Distinct ER and PR expression patterns significantly affect the clinical outcomes of early HER2-positive breast cancer: A real-world analysis of 871 patients treated with neoadjuvant therapy

IntroductionThe impact of distinct tumor estrogen receptor (ER) and progesterone receptor (PR) expression patterns on tumor behavior and treatment outcomes within HER2-positive breast cancer is not fully explored. This study aimed to comprehensively examine the clinical differences among patients with HER2-positive breast cancer harboring distinct ER and PR expression patterns in the neoadjuvant setting.MethodsThis retrospective analysis included 871 HER2-positive breast patients treated with neoadjuvant therapy at our hospital between 2011 and 2022. Comparisons were performed across the three hormone receptor (HR)-specific subtypes, namely the ER-negative/PR-negative/HER2-positive (ER-/PR-/HER2+), the single HR-positive (HR+)/HER2+, and the triple-positive breast cancer (TPBC) subtypes.ResultsOf 871 patients, 21.0% had ER-/PR-/HER2+ tumors, 33.6% had single HR+/HER2+ disease, and 45.4% had TPBC. Individuals with single HR+/HER2+ tumors and TPBC cases demonstrated significantly lower pathological complete response (pCR) rates compared to those with ER-/PR-/HER2+ tumors (36.9% vs. 24.3% vs 49.2%, p<0.001). Multivariate analysis confirmed TPBC as significantly associated with decreased pCR likelihood (OR=0.42, 95%CI 0.28-0.63, p<0.001). Survival outcomes, including disease-free survival (DFS) and overall survival (OS), showed no significant differences across HR-specific subtypes in the overall patient population. However, within patients without anti-HER2 therapy, TPBC was linked to improved DFS and a trend towards better OS.ConclusionsHER2-positive breast cancer exhibits three distinct HR-specific subtypes with varying clinical manifestations and treatment responses. These findings suggest personalized treatment strategies considering ER and PR expression patterns, emphasizing the need for further investigations to unravel molecular traits underlying HER2-positive breast cancer with distinct HR expression patterns.