263PD - Time to Initiation of Adjuvant Chemotherapy in Patients with Rapidly Proliferating Early Breast Cancer

Abstract

ABSTRACT Introduction: The optimal time from surgery to commencing chemotherapy in early breast cancer (EBC) remains unclear. We assessed the influence of time to initiation of adjuvant chemotherapy (TTC) on the outcome of EBC patients enrolled onto a phase III clinical trial (NCT01031030). Methods: The relationship between TTC, calculated as the time (in weeks) from definitive surgery to initiation of adjuvant chemotherapy, and disease-free (DFS) or overall survival (OS) was assessed in 1066 EBC patients with rapidly proliferating tumors (thymidine labeling index > 3% or G3 or Ki67 > 20%), randomized to receive adjuvant chemotherapy with or without anthracyclines (epirubicin → CMF vs CMF → epirubicin vs CMF). DFS, OS and their 95% confidence intervals (95% CI) were calculated by the Kaplan-Meier method. Multivariate Cox analysis was performed in relation to nodal involvement, estrogen receptor and HER2 status, Ki67 value, type of adjuvant chemotherapy, menopausal status and tumor size. Results: Information on TTC was available for 713 women. At a median follow-up of 105 months (range 2-188), a prolonged TTC resulted in a significant increase of 16% in the risk of relapse (95% CI 1.03–1.30, p = 0.016) in a multivariable Cox regression model (Table 1). The impact on OS was not significant. Using a backward elimination procedure, TTC, tumor size and nodal involvement remained significantly associated with DFS (Hazard ratio [HR] = 1.15, 95% CI 1.02-1.29, p = 0.018; HR = 1.44, 95% CI 1.08-1.92, p = 0.012; HR = 1.44, 95% CI 1.08-1.92, p = 0.012, respectively). Again, nodal involvement and Ki67 were associated with OS (HR = 1.66, 95% CI 1.11-2.49, p = 0.014; HR = 1.63, 95% CI 1.03-2.59, p = 0.039, respectively). DFS OS HR (95% CI) p HR (95% CI) p TTC 1.16 (1.03–1.30) 0.016 1.14 (0.97–1.35) 0.121 Age 0.99 (0.97–1.02) 0.829 0.99 (0.96–1.03) 0.615 ER Positive 1.00 1.00 Negative 1.20 (0.89–1.61) 0.242 1.20 (0.78–1.84) 0.397 HER2 Positive 1.00 1.00 Negative 0.99 (0.73–1.33) 0.929 0.92 (0.60–1.42) 0.713 Lymph node status Negative 1.00 1.00 Positive 1.53 (1.14–2.04) 0.004 1.71 (1.13–2.59) 0.011 Menopausal status Premenopausal 1.00 1.00 Postmenopausal 1.32 (0.85–2.04) 0.219 1.56 (0.82–2.97) 0.177 Tumor size 1.00 1.00 ≥2 cm 1.41 (1.05–1.88) 0.020 1.44 (0.95–2.18) 0.085 Ki67 ≤20% 1.00 1.00 >20% 1.06 (0.77–1.44) 0.724 1.54 (0.96–2.48) 0.073 Treatment arm E»CMF 0.72 (0.49–1.04) 0.079 0.69 (0.41–1.16) 0.161 CMF»E 0.79 (0.55–1.14) 0.202 0.75 (0.45–1.25) 0.273 CMF 1.00 1.00 Conclusions: Our results suggest that patients with rapidly proliferating EBC should be treated as soon as possible once their recovery from surgery is complete. Disclosure: All authors have declared no conflicts of interest.