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.

Insufficient Reporting of Race and Ethnicity in Breast Cancer Clinical Trials.

BACKGROUND: Reporting race and ethnicity in clinical trial publications is critical for determining the generalizability and effectiveness of new treatments. This is particularly important for breast cancer, in which Black women have been shown to have between 40 and 100% higher mortality rate yet are underrepresented in trials. Our objective was to describe changes over time in the reporting of race/ethnicity in breast trial publications. PATIENTS AND METHODS: We searched ClinicalTrials.gov to identify the primary publication linked to trials with results posted from May 2010-2022. Statistical analysis included summed frequencies and a linear regression model of the proportion of articles reporting race/ethnicity and the proportion of non-White enrollees over time. RESULTS: A proportion of 72 of the 98 (73.4%) studies that met inclusion criteria reported race/ethnicity. In a linear regression model of the proportion of studies reporting race/ethnicity as a function of time, there was no statistically significant change, although we detected a signal toward a decreasing trend (coefficient for quarter = -2.2, p = 0.2). Among all studies reporting race and ethnicity over the study period, the overall percentage of non-White enrollees during the study period was 21.9%, [standard error (s.e.) 1.8, 95% confidence interval (CI) 18.4, 25.5] with a signal towards a decreasing trend in Non-White enrollment [coefficient for year-quarter = -0.8 (p = 0.2)]. CONCLUSION: Our data demonstrate that both race reporting and overall representation of minority groups in breast cancer clinical trials did not improve over the last 12 years and may have, in fact, decreased. Increased reporting of race and ethnicity data forces the medical community to confront disparities in access to clinical trials. This may improve efforts to recruit and retain members of minority groups in clinical trials, and over time, reduce racial disparities in oncologic outcomes.

Changes in Surgical Management of the Axilla Over 11 Years - Report on More Than 1500 Breast Cancer Patients Treated with Neoadjuvant Chemotherapy on the Prospective I-SPY2 Trial.

BACKGROUND: Axillary surgery after neoadjuvant chemotherapy (NAC) is becoming less extensive. We evaluated the evolution of axillary surgery after NAC on the multi-institutional I-SPY2 prospective trial. METHODS: We examined annual rates of sentinel lymph node (SLN) surgery with resection of clipped node, if present), axillary lymph node dissection (ALND), and SLN and ALND in patients enrolled in I-SPY2 from January 1, 2011 to December 31, 2021 by clinical N status at diagnosis and pathologic N status at surgery. Cochran-Armitage trend tests were calculated to evaluate patterns over time. RESULTS: Of 1578 patients, 973 patients (61.7%) had SLN-only, 136 (8.6%) had SLN and ALND, and 469 (29.7%) had ALND-only. In the cN0 group, ALND-only decreased from 20% in 2011 to 6.25% in 2021 (p = 0.0078) and SLN-only increased from 70.0% to 87.5% (p = 0.0020). This was even more striking in patients with clinically node-positive (cN+) disease at diagnosis, where ALND-only decreased from 70.7% to 29.4% (p < 0.0001) and SLN-only significantly increased from 14.6% to 56.5% (p < 0.0001). This change was significant across subtypes (HR-/HER2-, HR+/HER2-, and HER2+). Among pathologically node-positive (pN+) patients after NAC (n = 525) ALND-only decreased from 69.0% to 39.2% (p < 0.0001) and SLN-only increased from 6.9% to 39.2% (p < 0.0001). CONCLUSIONS: Use of ALND after NAC has significantly decreased over the past decade. This is most pronounced in cN+ disease at diagnosis with an increase in the use of SLN surgery after NAC. Additionally, in pN+ disease after NAC, there has been a decrease in use of completion ALND, a practice pattern change that precedes results from clinical trials.

Breast Conservation Surgery and Mastectomy Have Similar Locoregional Recurrence After Neoadjuvant Chemotherapy: Results From 1462 Patients on the Prospective, Randomized I-SPY2 Trial.

Neoadjuvant chemotherapy (NAC) increases rates of successful breast-conserving surgery (BCS) in patients with breast cancer. However, some studies suggest that BCS after NAC may confer an increased risk of locoregional recurrence (LRR). We assessed LRR rates and locoregional recurrence-free survival (LRFS) in patients enrolled on I-SPY2 (NCT01042379), a prospective NAC trial for patients with clinical stage II to III, molecularly high-risk breast cancer. Cox proportional hazards models were used to evaluate associations between surgical procedure (BCS vs mastectomy) and LRFS adjusted for age, tumor receptor subtype, clinical T category, clinical nodal status, and residual cancer burden (RCB). In 1462 patients, surgical procedure was not associated with LRR or LRFS on either univariate or multivariate analysis. The unadjusted incidence of LRR was 5.4% after BCS and 7.0% after mastectomy, at a median follow-up time of 3.5 years. The strongest predictor of LRR was RCB class, with each increasing RCB class having a significantly higher hazard ratio for LRR compared with RCB 0 on multivariate analysis. Triple-negative receptor subtype was also associated with an increased risk of LRR (hazard ratio: 2.91, 95% CI: 1.8-4.6, P < 0.0001), regardless of the type of operation. In this large multi-institutional prospective trial of patients completing NAC, we found no increased risk of LRR or differences in LRFS after BCS compared with mastectomy. Tumor receptor subtype and extent of residual disease after NAC were significantly associated with recurrence. These data demonstrate that BCS can be an excellent surgical option after NAC for appropriately selected patients.

