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

Alberto Farolfi, Emanuela Scarpi, Andrea Rocca, Anita Mangia, Nicoletta Biglia, Lorenzo Gianni, Amelia Tienghi, Maria Rosaria Valerio, Giampietro Gasparini, Laura Amaducci, Marina Faedi, Editta Baldini, Alessandra Rubagotti, Roberta Maltoni, Angelo Paradiso, Dino Amadori

Research output: Contribution to journalArticlepeer-review


Aim To evaluate the optimal time interval from definitive surgery to commencing chemotherapy in early breast cancer (EBC). Patients and methods The relationship between time to initiation of adjuvant chemotherapy (TTC), calculated in weeks, and disease-free (DFS) or overall survival (OS), was assessed in 921 EBC patients with rapidly proliferating tumours (thymidine labelling index >3% or G3 or Ki67 >20%), randomised in a phase III clinical trial (NCT01031030) to receive chemotherapy with or without anthracyclines (epirubicin → cyclophosphamide, methotrexate and fluorouracil (CMF) versus CMF → epirubicin versus CMF). DFS, OS and 95% confidence intervals (95% confidence interval (CI)) were calculated by the Kaplan-Meier method. Multivariate Cox analysis was performed in relation with nodal involvement, oestrogen receptor and human epidermal growth factor receptor 2 (HER2) status, Ki67 value, type of adjuvant chemotherapy, menopausal status and tumour size. Results At a median follow-up of 105 months (range 2-188), a prolonged TTC resulted in a significant increase in the risk of relapse: hazard ratio (HR) 1.15 (95% CI 1.02-1.30, p = 0.019). Using a backward elimination procedure, TTC, tumour size and nodal involvement remained significantly associated with DFS. A time-dependent receiver-operating characteristic (ROC) curve analysis was subsequently utilised to evaluate the best cut-off for TTC, identifying 7 weeks as the best threshold for longer OS (p = 0.043): 8-year OS 88% (95% CI 85-90) for patients with a TTC

Original languageEnglish
Article number9535
Pages (from-to)1874-1881
Number of pages8
JournalEuropean Journal of Cancer
Issue number14
Publication statusPublished - Jul 1 2015


  • Adjuvant chemotherapy
  • Early breast cancer
  • Rapidly proliferating tumour
  • Time to initiation of adjuvant chemotherapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)


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