Long-term disease control and survival observed after stereotactic ablative body radiotherapy for oligometastatic breast cancer

Abstract

Purpose: We examined the characteristics of breast cancer patients with oligometastases (OM) treated with stereotactic ablative body radiotherapy (SABR) to identify factors associated with local progression, distant metastasis progression, time to subsequent therapy, progression-free survival (PFS), and overall survival (OS).

Methods: We retrospectively reviewed a single-institution database of patients treated with radiotherapy between 2008 and 2018 and identified 79 patients who received SABR to OM. Twenty-seven patients had genetic testing of metastatic tumors using an institutional targeted sequencing platform. Kaplan-Meier analysis, Cox regression, and competing risk models were used to compare clinical and genetic correlates with outcomes.

Results: Median follow-up was 50 months (IQR: 29-66) with 67% of patients alive at the last follow-up. Of the 65% of patients who progressed, 82% progressed outside of the radiation field, 18% experienced local failure, and 80% had oligoprogression. Median OS was 86 months (IQR: 29-66), and PFS was 33 months (IQR: 10-38). Less than 5 years from diagnosis to SABR and triple-negative breast cancer (TNBC) were associated with worse OS. Advanced T stage, any prior chemotherapy, and TNBC were associated with worse PFS. Alterations in CEBPB, RB1, TBX3, PTEN, and CDK4 were associated with worse survival outcomes.

Conclusion: Long-term systemic disease control and survival can be achieved with SABR for oligometastatic breast cancer. Hormone receptor-positive patients with a long disease interval from initial diagnosis and limited systemic progression history may be ideal for SABR to all sites of disease.

Keywords: breast cancer; metastasis; oligometastases; oncogenomics; radiation therapy; women's cancer.

FIGURE 1

Natural history of disease progression following SABR. In this swimmer plot, each patient is represented as a black line indicating the time from SABR until outcomes of interest. The time to the first progression is shown for patients who progressed (red) and those who did not progress (blue). For those patients who progressed, distant progression (black triangle) and local progression (white triangle) are shown. For all patients, death (black circle) and censoring (white circle) are also indicated. Of those who died, all patients except one were noted to have distant progression prior to death, indicating that death from any cause is not major a competing event for observing distant progression; whereas, many patients did not have observed local progression before death

FIGURE 2

Overall survival (OS) and progression‐free survival (PFS) by molecular subtype. A) Kaplan–Meier analysis of OS for the entire cohort demonstrates a median OS of 86 months (IQR: 29–66 months). A 95% confidence band is shown in gray. B) PFS for the entire cohort is shown with a median PFS of 33 months (IQR: 10–38 months). A 95% confidence band is shown in gray. C) OS is shown stratified by molecular subtype. HR+/HER2‐, HER2+, and TNBC had significantly different overall survival [log‐rank p=0.013]. Median OS for HR+/HER2‐, HER2+, and TNBC was 86 months (IQR: 31–60 months), 57 months (IQR: 9–59 months), and 18 months (IQR: 9–21 months), respectively. D) PFS is shown stratified by molecular subtype [log‐rank p=0.013]. The median PFS for HR+/HER2‐, HER2+, and TNBC was 36 months (IQR: 12–38 months), 57 months, (IQR: 9–59 months), and 5 months (IQR: 2–5 months), respectively

FIGURE 3

Forest plots indicating univariate (UVA) and multivariate (MVA) analyses for A) overall survival (OS) and B) progression‐free survival (PFS). The hazard ratios (HR) and 95% confidence intervals (CI) are shown. The reference (REF) categories for hazard ratios are indicated. OM refers to oligometastases. Only factors found to be significant in the UVA were included in the Cox proportional hazard MVA. For OS, the final model was stratified by molecular subtype and less time from diagnoses to SABR associated with worse OS. For PFS, having TNBC was associated with worse PFS compared to HR+/HER2‐ breast cancer

FIGURE 4

The 20 most frequently altered genes in the metastases of the subset of oligometastatic breast cancer patients who had target sequencing (n=27). Alterations include mutations and copy number aberrations (CNA). PIK3CA is the most frequently altered gene