Effect of Primary Breast Surgery on Prognosis in Breast Cancer Patients Presenting with Isolated Bone Metastases

Abstract

Background: Breast cancer with isolated bone metastases at initial diagnosis represents a clinically distinct metastatic phenotype, often associated with more indolent biology and relatively favorable outcomes compared with visceral metastatic disease. The survival impact of resecting the intact primary breast tumor in de novo metastatic breast cancer remains controversial. In this study, we evaluated the association between primary breast surgery and overall survival (OS), defined as the time from diagnosis to death attributable to breast cancer, in patients presenting with isolated bone metastatic breast cancer. Methods: We performed a retrospective population-based cohort study using the Surveillance, Epidemiology, and End Results (SEER) database. Because the SEER variable for bone metastasis at diagnosis is available from 2010 onward and HER2-defined subtype information is available in the modern SEER era, the effective study period was defined as 2010-2021 rather than the full 2000-2021 SEER release period. Patients with breast cancer and isolated bone metastases at presentation, without evidence of lung, liver, brain, or other distant metastatic sites at diagnosis, were included. Demographic and clinicopathological variables, including age, sex, race, biologic subtype, histology, chemotherapy, radiotherapy, and primary breast surgery, were analyzed. Overall survival (OS), defined as the time from diagnosis to death attributable to breast cancer, was estimated using Kaplan-Meier methods and compared using the log-rank test. Independent prognostic factors were evaluated using multivariable Cox proportional hazards modeling. Results: A total of 6500 eligible patients were identified. Surgery of the primary breast tumor was performed in 1513 (23.3%) patients, and 62.8% received chemotherapy. Five-year overall survival (OS) was significantly higher among patients who underwent surgery than among those who did not undergo surgery (59.5% vs. 38.6%; p < 0.001). In multivariable analysis, primary breast surgery remained independently associated with improved OS (hazard ratio [HR] 0.54, 95% CI 0.48-0.62; p < 0.001). Age, histology, chemotherapy, radiotherapy, and biologic subtype were also associated with prognosis. Sex was not significant in the unadjusted analysis (p = 0.188), and the multivariable sex finding was interpreted cautiously because only 96 men were included. Conclusions: In this population-based cohort of patients with de novo breast cancer and isolated bone metastases, primary breast surgery was associated with improved survival among selected patients. However, this association should not be interpreted as causal, given the inherent limitations of observational registry data, including treatment selection, potential immortal-time bias, unmeasured metastatic burden, performance status, systemic therapy type and response, and local symptom burden, which are not fully captured in SEER. These findings support careful multidisciplinary consideration of local therapy in selected patients, while emphasizing the need for confirmation in prospectively designed studies.