Differences in Breast Cancer Survival by Molecular Subtypes in the United States

Background: Although incidence rates of breast cancer molecular subtypes are well documented, effects of molecular subtypes on breast cancer-specific survival using the largest population coverage to date are unknown in the U.S. population. Methods: Using Surveillance, Epidemiology and End Results cancer registry data, we assessed survival after breast cancer diagnosis among women diagnosed during 2010 to 2013 and followed through December 31, 2014, Breast cancer molecular subtypes defined by joint hormone receptor [HR, estrogen receptor (ER) and/or progesterone receptor (PR)] and HER2 status were assessed. Multiple imputation was used to fill in missing receptor status. Four-year breast cancer-specific survival per molecular subtypes and clinical/demographic factors were calculated. A Cox proportional hazards model was used to evaluate survival while controlling for clinical and demographic factors. Results: The best survival pattern was observed among women with HR+/HER2(-) subtype (survival rate of 92.5% at 4 years), followed by HR+/HER2(+) (90.3%), HR+/HER2(+) (82.7%), and finally worst survival for triple-negative subtype (77.0%). Notably, failing to impute cases with missing receptor status leads to overestimation of survival because those with missing receptor status tend to have worse prognostic features. Survival differed substantially by stage at diagnosis. Among de nova stage IV disease, women with HR+/HER2(+) subtype experienced better survival than those with HR+/HER2(+\)subtype (45.5% vs. 35.9%), even after controlling for other factors. Conclusions: Divergence of survival curves in stage IV HR+/HER2(+) versus HR+/HER2(+) subtype is likely attributable to major advances in HER2-targeted treatment. Impact: Contrary to conventional thought. HR+/HER2(+) subtype experienced better survival than HR+/HER2(+) in advanced-stage disease.