Treatment Patterns and Outcomes of Women with Symptomatic and Asymptomatic Breast Cancer Brain Metastases: A Single-Center Retrospective Study

Abstract

Background. Breast cancer is the most common cancer among women worldwide, and the second leading cause of brain metastases (BrM). We assessed the treatment patterns and outcomes of women treated for breast cancer BrM at our institution in the modern era of stereotactic radiosurgery (SRS). Materials and Methods. We conducted a retrospective analysis of women (≥ 18 years old) with metastatic breast cancer who were treated with surgery, whole brain radiotherapy (WBRT) or SRS to the brain at the Sunnybrook Odette Cancer Center, Toronto, Canada between 2008 and 2018. Patients with a history of other malignancies and those with an uncertain date of diagnosis of BrM were excluded. Descriptive statistics were generated and survival analyses were performed, with subgroup analyses by breast cancer subtype.Results. Among 683 eligible patients, 153 (22.4%) had triple negative (TNBC), 188 (27.5%) had HER2+, 246 (36.0%) had hormone receptor (HR)+/HER2-, and 61 (13.3%) had breast cancer of unknown subtype. The majority of patients received fist line WBRT (n=459, 67.2%) or SRS (n=126, 18.4%). The median brain-specific progression-free survival and median overall survival (OS) were 4.1 months (IQR 1.0-9.6 months) and 5.1 months (IQR 2.0-11.7 months) in the overall patent population, respectively. Age >60 years, presence of neurological symptoms at BrM diagnosis, first line WBRT and HER2-subtype were independently prognostic for shorter OS. Conclusion. Despite the use of SRS, outcomes among patients with breast cancer BrM remain poor. Strategies for early detection of BrM and central nervous system-active systemic therapies warrant further investigation. The Oncologist 2021;9999:• • Implications for Practice: Although triple negative and HER2+ breast cancer have a predilection for metastasis to the central nervous system (CNS), patients with hormone receptor (HR)+/HER2-breast cancer represent a high proportion of patients with breast cancer brain metastases (BrM). Hence, clinical trials should include patients with BrM and evaluate CNS-specific activity of novel systemic therapies when feasible, irrespective of breast cancer subtype. In addition, given that symptomatic BrM are associated with shorter survival, we propose that screening programs for the early detection and treatment of breast cancer BrM warrant further investigation in an era of minimally toxic stereotactic radiosurgery.

Comprehensive Analysis of the Immunogenomics of Triple-Negative Breast Cancer Brain Metastases From LCCC1419

“…We examined the survival association of standard clinicopathological variables (age at diagnosis of primary tumor, stage, and race) with different time metrics to event: (1) time from diagnosis of primary TNBC to death, (2) time from diagnosis of any metastatic disease to death, and (3) time from diagnosis of BrM to death. Of these variables, only older age was significantly associated with poor survival using each of these time metrics ( Supplementary Figure S10 ), which was similar to other recent reports ( 70 , 71 ). Next, survival associations relative to IGS expression were evaluated using multivariable CoxPH models in both primary TNBC and BrM.…”

Karnofsky Performance Status (KPS) ≤60 Is Strongly Associated With Shorter Brain-Specific Progression-Free Survival Among Patients With Metastatic Breast Cancer With Brain Metastases

“…Once KPS was accounted for, none of the other variables examined were significantly associated with bsPFS in our multivariable analysis. This is likely due to an intimate connection between KPS and other variables that are associated with bsPFS ( 9 ). Increasing age is associated with higher burdens of comorbidity and greater frailty, which tend to lead to diminishing functional abilities and therefore lower KPS.…”

“…We used a previously established cohort of 683 individuals who underwent radiotherapy and/or metastasectomy for BrM from 2008-2018 at Sunnybrook Health Sciences Centre in Toronto, Canada. Details regarding the cohort and baseline characteristics of included patients have been previously outlined ( 9 ). All factors found to be significantly associated with bsPFS or OS in the Sperduto et al ( 8 ) or Gao et al ( 9 ) studies were included in this analysis.…”

“…Details regarding the cohort and baseline characteristics of included patients have been previously outlined ( 9 ). All factors found to be significantly associated with bsPFS or OS in the Sperduto et al ( 8 ) or Gao et al ( 9 ) studies were included in this analysis. These included KPS, age, tumour receptor status, presence of leptomeningeal disease, presence of neurological symptoms, number of BrM, location of extracranial metastases, and initial treatment modality for BrM.…”

“…Unfortunately, patients with MBC and brain metastases ("BrM") have poor outcomes compared to those without BrM (5)(6)(7)(8)(9). While blood-brain-barrier-crossing HER2-targeted therapies (10) and SRS (2,3,11) have improved outcomes for these patients, they continue to suffer from high rates of morbidity and mortality (12,13), often driven by neurocognitive sequelae of their intracranial metastatic disease (14)(15)(16).…”