen in HR+/HER2- (36% vs. 20% of noncarriers; p = 0.027) and TN subtypes (79% vs. 45% of noncarriers; p < 0.001). In a multivariable analysis of the overall cohort, BRCA1 status, and TN and HER2+ subtypes were independently associated with pCR. These data indicate that BRCA1 carriers may be more likely to achieve overall and nodal pCR in response to NAC compared with BRCA2 carriers and patients with sporadic disease. Further studies with a larger cohort of BRCA1/2 mutation carriers are needed, as a small sample size may have a restricted ability to detect a significant association between mutational status and pCR in sensitivity analyses stratified by subtype and adjusted for clinically relevant factors.

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.

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.

Omission of Axillary Dissection Following Nodal Downstaging With Neoadjuvant Chemotherapy.

Importance: Data on oncological outcomes after omission of axillary lymph node dissection (ALND) in patients with breast cancer that downstages from node positive to negative with neoadjuvant chemotherapy are sparse. Additionally, the best axillary surgical staging technique in this scenario is unknown. Objective: To investigate oncological outcomes after sentinel lymph node biopsy (SLNB) with dual-tracer mapping or targeted axillary dissection (TAD), which combines SLNB with localization and retrieval of the clipped lymph node. Design, Setting, and Participants: In this multicenter retrospective cohort study that was conducted at 25 centers in 11 countries, 1144 patients with consecutive stage II to III biopsy-proven node-positive breast cancer were included between April 2013 and December 2020. The cumulative incidence rates of axillary, locoregional, and any invasive (locoregional or distant) recurrence were determined by competing risk analysis. Exposure: Omission of ALND after SLNB or TAD. Main Outcomes and Measures: The primary end points were the 3-year and 5-year rates of any axillary recurrence. Secondary end points included locoregional recurrence, any invasive (locoregional and distant) recurrence, and the number of lymph nodes removed. Results: A total of 1144 patients (median [IQR] age, 50 [41-59] years; 78 [6.8%] Asian, 105 [9.2%] Black, 102 [8.9%] Hispanic, and 816 [71.0%] White individuals; 666 SLNB [58.2%] and 478 TAD [41.8%]) were included. A total of 1060 patients (93%) had N1 disease, 619 (54%) had ERBB2 (formerly HER2)-positive illness, and 758 (66%) had a breast pathologic complete response. TAD patients were more likely to receive nodal radiation therapy (85% vs 78%; P = .01). The clipped node was successfully retrieved in 97% of TAD cases and 86% of SLNB cases (without localization). The mean (SD) number of sentinel lymph nodes retrieved was 3 (2) vs 4 (2) (P < .001), and the mean (SD) number of total lymph nodes removed was 3.95 (1.97) vs 4.44 (2.04) (P < .001) in the TAD and SLNB groups, respectively. The 5-year rates of any axillary, locoregional, and any invasive recurrence in the entire cohort were 1.0% (95% CI, 0.49%-2.0%), 2.7% (95% CI, 1.6%-4.1%), and 10% (95% CI, 8.3%-13%), respectively. The 3-year cumulative incidence of axillary recurrence did not differ between TAD and SLNB (0.5% vs 0.8%; P = .55). Conclusions and Relevance: The results of this cohort study showed that axillary recurrence was rare in this setting and was not significantly lower after TAD vs SLNB. These results support omission of ALND in this population.

Quality of Life After Axillary Lymph Node Dissection Among Racial and Ethnic Minority Women.

