Clinical outcomes and treatment practice patterns of patients with HER2-positive metastatic breast cancer in the post-trastuzumab era

Abstract

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.

Fig. 1

Identification of patients used in study. Abbreviations: ICD-9, International Classification of Diseases 9th Edition; DFCI, Dana-Farber Cancer Institute; IHC, immunohistochemistry; FISH, florescence in situ hybridization; EMR, electronic medical record.

Fig. 2

Kaplan–Meier product-limit overall survival estimate for all patients in cohort.

Fig. 3

Hazard function of death for all patients in cohort.

Fig. 4

a) Distribution of all patients by total number of metastatic regimens administered over the course of the follow-up period. b) Median duration of therapy on each metastatic regimen from the first-line of therapy to up to 6 lines of therapy. Duration of therapy was defined from initiation of treatment to initiation of subsequent regimen; for patients continuing on treatment, times were censored at date of last visit.