Clinical and biomarker predictors of early and late recurrence in hormone receptor-positive breast cancer

Abstract

Background: Hormone receptor-positive (HR+) breast cancer (BC) is characterized by a persistent risk of recurrence that continues for decades. Although many factors have been linked to recurrence, the clinical features associated with late relapse and patterns of distant metastases are less understood. Our study aimed to identify factors associated with early (< 5 years) and late (5–10 years) recurrence in a real-world cohort of HR+/human epidermal growth factor receptor type2-negative (HER2-) BC patients. Methods: Our study performed a retrospective analysis of stage I-III HR+/HER2- BC cases diagnosed between 1981 and 2022. Assessed variables included metastatic sites, early and late invasive recurrences. Results: A total of 4,367 women with HR+/HER2- were included; 81.2% were stage I/II, 41,4% had nodal involvement; 42.0% received neoadjuvant chemotherapy and 94.0% adjuvant endocrine therapy (ET). Five- and ten-year invasive disease-free survival (iDFS) rates were 85.0% and 70.0%, respectively. Of the 847 invasive events (19.4%), 54.3% were early and 45.7% late recurrences. Compared with late recurrences, early recurrences were associated with fewer stage I tumors, higher nodal involvement, higher grade, and elevated Ki-67. In multivariate analysis, higher stage was the only independent factor linked to both early and late recurrence; older age correlated with late relapse. Distant metastases occurred in 70.2% of recurrences and were associated with higher tumor burden, grade 3, and elevated Ki-67; 47.5% involved visceral sites. Conclusion: Late recurrences may occur even in patients clinically classified as low risk. Early recurrences reflect higher tumor burden and proliferative activity, with implications for treatment and follow-up strategies.