Importance: Higher lymphedema rates after axillary lymph node dissection (ALND) have been found in Black and Hispanic women; however, there is poor correlation between subjective symptoms, quality of life (QOL), and measured lymphedema. Additionally, racial and ethnic differences in QOL have been understudied. Objective: To evaluate the association of race and ethnicity with long-term QOL in patients with breast cancer treated with ALND. Design, Setting, and Participants: This cohort study enrolled women aged 18 years and older with breast cancer who underwent unilateral ALND at a tertiary cancer center between November 2016 and March 2020. Preoperatively and at 6-month intervals, arm volume was measured by perometer and QOL was assessed using the Upper Limb Lymphedema-27 (ULL-27) questionnaire, a validated tool for assessing lymphedema that evaluates how arm symptoms affect physical, psychological, and social functioning. Data were analyzed from November 2016 to October 2023. Exposures: Breast surgery and unilateral ALND in the primary setting or after sentinel lymph node biopsy. Main Outcomes and Measures: Scores in each domain of the ULL-27 were compared by race and ethnicity. Factors impacting QOL were identified using multivariable regression analyses. Results: The study included 281 women (median [IQR] age, 48 [41-58] years) with breast cancer who underwent unilateral ALND and had at least 6 months of follow-up. Of these, 30 patients (11%) self-identified as Asian individuals, 57 (20%) as Black individuals, 23 (8%) as Hispanic individuals, and 162 (58%) as White individuals; 9 individuals (3%) who did not identify as part of a particular group or who were missing race and ethnicity data were categorized as having unknown race and ethnicity. Median (IQR) follow-up was 2.97 (1.96-3.67) years. The overall 2-year lymphedema rate was 20% and was higher among Black (31%) and Hispanic (27%) women compared with Asian (15%) and White (17%) women (P = .04). Subjective arm swelling was more common among Asian (57%), Black (70%), and Hispanic (87%) women than White (44%) women (P < .001), and lower physical QOL scores were reported by racial and ethnic minority women at nearly every follow-up. For example, at 24 months, median QOL scores were 87, 79, and 80 for Asian, Black, and Hispanic women compared with 92 for White women (P = .003). On multivariable analysis, Asian race (ß = -5.7; 95% CI, -9.5 to -1.8), Hispanic ethnicity (ß = -10.0; 95% CI, -15.0 to -5.2), and having Medicaid (ß = -5.4; 95% CI, -9.2 to -1.7) or Medicare insurance (ß = -6.9; 95% CI, -10.0 to -3.4) were independently associated with worse physical QOL (all P < .001). Conclusions and Relevance: Findings of this cohort study suggest that Asian, Black, and Hispanic women experience more subjective arm swelling after unilateral ALND for breast cancer compared with White women. Black and Hispanic women had higher rates of objective lymphedema than their White counterparts. Both minority status and public medical insurance were associated with worse physical QOL. Understanding disparities in QOL after ALND is an unmet need and may enable targeted interventions to improve QOL for these patients.

Artificial Intelligence Decision Support for Triple-Negative Breast Cancers on Ultrasound.

OBJECTIVE: To assess performance of an artificial intelligence (AI) decision support software in assessing and recommending biopsy of triple-negative breast cancers (TNBCs) on US. METHODS: Retrospective institutional review board-approved review identified patients diagnosed with TNBC after US-guided biopsy between 2009 and 2019. Artificial intelligence output for TNBCs on diagnostic US included lesion features (shape, orientation) and likelihood of malignancy category (benign, probably benign, suspicious, and probably malignant). Artificial intelligence true positive was defined as suspicious or probably malignant and AI false negative (FN) as benign or probably benign. Artificial intelligence and radiologist lesion feature agreement, AI and radiologist sensitivity and FN rate (FNR), and features associated with AI FNs were determined using Wilcoxon rank-sum test, Fisher's exact test, chi-square test of independence, and kappa statistics. RESULTS: The study included 332 patients with 345 TNBCs. Artificial intelligence and radiologists demonstrated moderate agreement for lesion shape and orientation (k = 0.48 and k = 0.47, each P <.001). On the set of examinations using 6 earlier diagnostic US, radiologists recommended biopsy of 339/345 lesions (sensitivity 98.3%, FNR 1.7%), and AI recommended biopsy of 333/345 lesions (sensitivity 96.5%, FNR 3.5%), including 6/6 radiologist FNs. On the set of examinations using immediate prebiopsy diagnostic US, AI recommended biopsy of 331/345 lesions (sensitivity 95.9%, FNR 4.1%). Artificial intelligence FNs were more frequently oval (q < 0.001), parallel (q < 0.001), circumscribed (q = 0.04), and complex cystic and solid (q = 0.006). CONCLUSION: Artificial intelligence accurately recommended biopsies for 96% to 97% of TNBCs on US and may assist radiologists in classifying these lesions, which often demonstrate benign sonographic features.

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.

Contrast-Enhanced Mammography for Women with Palpable Breast Abnormalities.

RATIONALE AND OBJECTIVES: To examine the role of contrast-enhanced mammography (CEM) in the work-up of palpable breast abnormalities. MATERIALS AND METHODS: In this single-center combination prospective-retrospective study, women with palpable breast abnormalities underwent CEM evaluation prospectively, comprising the acquisition of low energy (LE) images and recombined images (RI) which depict enhancement, followed by targeted ultrasound (US). Two independent readers retrospectively reviewed the imaging and assigned BI-RADS assessment based on LE alone, LE plus US, RI with LE plus US (CEM plus US), and RI alone. Pathology results or 1-year follow-up imaging served as the reference standard. RESULTS: 237 women with 262 palpable abnormalities were included (mean age, 51 years). Of the 262 palpable abnormalities, 116/262 (44%) had no imaging correlate and 242/262 (92%) were benign. RI alone had better specificity compared to LE plus US (Reader 1, 94% versus 89% (p = 0.009); Reader 2, 93% versus 88% (p = 0.03)), better positive predictive value (Reader 1, 52% versus 42% (p = 0.04); Reader 2, 53% versus 42% (p = 0.04)), and better accuracy (Reader 1, 93% versus 89% (p = 0.05); Reader 2, 93% versus 90% (p = 0.06)). CEM plus US was not significantly different in performance metrics versus LE plus US. CONCLUSION: RI had better specificity compared to LE in combination with US. There was no difference in performance between CEM plus US and LE plus US, likely reflecting the weight US carries in radiologist decision-making. However, the results indicate that the absence of enhancement on RI in the setting of palpable lesions may help avoid benign biopsies.

