Clinical impact of delaying initiation of adjuvant chemotherapy in patients with breast cancer

Abstract

Purpose: For patients with breast cancer (BC), the optimal time to initiation of adjuvant chemotherapy (TTC) after definitive surgery is unknown. We evaluated the association between TTC and survival according to breast cancer subtype and stage at diagnosis.

Patients and methods: Women diagnosed with BC stages I to III between 1997 and 2011 who received adjuvant chemotherapy at our institution were included. Patients were categorized into three groups according to TTC: ≤ 30, 31 to 60, and ≥ 61 days. Survival outcomes were estimated and compared according to TTC and by BC subtype.

Results: Among the 6,827 patients included, the 5-year overall survival (OS), relapse-free survival (RFS), and distant RFS (DRFS) estimates were similar for the different TTC categories. Initiation of chemotherapy ≥ 61 days after surgery was associated with adverse outcomes among patients with stage II (DRFS: hazard ratio [HR], 1.20; 95% CI, 1.02 to 1.43) and stage III (OS: HR, 1.76; 95% CI, 1.26 to 2.46; RFS: HR, 1.34; 95% CI, 1.01 to 1.76; and DRFS: HR, 1.36; 95% CI, 1.02 to 1.80) BC. Patients with triple-negative BC (TNBC) tumors and those with human epidermal growth factor receptor 2 (HER2) -positive tumors treated with trastuzumab who started chemotherapy ≥ 61 days after surgery had worse survival (HR, 1.54; 95% CI, 1.09 to 2.18 and HR, 3.09; 95% CI, 1.49 to 6.39, respectively) compared with those who initiated treatment in the first 30 days after surgery.

Conclusion: TTC influenced survival outcomes in the overall study cohort. This finding was particularly meaningful for patients with stage III BC, TNBC, and trastuzumab-treated HER2-positive tumors who experienced worse outcomes when chemotherapy was delayed. Our findings suggest that early initiation of chemotherapy should be granted for patients in these high-risk groups.