Treatment Outcome in Women with Operable HER 2-Positive Breast Cancer: A single Institutional Report

Abstract

Purpose: Women with HER-2 overexpressing breast carcinoma benefit from trastuzumab-based systemic therapy despite the awareness of increasing risk of brain failure from this treatment modality among several studies. We report the treatment outcome and patterns of failure in women with operable HER2-positive breast cancer using trastuzumab as adjuvant setting at our institution, furthermore, focus on the incidence of central nervous system failure and the predictors for those with high risk of developing CNS relapse. Method and Material: We retrospectively identified 243 women with HER2-positive operable breast cancer diagnosed and treated at our institution between June 2002 and December 2011. All patients with tumor size more than two centimeters or any positive lymph node received adjuvant anthracycline-based chemotherapy with or without trastuzumab. Central nervous system failure was recognized through clinical symptoms and neuro-images during follow up. We estimated the event - free survival (EFS), overall survival (OS), and brain-metastasis free survival (BMFS) using Kaplan-Meier method, and performed cox-proportional hazards models to assess the impact of clinical-pathologic parameters on EFS, OS. The covariates for predicting CNS relapse either as first site or as sequential event during follow up were also analyzed. Results: With median follow up of 63.57 months (range 8.8~132.4months) of entire cohort, the five year event-free survival rate, overall survival rate, and brain-metastasis free survival was 72%, 85%, and 92%, respectively. Forty-three of sixty first events (71.7%) were distal relapse which remained the main failure type of our cohort. The five year cumulative incidence of different first events, included loco-regional recurrence, CNS relapse, distal non-CNS relapse, second primary, and non-cancer death, were 4.7%, 2.57%, 15.83%, 1.46%, and 0.4%. Central nervous system failure either as first site of recurrence or as a sequential event was noted in six and ten women. No adjuvant trastuzumab, positive lymph node number more than nine, and dermis involvement significantly predicted poorer event free survival on uni-and-multivariate analysis(p= 0.001, ＜ 0.001, 0.042, respectively). These factors also translated in predicting overall survival. No significant predictor was noted for the occurrence of CNS relapse as first site (5-year cumulative incidence: 1.86% and 3.02% in patients with or without adjuvant trastuzumab, p= 0.633). The negatively prognostic factors for brain-metastasis free survival were positive lymph node number more than nine, lymphovascular invasion, and high grade tumor (p= 0.043, ＜0.001, and ＜0.001, respectively). Conclusion: Using adjuvant trastuzumab improves event-free survival and overall survival in women with stage II /III HER2-positive breast cancer. The development of CNS relapse did not increase in our patients receiving trastuzumab based adjuvant therapy. Brain image as part of follow up might be considered, especially for those with positive lymph node number more than nine, high grade tumor, and with lymphovascular invasion. Larger prospective data or data from published randomized trials is needed for determining patients with high risks of developing CNS relapse.