Dose‐dense adjuvant chemotherapy in HER2‐positive early breast cancer patients before and after the introduction of trastuzumab: Exploratory analysis of the GIM2 trial.

Dose‐dense adjuvant chemotherapy is standard of care in high‐risk early breast cancer patients. However, its role in HER2‐positive patients is still uncertain. In this exploratory analysis of the GIM2 trial, we investigated the efficacy of dose‐dense chemotherapy in HER2‐positive breast cancer patients with or without exposure to trastuzumab. In the GIM2 trial, node‐positive early breast cancer patients were randomized to receive four cycles of (fluorouracil)epirubicin/cyclophosphamide followed by four cycles of paclitaxel administered every 2 (dose‐dense) or 3 (standard‐interval) weeks. After approval of adjuvant trastuzumab, protocol was amended in April 2006 to allow use of trastuzumab for 1 year after chemotherapy completion in HER2‐positive patients. The efficacy of dose‐dense chemotherapy in terms of disease‐free survival (DFS) and overall survival (OS) was assessed according to HER2 status and trastuzumab use. Out of 2,003 breast cancer patients, HER2 status was negative/unknown in 1,551 patients; among the 452 patients with HER2‐positive breast cancer, chemotherapy alone or followed by trastuzumab was given to 320 and 132 patients, respectively. Median follow‐up was 8.1 years. No significant interaction between HER2 status, trastuzumab use and chemotherapy treatment was observed for both DFS (p = 0.698) and OS (p = 0.708). Nevertheless, there was no apparent benefit in the HER2‐positive group treated with trastuzumab (DFS: HR, 0.99; 95% CI 0.52–1.89; OS: HR, 0.95; 95% CI 0.37–2.41). Although dose‐dense chemotherapy was associated with a significant survival improvement in high‐risk breast cancer patients, its benefit appeared to be smaller (if any) in patients with HER2‐positive disease who received adjuvant trastuzumab. What's new? Dose‐dense chemotherapy is standard of care in high‐risk early breast cancer; however, its role in HER2‐positive patients is still uncertain. In this exploratory analysis of the GIM2 trial, we showed that the benefit of dose‐dense chemotherapy appeared to be small (if any) in HER2‐positive patients who received trastuzumab raising concerns on the need of chemotherapy escalation approaches in this setting. These findings may guide the choice of adjuvant chemotherapy in HER2‐positive early breast cancer patients. [ABSTRACT FROM AUTHOR]