Disparity in Breast Cancer Care: Current State of Access to Screening, Genetic Testing, Oncofertility, and Reconstruction.

Breast cancer is the most common cancer diagnosed in women, accounting for an estimated 30% of all new cancer diagnoses in women in 2022. Advances in breast cancer treatment have reduced the mortality rate over the past 25 years by up to 34% but not all groups have benefitted equally from these improvements. These disparities span the continuum of care from screening to the receipt of guideline-concordant therapy and survivorship. At the 2022 American College of Surgeons Clinical Congress, a panel session was dedicated to educating and discussing methods of addressing these disparities in a coordinated manner. While there are multilevel solutions to address these disparities, this article focuses on screening, genetic testing, reconstruction, and oncofertility.

Pregnancy-associated breast cancer: does timing of presentation affect outcome?

PURPOSE: Pregnancy-associated breast cancer (PABC) comprises breast cancer diagnosed during the gestational period or within 12 months postpartum. While the incidence of PABC appears to be increasing, data regarding prognosis remain limited. METHODS: Here we evaluate clinicopathologic features, treatments, and clinical outcomes among women with stage 0-III PABC diagnosed between 1992 and 2020. Comparisons were made between women who were diagnosed with PABC during gestation and those who were diagnosed within 12 months postpartum. RESULTS: A total of 341 women were identified, with a median age of 36 years (range 25-46). The pregnancy group comprised 119 (35%) women, while 222 (65%) women made up the postpartum group. Clinicopathologic features were similar between groups, with most patients being parous and presenting with stage I and II disease. Treatment delays were uncommon, with a median time from histologic diagnosis to treatment of 4 weeks for both groups. Recurrence-free survival was similar between groups: 67% at 10 years for both. While 10-year overall survival appeared higher in the postpartum group (83% versus 78%, p = 0.02), only the presence of nodal metastases was associated with an increased risk of death (hazard ratio 5.61, 95% CI 2.20-14.3, p < 0.001), whereas timing of diagnosis and receptor profile did not reach statistical significance. CONCLUSION: Clinicopathologic features of women with PABC are similar regardless of timing of diagnosis. While 10-year recurrence-free survival is similar between groups, 10-year overall survival is higher among women diagnosed postpartum; however, timing of diagnosis may not be the driving factor in determining survival outcomes.

Diversity, Equity, and Inclusion in Clinical Trials.

Minority groups are vastly underrepresented in clinical trial participants and leadership. Because these studies provide innovative and revolutionary treatment options to patients with cancer and have the potential to extend survival, it is imperative that public and private stakeholders, as well as hospital and clinical trial leadership, prioritize equity and inclusion of diverse populations in clinical trial development and recruitment strategies. Achieving equity in clinical trials could be an important step in reducing the overall cancer burden and mortality disparities in vulnerable populations.

The Landmark Series-Addressing Disparities in Breast Cancer Screening: New Recommendations for Black Women.

Randomized, clinical trials have established the efficacy of screening mammography in improving survival from breast cancer for women through detection of early, asymptomatic disease. However, disparities in survival rates between black women and women from other racial and ethnic groups following breast cancer diagnosis persist. Various professional groups have different, somewhat conflicting, guidelines with regards to recommended age for commencing screening as well as recommended frequency of screening exams, but the trials upon which these recommendations are based were not specifically designed to examine benefit among black women. Furthermore, these recommendations do not appear to incorporate the unique epidemiological circumstances of breast cancer among black women, including higher rates of diagnosis before age 40 years and greater likelihood of advanced stage at diagnosis, into their formulation. In this review, we examined the epidemiologic and socioeconomic factors that are associated with breast cancer among black women and assess the implications of these factors for screening in this population. Specifically, we recommend that by no later than age 25 years, all black women should undergo baseline assessment for future risk of breast cancer utilizing a model that incorporates race (e.g., Breast Cancer Risk Assessment Tool [BCRAT], formerly the Gail model) and that this assessment should be conducted by a breast specialist or a healthcare provider (e.g., primary care physician or gynecologist) who is trained to assess breast cancer risk and is aware of the increased risks of early (i.e., premenopausal) and biologically aggressive (e.g., late-stage, triple-negative) breast cancer among black women.

