263PD - Time to initiation of adjuvant chemotherapy in patients with rapidly proliferating early breast cancer

Date 27 September 2014
Event ESMO 2014
Session Breast cancer, early stage
Topics Anti-Cancer Agents & Biologic Therapy
Breast Cancer, Early Stage
Presenter Alberto Farolfi
Citation Annals of Oncology (2014) 25 (suppl_4): iv85-iv109. 10.1093/annonc/mdu327
Authors A. Farolfi, E. Scarpi, A. Schirone, S. Bravaccini, R. Maltoni, L. Cecconetto, S. Sarti, P. Serra, D. Amadori, A. Rocca
  • Medical Oncology, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.), 47014 - Meldola/IT

Abstract

Aim

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
<2cm 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.