Long-term Survival From Breast Cancer Brain Metastases in the Era of Modern Systemic Therapies

Abstract

BACKGROUND AND OBJECTIVES: Median survival for all patients with breast cancer with brain metastases (BCBMs) has increased in the era of targeted therapy (TT) and with improved local control of intracranial tumors using stereotactic radiosurgery (SRS) and surgical resection. However, detailed characterization of the patients with long-term survival in the past 5 years remains sparse. The aim of this article is to characterize patients with BCBM who achieved long-term survival and identify factors associated with the uniquely better outcomes and to find predictors of mortality for patients with BCBM. METHODS: We reviewed 190 patients with breast cancer with 931 brain tumors receiving SRS who were followed at our institution with prospective data collection between 2012 and 2022. We analyzed clinical, molecular, and imaging data to assess relationship to outcomes and tumor control. RESULTS: The median overall survival from initial SRS and from breast cancer diagnosis was 25 months (95% CI 19-31 months) and 130 months (95% CI 100-160 months), respectively. Sixteen patients (17%) achieved long-term survival (survival ≥5 years from SRS), 9 of whom are still alive. Predictors of long-term survival included HER2+ status (P = .041) and treatment with TT (P = .046). A limited number of patients (11%) died of central nervous system (CNS) causes. A predictor of CNS-related death was the development of leptomeningeal disease after SRS (P = .025), whereas predictors of non-CNS death included extracranial metastases at first SRS (P = .017), triple-negative breast cancer (P = .002), a Karnofsky Performance Status of <80 at first SRS (P = .002), and active systemic disease at last follow-up (P = .001). Only 13% of patients eventually needed whole brain radiotherapy. Among the long-term survivors, none died of CNS progression. CONCLUSION: Patients with BCBM can achieve long-term survival. The use of TT and HER2+ disease are associated with long-term survival. The primary cause of death was extracranial disease progression, and none of the patients living ≥5 years died of CNS-related disease.

Stereotactic Radiosurgery for Brain Metastases from Human Epidermal Receptor 2 Positive Breast Cancer: An International, Multi-center Study

“…ARE including radionecrosis are the most serious adverse event of SRS for brain metastases. In line with previous studies, symptomatic adverse radiation events occurred in 2.6% of the patients [3,30,31]. The current study suggests that concurrent use of pertuzumab (p < 0.001), and invasive lobular carcinoma primary (p = 0.042) increased the risk of overall but not of symptomatic adverse radiation effects.…”

“…At a median radiological follow up of 14.5 months, local progression occurred in 5.1% of the SRS-treated metastases in our series, similarly to previously reported local failure rates [31,34]. The local tumor control rate at six-, 12-, 24-, 36-and 60-months was 98%, 94%, 93%, 90%, and 88%, respectively.…”

“…Though SRS of brain metastases achieves high local tumor control, the six-and 12-months distant intracranial progression rate is high [3,7,9,31]. Overall intracranial progression occurred in 60% and leptomeningeal disease in 16.6% of the patients in our study.…”