BACKGROUND.The purpose of the current study was to characterize the outcomes of patients with metastatic triple‐negative breast cancers, including the risk and clinical consequences of central nervous system (CNS) recurrence.METHODS.Using pharmacy and pathology records, a study group of 116 patients who were treated for metastatic triple‐negative breast cancer at Dana‐Farber Cancer Institute between January 2000 and June 2006 was identified.RESULTS.The median survival from time of metastatic diagnosis was 13.3 months. Sixteen patients (14%) were diagnosed with CNS involvement at the time of initial metastatic diagnosis; overall, 46% of patients were diagnosed with CNS metastases before death. The median survival after a diagnosis of CNS metastasis was 4.9 months. The age‐adjusted and race‐adjusted rate of death for patients whose first presentation included a CNS metastasis was 3.4 times (95% confidence interval, 1.9‐6.1 times) that of patients without a CNS lesion at the time of first metastatic presentation. Of the 53 patients who developed brain metastases, only 3 patients were judged to have stable or responsive systemic disease in the face of progressive CNS disease at the last follow‐up before death.CONCLUSIONS.Triple‐negative breast cancer is associated with poor survival after recurrence. CNS recurrence is common, but death as a direct consequence of CNS progression in the setting of controlled systemic disease is uncommon. Thus, it does not appear that the high rate of CNS involvement is because of a sanctuary effect, but rather is due to the lack of effective therapies in general for this aggressive subtype of breast cancer. New treatment strategies are needed. Cancer 2008. © 2008 American Cancer Society.

Background Trastuzumab is associated with improvements in overall survival (OS) among patients with HER2-positive metastatic breast cancer (MBC); however disease course and patterns of care in individual patients are highly variable. Methods 113 HER2-positive patients diagnosed with MBC from 1999 to 2005 who received trastuzumab-based therapy were retrospectively identified to allow for a minimum of 5 years of follow-up time. Median OS and median duration of therapy were determined using Kaplan–Meier methodology and group comparisons were based on the log-rank test. Hazard ratios (HR) were obtained using a Cox proportional hazards model. Results Median OS was 3.5 years (95% CI 3.0–4.4) from time of initiation of first therapy in the metastatic setting. On univariate analysis, central nervous system (CNS) disease at first recurrence was associated with a shorter OS compared with liver and/or lung metastases or other sites (CNS: 1.9 years CI 0.1–5.9, liver/lung: 3.2 years CI 2.5–4.2, other: 4.6 years CI 2.7–8.0; p = 0.05), however, this was not predictive of survival outcome in multivariate analysis. CNS metastases developed in 62 (55%) patients by the time of death or last follow-up. Median duration of therapy was similar up to 6 lines of treatment, and ranged from 5.2 months to 7.2 months. Conclusions The natural history of HER2-positive MBC has evolved with trastuzumab-based therapy with median OS now exceeding 3 years. CNS disease is a major problem with continued risk of CNS progression over time. Patients demonstrate clinical benefit to multiple lines of HER2-directed therapy.

Many patients with MBC in both academic and community settings report willingness to consider undergoing biopsies for research. Further research is needed to understand ethical, logistical and provider-based barriers to broader participation in such studies.

Benefits of chemotherapy vary in patients with metastatic breast cancer (MBC). This article describes the impact of tumor subtype and the line of therapy on the duration of chemotherapy. Clinicopathologic characteristics were extracted from the medical records of 199 consecutive patients with MBC at Dana-Farber Cancer Institute and analyzed according to subtype. Tumor subtypes were classified as hormone receptor (HR)-positive, triple-negative (TNBC), or HER2-amplified breast cancer. Duration of chemotherapy of each line was defined as the start of a chemotherapy regimen to the start of the next line of therapy as a result of progression or toxicity. There were 96, 44, and 59 patients with HR(+), TNBC, and HER2-amplified breast cancer, respectively. Median age at MBC diagnosis was 53 years. Median overall survivals were 32 and 54 months for HER2-amplified disease, 36 months for HR(+) breast cancer, and 17 months for TNBC (P<.0001). Patients with HER2-amplified disease received the most lines (median, 4; P=.032) and the longest duration of chemotherapy for every line. The median duration of chemotherapy in HER2-amplified patients remained at more than 4 months even out to sixth-line therapy. Patients with TNBC tended to receive the shortest duration of chemotherapy for every line of therapy. Tumor subtypes influence the number of lines, duration of chemotherapy, and survival. Among patients with HR(+) and HER2-amplified disease who undergo chemotherapy beyond the third line, substantial rates of prolonged therapies suggest clinical benefit. The role of advanced (greater than third) chemotherapy lines in improving survival of all patients with MBC warrants further study.