E26: Males with Hormone-Receptor Positive Breast Cancer Treated with Endocrine Therapy Have Worse Survival Than Females

A significant majority of male breast tumors are estrogen-receptor positive (ER+)/human epidermal growth factor 2 negative (HER2-), but lack of male participation in clinical trials has led to a scarcity of information on male breast tumor response to endocrine therapy (ET). In this study, we sought to determine the effect of sex on clinical outcomes in patients with ER+/HER2- breast cancer (BC) treated with ET to inform sex-specific differences in response to therapy.

Methods: Using the National Cancer Database, adults 18 years of age and older who were diagnosed with stage 1-4 ER+/HER2- BC between 2004-2018 were included. Predictors of ET receipt in males and predictors of mortality in patients who received ET were modeled using multivariable logistic regression. Overall survival was examined with Kaplan-Meier analysis.

Results:

A total of 1,171,562 patients were included, with 11,059 (0.9%) males. ET was given to 821,926 (70.2%) patients. Males were less likely to receive ET (67.9% vs 70.2%, p< 0.001). After adjusting for comorbidities and facility characteristics, predictors of ET receipt in males included younger age (odds ratio [OR] 0.99, 95% confidence interval [CI95] 0.99-1.00) and having insurance compared to no insurance (OR 1.60, CI95 1.16-2.21). Black compared to White males and grade 3 compared to grade 1 tumors were less likely to receive ET (OR 0.72, CI95 0.63-0.83; OR 0.71, CI95 0.61-0.83). No other clinical characteristics were significant predictors of ET. Males treated with ET had significantly worse survival than females treated with ET (Figure, p< 0.001). Clinical predictors of mortality included higher stage at diagnosis (stage 2 compared to 1, OR 1.91, CI95 1.87-1.94; stage 3, OR 4.95, CI95 4.81-5.10; stage 4, OR 20.7, CI95 20.0-21.4), lobular compared to ductal histology (OR 1.03, CI95 1.01-1.06), and higher grade (2 compared to 1, OR 1.14, 95CI 1.11-1.16; 3 compared to 1, OR 1.80, CI95 1.76-1.84). After adjusting for age, race, place of residence, comorbidities, and stage, male sex was significantly associated with increased odds of death (OR 1.33, CI95 1.24-1.42).

Conclusions:

Males with ER+/HER2- BC treated with ET have worse survival compared to female counterparts. Differences in sex-specific life expectancy, tumor biology, and response to ET may explain this survival difference. Prospective trials are needed to identify underlying causes of worse clinical outcomes and determine the efficacy of ET in men with ER+/HER2- breast cancer.