Prognostic factors of survival in the trastuzumab era among women with breast cancer and brain metastases who receive whole brain radiotherapy

Abstract

BACKGROUND:The objective of this study was to review the outcome of women with breast cancer with known receptor status who were treated with whole brain radiotherapy for brain metastases and to determine factors that impact survival. METHODS: A total of 223 women with breast cancer and brain metastases, who received whole brain radiotherapy, were identified. All women with HER-2-positive disease had received trastuzumab. Kaplan-Meier product limit method was used to determine overall survival (OS) estimates. Cox proportional hazards models were then fitted to explore the association of OS with various patient and tumor characteristics. RESULTS: Median age at brain metastases diagnosis was 50 years. Sixty-seven (30.2%) patients had hormone receptor-positive/HER-2-negative disease, 101 (45.50%) had HER-2-positive disease, and 54 (24.3%) had triple receptor-negative disease. Median OS from brain metastases was 6 months, with 1-year survival of 30% (95% confidence interval [CI], 23%-36%). Women with hormone receptor-positive/HER-2-negative, HER-2-positive, and triple-negative tumors had median survivals of 5, 9, and 5 months, respectively (P ¼.0069). In the multivariate model, women with HER-2-positive disease had a significantly decreased risk of death compared with women with hormone receptor-positive/HER-2-negative disease (hazard ratio, 0.63; 95%CI, 0.42-0.94; P ¼.02). The risk of death among women with triple-negative disease compared with hormone receptor-positive/HER-2-negative disease was not significantly different (P ¼.54). Lower recursive partitioning analysis class and 30-gray brain radiation dose were also significantly associated with a decreased risk of death. CONCLUSIONS: Breast tumor subtype has a significant prognostic role among women with breast cancer and brain metastases. In addition, in the trastuzumab era factors such as recursive partitioning analysis and adequate radiation dose continue to be important prognostic factors. Cancer 2010;116:3084-92.

Radiotherapy of brain metastases from breast cancer: Treatment results and prognostic factors

“…In comparison to other data in the literature, this interval is slightly shorter; median survival times between 4.5 and 10 months have been reported (12)(13)(14)(15)(16).…”

“…In the present cohort, surgical resection was typically performed in patients with a solitary brain metastasis. It is well established that a smaller number of BM is associated with longer survival (7,14,15,23). In the present cohort, the group of patients that underwent surgical resection was very small.…”

The effect of tumor subtype on survival and the graded prognostic assessment (GPA) for patients with breast cancer and brain metastases.

“…Although there have been conflicting findings, numerous variables have been shown to have some prognostic value including the following: Basal subtype (20,21,51); whole brain radiation dose of greater than or equal to 30 Gy (20,22); KPS (19,(22)(23)(24)(25)(26)(27)(28)(29)(30); presence/degree of extracranial metastases (21-23,27,30,31); primary tumor control (24,32); size of primary tumor (22); interval from first cancer diagnosis to brain metastases (23); number of brain metastases (22,23,32,33); solitary metastasis (22,34); age (19,21,24,30,34); ER status (21,24,26); HER2 expression (22,24,29,30,32,35); systemic chemotherapy (28); lymphopenia (29,36); and surgical resection (28,31).…”

“…However, they acknowledge the shortcomings of their model and state, "Without doubt, the definitive prognostic score can only be created from a very large database." Other groups have also confirmed the prognostic value of the RPA system (20,29,31,37) and SIR in terms of survival (19,26). Le Scodan created a prognostic system based on the variables found to be statistically significant in their analysis however this was a small study (n=117) from a single institution, treated with WBRT alone (29).…”

“…Multiple studies have demonstrated tumor subtype affects prognoses (16)(17)(18), however, neither the RTOG-RPA classification system nor the current Breast-Specific GPA system include tumor subtype in their models. Many other authors have described other prognostic factors, albeit with conflicting findings (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37). Gaspar et al published a seminal work on a prognostic index for patients with brain metastases, the Radiation Therapy Oncology Group's Recursive Partitioning Analysis (RTOG-RPA) in 1997 (38).…”