Outcomes of Women with Early Stage HER2 Overexpressing Breast Cancer Receiving Adjuvant Trastuzumab: A Population Based Analysis.
Authors: M. Seal, C. Speers, K. Gelmon, K. Gelmon, S. Ellard, R. Pickering, S. O'Reilly, S. Chia, S. Chia
Journal: Cancer Research (2009)

Abstract Background: Approximately 15% of early breast cancers have amplification of the human epidermal receptor-2 (HER-2) gene, which portends a poor prognosis. Large randomized trials assessing the benefit of adjuvant trastuzumab in early stage HER-2+ breast cancer have demonstrated a 50% reduction in disease recurrence and a 30% improvement in survival. This prompted the widespread use of trastuzumab (T) in clinical practice in 2005. The objective of this study was to describe the utilization and outcomes of women who received adjuvant trastuzumab for HER-2 positive breast cancer in British Columbia since publicly funded population based use was initiated in July 2005.Methods: Women with stage I-III breast cancer positive for HER-2 overexpression by immunohistochemistry (3+) or amplification by fluorescence in situ hybridization (ratio ≥ 2.0) diagnosed from July 2004 to December 2006 were included in this study. Demographic information, tumour characteristics and outcomes on all identified patients were obtained from the BCCA Breast Cancer Outcomes Unit database. Cases were matched with the provincial BCCA pharmacy data repository to determine the proportion of women who received adjuvant T and to differentiate groups according to type of systemic treatment, including sequential versus concurrent chemotherapy (CT) with T. Kaplan-Meier curves were used to illustrate survival outcomes.Results: 704 HER-2 positive patients were identified in this retrospective study. 68% (n=480) received T. Nearly 100% of patients receiving adjuvant T underwent chemotherapy versus 28% of patients who did not receive T (n=224). The majority of patients received T concurrent with CT (71%) versus sequentially (29%). Median follow-up was 2.1 years.Two-year relapse-free survival (RFS) in patients receiving trastuzumab was 95.9% (95% CI, 93.4-97.5) and overall survival (OS) was 99.3% (95% CI, 97.9-99.8). First site of distant metastases was brain in 17.8% of relapsing patients (35% of relapsing patients who received T). The 2-year RFS among patients receiving concurrent chemotherapy + T was 94.7% whereas sequential CT followed by T was 98.4%. In the T treated cohort, the 2-year RFS rates among node negative and node positive patients were 97.8% and 94.4% respectively (p=0.06). In the cohort of HER-2 positive patients who did not receive T, the 2-year RFS rates among node negative and node positive patients were 90.7% and 75.5% respectively (p=0.007). The corresponding 2-year distant RFS in this same cohort was 93.1% and 80.3% respectively (p=0.01).Conclusions: A population based analysis of adjuvant trastuzumab use among Canadian women demonstrates highly favorable outcomes at the 2 year follow-up period. Although retrospective in nature, this is one of the first studies to observe breast cancer outcomes in a more generalized population with widespread publicly funded use of trastuzumab. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5086.