Effect of Tumor Subtype on Survival and the Graded Prognostic Assessment for Patients With Breast Cancer and Brain Metastases

Abstract

BACKGROUND The diagnosis-specific Graded Prognostic Assessment (GPA) was published to clarify prognosis for patients with brain metastases. This study refines the existing Breast-GPA by analyzing a larger cohort and tumor subtype. METHODS A multi-institutional retrospective database of 400 breast cancer patients treated for newly-diagnosed brain metastases was generated. Prognostic factors significant for survival were analyzed by multivariate Cox regression (MCR) and recursive partitioning analysis (RPA). Factors were weighted by the magnitude of their regression coefficients to define the GPA index. RESULTS Significant prognostic factors by MCR and RPA were Karnofsky Performance Status (KPS), HER2, ER/PR status, and the interaction between ER/PR and HER2. RPA showed age was significant for patients with KPS 60–80. The median survival time (MST) overall was 13.8 months, and for GPA scores of 0–1.0, 1.5–2.0, 2.5–3.0 and 3.5–4.0 was 3.4 (n=23), 7.7 (n=104), 15.1 (n=140) and 25.3 (n=133) months, respectively (p < 0.0001). Among HER2-negative patients, being ER/PR-positive improved MST from 6.4 to 9.7 months whereas in HER2-positive patients, being ER/PR-positive improved MST from 17.9 to 20.7 months. The log-rank statistic (predictive power) was 110 for the Breast-GPA versus 55 for tumor subtype. CONCLUSIONS The Breast-GPA documents wide variation in prognosis and shows clear separation between subgroups of patients with breast cancer and brain metastases. This tool will aid clinical decision-making and stratification of clinical trials. These data confirm the effect of tumor subtype on survival and show the Breast-GPA offers significantly more predictive power than the tumor subtype alone.

Survival among patients with 10 or more brain metastases treated with stereotactic radiosurgery

“…In our analysis, the only variable that approached significance was breast cancer histological type, and although only 14% of all other patients survived longer than 1 year, > 40% of patients with metastatic breast cancer survived more than 1 year. Sperduto et al 21 reported on risk grouping among women with breast cancer and brain metastases that was based on hormone receptor status as well as Her2-neu and predicted median survival between 9.1 and 26.8 months. Our cohort is too small for such an analysis, however, and although these criteria were developed for patients with newly diagnosed brain metastases, they may be helpful for predicting survival in patients with multiple recurrent brain metastases as well.…”

Brain metastases from breast cancer: lessons from experimental magnetic resonance imaging studies and clinical implications

“…Risk of brain metastasis is high for patients who (1) are young, (2) have lymph node-positive disease and/or other systemic metastases, (3) are diagnosed with "triple-negative" breast cancer (ER-, PR-, HER2 unamplified), and/or whose tumors (4) overexpress HER2 [13,14]. In patients with the HER2-positive metastatic breast cancer, the frequency of brain metastasis has been reported to be as high as 50 % [15]. Brain metastases have emerged as a major challenge affecting morbidity and mortality of patients with HER2-positive metastatic breast cancer [16].…”

Role of targeted therapy in the treatment of HER-2-positive breast cancer brain metastases

“…При этом более половины больных HER-2 + РМЖ с метастазами в ГМ живут относительно долго [12]. Метастазирование в ГМ у пациентов с РМЖ является катастрофическим событием, предсказывающим пло-хой прогноз; медиана выживаемости, несмотря на ле-чение, колеблется от 2 до 25,3 мес [13,14]. Кроме того, метастазы данной локализации являются основной причиной прогрессирующих неврологических рас-стройств, приводящих к снижению качества жизни [15].…”