Clinical effect of bisphosphonate in patients with hormone receptor-positive early breast cancer: A nationwide real-world data analysis

Background: Adjuvant bisphosphonates (BPs) improve survival in early breast cancer (EBC), particularly among postmenopausal women.However, in Korea, BPs are primarily reimbursed for osteoporosis, limiting their application as adjuvant cancer therapy.This nationwide real-world study aimed to evaluate the impact of BP use on survival and fracture outcomes in Korean women with hormone receptor-positive (HR+) EBC. Methods:We identified 52,599 women diagnosed with HR+ EBC between 2012 and 2019 from the Korea Central Cancer Registry, who underwent surgery and initiated endocrine therapy.BP users (n=4,800) were defined as those prescribed BPs for 1-year post-diagnosis.Outcomes included overall survival (OS), recurrence-free survival (RFS), fracture incidence, and fracture-free survival (FFS).Multivariate Cox models incorporating age stratifications and landmark analyses were further applied.Findings: BP use was significantly associated with improved OS.Although the overall RFS was not significant, patients aged 60 years showed significant improvements in both OS and RFS.Longer BP exposure (3 years) demonstrated consistent OS benefits across the 1-, 2-, and 3-year landmark analyses.Although fractures were higher in BP users, reflecting confounding by indication, age-stratified FFS suggested a potential protective effect against fractures in older patients (73 years).Interpretation: BP therapy was associated with improved OS and age-dependent (60 years) benefits in HR+ EBC.Despite higher fracture rates in BP users, age-stratified analyses suggest a fracturepreventive signal in older patients.These findings support adjuvant BP use in selected postmenopausal/high-risk subgroups.Prospective studies are needed to optimize BP timing and duration in this population.