Long-term Disease Control and Survival Observed after Stereotactic Body Radiotherapy for Oligometastatic Breast Cancer

Abstract

Despite the increasing frequency of stereotactic body radiotherapy (SBRT) in the management of patients with oligometastases (OM), there is limited data on patient selection and treatment outcomes. We examined the clinical and molecular characteristics of OM breast cancer patients treated with ablative SBRT to remaining sites of disease and sought to identify factors associated with progression free survival (PFS) and overall survival (OS). We retrospectively reviewed a single-institution database of breast cancer patients who received SBRT to metastases between 2008 and 2018, and we identified 91 patients with OM breast cancer, defined as 5 or fewer extracranial metastases, who received SBRT to all metastases. Patients who received prior conventional RT to metastases were excluded. Of the study cohort, 38 patients had genetic testing of metastatic tumors using an institutional targeted sequencing platform that examines 341 to 468 genes. The presence of any mutation within a gene exon or copy number change was noted. Kaplan-Meier analysis was used to assess OS and PFS. Univariate and multivariate (MVA) Cox regression models were used to compare clinical and genetic correlates of PFS and OS after SBRT. Median follow-up was 41 months (2-113 months) with 71% of patients alive at the last follow-up. The median patient age was 55 (30-89 years), and most patients (79%) had ER+/HER2- breast cancer (12% ER+/HER2+, 8% ER-/HER2-, 1% ER-/HER2+). Most patients received SBRT to 1 oligometastatic site (80%) with osseous metastases as the most common site of disease (92%). The median time to progression after RT was 36 months (2-91 months). PFS and OS of the study cohort at 36 months was 47% and 83%, respectively. Of the patients who progressed (n=43), 84% developed new metastases and 16% experienced local failure at the SBRT site. On MVA, ER- was associated with worse PFS compared to other subtypes (HR=2.7, p=0.03) with PFS of 43% at 36 months for ER-/HER2- (vs. ER+/HER2- 53%, p=0.05). For OS, younger patients (HR=1.1/year, p=0.05), ER- (HR=9.9, p<0.001), and shorter interval from breast cancer diagnosis (HR=1.1/year, p=0.02) were independently associated with worse survival on MVA. At 36 months, OS of patients with ER-/HER2- breast cancer vs. patients with ER+/HER2- breast cancer was 38% and 90% (p=0.04). Patients with GATA3 alterations (18%) compared to those without had worse PFS (HR=3.0, p=0.04) with median PFS of 5 months vs. 25 months. No genetic mutations associated with OS were identified. Long-term systemic disease control and survival can be achieved with SBRT for oligometastatic breast cancer. Despite patients with ER-/HER2- breast cancer having worse clinical outcomes, we found a promising 43% of patients living without disease progression at 3 years after SBRT in this patient population. A prospective study elucidating the benefit of SBRT for OM in patients with ER-/HER2- breast cancer and genetic predictors of response, such as GATA3, is warranted.