Faculty Bibliography

PURPOSE/OBJECTIVE: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/CONCLUSIONS: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.

PURPOSE/OBJECTIVE: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/CONCLUSIONS: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.

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/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.

IMPORTANCE:Rates of lumpectomy for breast cancer management in the United States previously declined in favor of more aggressive surgical options, such as mastectomy and contralateral prophylactic mastectomy (CPM). OBJECTIVE:To evaluate longitudinal trends in the rates of lumpectomy and mastectomy, including unilateral mastectomy vs CPM rates, and to determine characteristics associated with current surgical practice using 3 national data sets. DESIGN AND SETTING:Data from the National Surgical Quality Improvement Program (NSQIP), Surveillance, Epidemiology, and End Results (SEER) program, and National Cancer Database (NCDB) were examined to evaluate trends in lumpectomy and mastectomy rates from 2005 through 2017. Mastectomy rates were also evaluated with a focus on CPM. Longitudinal trends were analyzed using the Cochran-Armitage test for trend. Multivariate logistic regression models were performed on the NCDB data set to identify predictors of lumpectomy and CPM. RESULTS:A study sample of 3 467 645 female surgical breast cancer patients was analyzed. Lumpectomy rates reached a nadir between 2010 and 2013, with a significant increase thereafter. Conversely, in comparison with lumpectomy rates, overall mastectomy rates declined significantly starting in 2013. Cochran-Armitage trend tests demonstrated an annual decrease in lumpectomy rates of 1.31% (95% CI, 1.30%-1.32%), 0.07% (95% CI, 0.01%-0.12%), and 0.15% (95% CI, 0.15%-0.16%) for NSQIP, SEER, and NCDB, respectively, from 2005 to 2013 (P < .001, P = .01, and P < .001, respectively). From 2013 to 2017, the annual increase in lumpectomy rates was 0.96% (95% CI, 0.95%-0.98%), 1.60% (95% CI, 1.59%-1.62%), and 1.66% (95% CI, 1.65%-1.67%) for NSQIP, SEER, and NCDB, respectively (all P < .001). Comparisons of specific mastectomy types showed that unilateral mastectomy and CPM rates stabilized after 2013, with unilateral mastectomy rates remaining higher than CPM rates throughout the entire time period. CONCLUSIONS:This observational longitudinal analysis indicated a trend reversal with an increase in lumpectomy rates since 2013 and an associated decline in mastectomies. The steady increase in CPM rates from 2005 to 2013 has since stabilized. The reasons for the recent reversal in trends are likely multifactorial. Further qualitative and quantitative research is required to understand the factors driving these recent practice changes and their associations with patient-reported outcomes.

BACKGROUND:National Comprehensive Center Network guidelines recommend radiotherapy (RT) omission in women age ≥ 70 years with estrogen receptor-positive (ER+), cN0, T1 tumors post-lumpectomy if they receive endocrine therapy (ET). However, little is known about the impact of poor adherence on locoregional recurrence (LRR) in elderly women forgoing RT. METHODS:Women age ≥ 70 years with pT1-2 ER+ breast cancer undergoing lumpectomy without RT from 2004 to 2019 were identified from a prospectively maintained database. ET adherence, calculated as treatment duration over follow-up time up to 5 years, was determined by chart review. We compared clinicopathologic characteristics and rates of LRR between women with high adherence (≥ 80%), low adherence (< 80%), and no ET. RESULTS:Of 968 women (27 bilateral cancers), adherence was high in 676 (70%) and low in 162 (17%); 130 (13%) took no ET. Younger age and use of aromatase inhibitor were associated with high adherence. On multivariable analysis, tumor size (hazard ratio [HR] 1.67, 95% confidence interval [CI] 1.03-2.68, p = 0.04) and high adherence (HR 0.13, 95% CI 0.07-0.26, p < 0.001) were significantly associated with LRR. At 53 months median follow-up, the 5-year rate of LRR was 3.1% (95% CI 2.4-3.9%) with high adherence, 14.7% (95% CI 11.7-17.7%) with low adherence, and 17.9% (95% CI 13.9-21.8%) with no ET (p < 0.01). CONCLUSIONS:Although adherence to ET was high overall, in the 30% of women with low adherence or no ET, LRR rates were significantly increased. Counseling regarding the distinct toxicities of ET and RT can help patients choose the therapy to which they will likely adhere to.

BACKGROUND:Younger women (age ≤ 40 years) with breast cancer undergoing neoadjuvant chemotherapy (NAC) have higher rates of pathologic complete response (pCR); however, it is unknown whether axillary or breast downstaging rates differ by age. In this study, we compared pCR incidence and surgical downstaging rates of the breast and axilla post NAC, between patients aged ≤ 40, 41-60, and ≥ 61 years. METHODS:We identified 1383 women with stage I-III breast cancer treated with NAC and subsequent surgery from November 2013 to December 2018. pCR and breast/axillary downstaging rates were assessed and compared across age groups. RESULTS:Younger women were significantly more likely to have ductal histology, poorly differentiated tumors, and BRCA mutations; 35% of tumors were hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-), 36% were HER2-positive (HER2+), and 29% were triple negative (TN), with similar subtype distribution across age groups (p = 0.6). Overall, pCR rates did not differ by age, however among patients with TN tumors (n = 394), younger women had higher pCR rates (52% vs. 35% among those aged 41-60 years and 29% among those aged ≥61 years; p = 0.007) and were more likely to have tumors with high tumor-infiltrating lymphocyte (TIL) concentrations (p < 0.001). Downstaging to breast-conserving surgery (BCS) eligibility post NAC among initially BCS-ineligible patients was similar across age groups; younger women chose BCS less often (p < 0.001). Among cN1 patients (n = 813), 52% of women ≤40 years of age avoided axillary lymph node dissection (ALND) with NAC, versus 39% and 37% in the older groups (p < 0.001). CONCLUSIONS:Younger women undergoing NAC for axillary downstaging were more likely to avoid ALND across all subtypes; however, overall pCR rates did not differ by age. Despite equivalent breast downstaging and BCS eligibility rates across age groups, younger women were less likely to undergo BCS.

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/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.