Impact of delaying initiation of adjuvant chemotherapy and trastuzumab in patients with early-stage HER2-positive breast cancer.

Abstract

e12033 Background: About 20% of breast cancers harbor an amplification and/ or overexpression of human epidermal growth factor receptor 2 (HER2).The treatment of HER2-positive BC combined of chemotherapy and Trastuzumab, results in reduction of disease recurrence in half. However, the optimal timing for adjuvant chemotherapy initiation is unclear. Methods: Retrospective chart review of 226 HER2-positive early-stage BC patients diagnosed between November 2002-May 2014 treated with adjuvant chemotherapy and Trastuzumab was obtained. Patients' average age was 54 years. Bivariate and multivariate analyses were performed to assess optimal timing for treatment initiation from primary diagnosis (obtained by tissue biopsy) and surgery. Primary endpoint was disease recurrence (locoregional/distant metastases). Other analysis included disease free survival (DFS), breast cancer specific survival (BCSS) and overall survival (OS). Results: Among 226 patients, 28 patients (12% of all patients) started Trastuzumab more than 36 weeks from primary diagnosis. The influence of a delay in treatment initiation was more profound as risk factors' number (e.g. stage, histopathological grade, positive lymph node status) increased, particulary with positive lymph nodes or a higher stage. 5-year disease free survival rates (DFS) in patients who had started Trastuzumab within than 36 weeks from diagnosis were: 93% in patient with 0-1 risk factors; 75% in patients with 2 risk factors; 77% in patients with 3-4 risk factors, and DFS rate dropped to 50% when Herceptin was initiated more than 36 weeks from diagnosis in patients with 3-4 risk factors. A higher disease recurrence rate (HR = 3.2 , p= 0.005,) was found in this subgroup, with highest negative impact in patients with stage III BC. A delay of more than 12 weeks from primary diagnosis to chemotherapy initiation in specific subgroups was attributed to a worse prognosis. The influence of treatment delay was more profound in patients with higher number of risk factors (e.g. stage, grade, positive lymph node (LN) status), particularly with positive LN or a higher stage. Conclusions: Delay in Trastuzumab initiation has a crucial negative influence upon DFS and OS rates, especially in specific subgroups with more risk factors. Delay of more than 12 weeks from primary diagnosis obtained by tissue biopsy to chemotherapy initiation may be associated with a worse prognosis.