Trends in HR+ metastatic breast cancer survival before and after CDK4/6 inhibitor introduction in the United States: a SEER registry analysis of patients with HER2− and HER2+ metastatic breast cancer

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have improved patient survival in hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2−) metastatic breast cancer (mBC) in clinical trials and real-world studies. However, investigations of survival gains in broader HR+/HER2− mBC populations using epidemiological approaches are limited.

This retrospective study used SEER registry data to assess breast cancer-specific survival (BCSS) in patients diagnosed with HR+/HER2− de novo mBC from 2010 to 2019. Kaplan–Meier and Cox proportional hazards models were used to compare BCSS in patients diagnosed before (2010‒2013 with follow-up to 2014) and after (2015‒2018 with follow-up to 2019) the 2015 guideline recommendations for CDK4/6i use. A comparison was made to patients with HR+/HER2-positive (HER2+) de novo mBC, for which no major guideline changes occurred during 2015–2018.

Data from 11,467 women with HR+/HER2− mBC and 3260 women with HR+/HER2+ mBC were included. After baseline characteristic adjustment, patients with HR+/HER2− mBC diagnosed post-2015 (n = 6163), had an approximately 10% reduction in risk of BC-specific death compared with patients diagnosed pre-2015 (n = 5304; HR = 0.895, p < 0.0001). Conversely, no significant change was observed in HR+/HER2+ BCSS post-2015 (n = 1798) versus pre-2015 (n = 1462). Similar results were found in patients aged ≥ 65 years.

Using one of the largest US population-based longitudinal cancer databases, significant improvements in BCSS were noted in patients with HR+/HER2− mBC post-2015 versus pre-2015, potentially due to the introduction of CDK4/6i post-2015. No significant improvement in BCSS was observed in patients with HR+/HER2+ mBC post-2015 versus pre-2015, likely due to the availability of HER2-directed therapies in both time periods.