Prognostic value of hormone receptor expression in HR+/HER2- advanced BC receiving first-line endocrine therapy plus CDK4/6 inhibitors

Endocrine therapy (ET) plus CDK4/6 inhibitors (CDJ4/6iis the recommended first-line treatment for patients with HR-positive, HER2-negative advanced breast cancer (HR+/HER2- aBC). The prognostic value of the spectrum of ERα and PgR expression in this setting is not wel understood. Analysis of results from the multicenter observational Italian PALMARES-2 study evaluated the association between ERα expression and real-world progression-free survival (rwPFS) or time-to-chemotherapy (rwTTC) in patients with HER+/HER2- aBC receiving first-line ET plus CDK4/6i. ERα expression was classified as low-intermediate (LI; 1-49%), high (H; 50%-89%), or very high (VH; 90%-100%). Among 4115 patients with availabe ERα assessment. 157 (3.8%) had ER-LI, 967 (23.5%) had ER-H, and 2991 (72.7%) had ER-VH tumors. Median rwPFS and rwTTC increased progressively with increasing ERα expression: ER-LI 10.6 and 14.3 months, ER-H 20.5 and 29.9 months, and ER–VH 28.5 and 40.6 months, respectively (p<0.001). PgR expression provide additional prognostic stratification with patients with ER-VH/PgR-high (≥20%) tumors having the longest median rwPFS (32.4 months; 95% CI 30.2-34.9), while those with ER-LI/PgR-low tumors had the shortest median rwPFS (8.3 months; 6.9-12). The authors conclude that effectiveness of first-line ET plus CDK4/6i worsens progressively with decreasing ERα expressions, and PgR expression adds further prognostic discrimination.