Fertility Preservation in Young Women with Breast Cancer: Impact on Treatment and Outcomes.

BACKGROUND: The impact of chemotherapy timing on the fertility preservation (FP) decision is poorly understood. Here we evaluate factors associated with FP completion among women age ≤ 45 years with breast cancer who received chemotherapy and consulted with a reproductive endocrinology and infertility (REI) specialist, and report pregnancy and oncologic outcomes. PATIENTS AND METHODS: This retrospective review included all women age ≤ 45 years diagnosed with stage I-III unilateral breast cancer at Memorial Sloan Kettering Cancer Center between 2009 and 2015 who received chemotherapy and consulted with an REI specialist. Clinicopathologic features and factors associated with the decision to undergo FP were analyzed, and comparisons were made with the Wilcoxon rank-sum test, Chi-square test, or Fisher's exact test. Survival curves were constructed using the Kaplan-Meier method. RESULTS: Among the 172 women identified, median age was 34 years (interquartile range 31-37 years). The majority of women were single (n = 99, 57.6%) and nulliparous (n = 134, 77.9%). Most women underwent FP (n = 121, 70.3%). Factors associated with the decision to undergo FP included younger median age (33 vs. 37 years, p < 0.001), having private insurance (p < 0.001), nulliparity (p < 0.001), and referral from Breast Surgery (p = 0.004). Tumor characteristics and treatments were similar between women who underwent FP and those who declined. Overall survival and recurrence-free survival were also similar between groups. Women who underwent FP were more likely to have a biological child after breast cancer treatment. CONCLUSIONS: Women underwent FP at high rates independent of timing of chemotherapy and oncologic factors. FP is associated with having a biological child and does not compromise oncologic outcomes.

The Role of Safety-Net Hospitals in Reducing Disparities in Breast Cancer Care.

Advances in breast cancer screening and systemic therapies have been credited with profound improvements in breast cancer outcomes; indeed, 5-year relative survival rate approaches 91% in the USA (U.S. National Institutes of Health NCI. SEER Training Modules, Breast). While breast cancer mortality has been declining, oncologic outcomes have not improved equally among all races and ethnicities. Many factors have been implicated in breast cancer disparities; chief among them is limited access to care which contributes to lower rates of timely screening mammography and, once diagnosed with breast cancer, lower rates of receipt of guideline concordant care (Wu, Lund, Kimmick GG et al. in J Clin Oncol 30(2):142-150, 2012). Hospitals with a safety-net mission, such as the essential hospitals, historically have been dedicated to providing high-quality care to all populations and have eagerly embraced the role of caring for the most vulnerable and working to eliminate health disparities. In this article, we review landmark articles that have evaluated the role safety-net hospitals have played in providing equitable breast cancer care including to those patients who face significant social and economic challenges.

Timing of Presentation and Outcomes of Women with Stage IV Pregnancy-Associated Breast Cancer (PABC).

BACKGROUND: Pregnancy-associated breast cancer (PABC) and concurrent, or early development of, stage IV disease is uncommon. Given this rarity, and complexities surrounding pregnancy, data are limited regarding PABC treatment and outcomes. We evaluated oncologic, obstetric, and fetal outcomes of women with stage IV PABC in relation to presentation timing and treatment. PATIENTS AND METHODS: Our retrospective review of an institutional database identified women with stage IV PABC from 1998 to 2018. PABC was defined as diagnosis during pregnancy or ≤ 1 year postpartum. Clinicopathologic, treatment, and outcome variables were compared between women diagnosed during pregnancy versus postpartum. RESULTS: We identified 77 women (median age 35 years; interquartile range [IQR] 32-37 years): 51 (66%) in the postpartum group and 26 (34%) in the pregnant group, including 9 with therapeutic or spontaneous abortion. Among 17 women who continued pregnancy, no obstetric or fetal complications were noted. Clinicopathologic and treatment variables did not differ between groups. Of 43 women dead from disease, 15 had triple negative (TN) tumors. Median overall survival (OS) of TN tumors was 14 months (range 5-39 months); OS was associated with hormone receptor-positive and human epidermal growth factor receptor 2 (HER2) positive tumors (p < 0.01). At 31 months (range 0-137 months) median follow-up, the 5-year OS was 34% (95% confidence interval 21-46%), and did not differ among pregnant and postpartum groups (p = 0.2). CONCLUSIONS: Women with stage IV TN PABC had high mortality rates despite multimodality therapy. Timing of presentation did not affect management decisions or OS, even for women who completed pregnancy. Further research to understand PABC biology, focusing on TN tumors, is warranted.