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.

Comparison of Axillary Lymph Nodes on Breast MRI Before and After COVID-19 Booster Vaccination.

RATIONALE AND OBJECTIVES: Vaccine-related lymphadenopathy is a frequent finding following initial coronavirus disease 2019 (COVID-19) vaccination, but the frequency after COVID-19 booster vaccination is still unknown. In this study we compare axillary lymph node morphology on breast MRI before and after COVID-19 booster vaccination. MATERIALS AND METHODS: This retrospective, single-center, IRB-approved study included patients who underwent breast MRI between October 2021 and December 2021 after the COVID-19 booster vaccination. The axillary lymph node with the greatest cortical thickness ipsilateral to the side of vaccination was measured on MRI after booster vaccination and before initial COVID-19 vaccination. Comparisons were made between patients with and without increase in cortical thickness of ≥ 0.2 cm. Continuous covariates were compared using Wilcoxon rank-sum test and categorical covariates were compared using Fisher's exact test. Multiple comparison adjustment was made using the Benjamini-Hochberg procedure. RESULTS: All 128 patients were included. Twenty-four of 128 (19%) displayed an increase in lymph node cortical thickness of ≥ 0.2 cm. Patients who received the booster more recently were more likely to present cortical thickening, with a median of 9 days (IQR 5, 20) vs. 36 days (IQR 18, 59) (p < 0.001). Age (p = 0.5) and type of vaccine (p = 0.7) were not associated with thickening. No ipsilateral breast cancer or malignant lymphadenopathy were diagnosed on follow-up. CONCLUSION: Axillary lymphadenopathy on breast MRI following COVID-19 booster vaccination is a frequent finding, especially in the first 3 weeks after vaccination. Additional evaluation or follow-up may be omitted in patients with low concern for malignancy.

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.

Factors Affecting Antidepressant Response Trajectories: A Veterans Affairs Augmentation and Switching Treatments for Improving Depression Outcomes Trial Report.

Background: In this secondary analysis of the VA Augmentation and Switching Treatments for Improving Depression Outcomes (VAST-D) study we used antidepressant response trajectories to assess the association of treatment and multiple clinical/demographic factors with the probability of response. Methods: Using data from VAST-D, a multi-site, randomized, single-blind trial with parallel-assignment to one of three treatment interventions in 1522 Veterans whose major depressive disorder was unresponsive to at least one antidepressant trial, we evaluated response patterns using group-based trajectory modeling (GBTM). A weighted multinomial logistic regression analysis with backward elimination and additional exploratory analyses were performed to evaluate the association of multiple clinical/demographic factors with the probability of inclusion into specific trajectories. Additional exploratory analyses were used to identify factors associated with trajectory group membership that could have been missed in the primary analysis. Results: GBTM showed the best fit for depression symptom change was comprised of six trajectories, with some trajectories demonstrating minimal improvement and others showing a high probability of remission. High baseline depression and anxiety severity scores decreased, and early improvement increased, the likelihood of inclusion into the most responsive trajectory in both the GBTM and exploratory analyses. Conclusion: While multiple factors influence responsiveness, the probability of inclusion into a specific depression symptom trajectory is most strongly influenced by three factors: baseline depression, baseline anxiety, and the presence of early improvement.

A Review of the Estimation of Sensitivity and Specificity in the Context of Time-Dependent Outcomes.

Time is an essential element in the field of survival analysis. Time to an event is essential in adjudicating diagnostic utility and determining the effectiveness of treatment. However, time-to-event outcomes-in a sense-are complicated to deal with, since they involve both a binary component, which is the outcome itself (death or recurrence) and a continuous component, which is the time for the occurrence of the outcome. In such scenarios, simpler metrics such as sensitivity, specificity, positive predictive value, negative predictive value, and area under the curve are insufficient to establish the utility of a diagnostic marker. Given the above constraint, this review discusses established ways in which sensitivity and specificity can be determined and are therefore sufficient in establishing utility in the context of time-dependent outcomes. This review also discusses how studies investigating the sensitivity and specificity of a diagnostic marker in the context of time-dependent outcomes can be improved through the use of existing user-friendly statistical software. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 3.

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.