Optimal duration of adjuvant chemotherapy for high-risk node-negative (N-) breast cancer patients: 6-year results of the prospective randomised multicentre phase III UNICANCER-PACS 05 trial (UCBG-0106)

Eur J Cancer. 2017 Jul:79:166-175. doi: 10.1016/j.ejca.2017.03.004. Epub 2017 May 11.

Abstract

Purpose: Optimal duration of adjuvant chemotherapy in the treatment of early-stage breast cancer remained to be investigated rigorously for the standard regimens in widespread use in North America (doxorubicin/cyclophosphamide, AC) and Europe (5-fluorouracil/epirubicin/cyclophosphamide, FEC). Whether six cycles of FEC 100 present an advantage, or not, compared with only four cycles was tested directly in a phase III prospective multicentre trial.

Patients and methods: Between 2002 and 2006, 1515 women between 18 and 65°years of age, with node negative N(-) high-risk early-stage breast cancer, were included in the study following breast surgery and axillary lymph node dissection or procedure by sentinel node technique. Inclusion in the study required tumour size T ≥ 1 cm and at least one of the high-risk factors: T > 2 cm, negative oestrogen receptor/progesterone receptor (ER- and PR-), Scarff-Bloom-Richardson (SBR) grade II or III and age ≤ 35°years. Patients were randomly assigned to either six FEC 100 (Arm A) or four FEC 100 (Arm B). The trial was powered to detect an absolute difference ≥6% in disease-free survival (DFS) at 5°years.

Results: At 6.1°years median follow-up, with 91 (12%) events recorded in Arm A versus 106 (14%) in Arm B, no statistically significant risk increase was associated with four versus six FEC 100: DFS (hazard ratio (HR) = 1.18; CI 95% [0.89-1.56], P = .24) and overall survival (OS) (HR = 1.39; CI 95% [0.91-2.13], P = .12).

Conclusion: Differences in chemotherapy duration did not induce notably different outcomes in our cohort of high-risk patients.

Clinical trial registry number: NCT00055679, Agence National de Sécurité du Médicament (ANSM) - France.

Keywords: Adjuvant chemotherapy; Breast cancer; Chemotherapy duration; FEC 100; High-risk patients; Node-negative.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Chemotherapy, Adjuvant / adverse effects
  • Chemotherapy, Adjuvant / methods
  • Chemotherapy, Adjuvant / mortality
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects
  • Epirubicin / administration & dosage
  • Epirubicin / adverse effects
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • France / epidemiology
  • Humans
  • Kaplan-Meier Estimate
  • Middle Aged
  • Prospective Studies
  • Receptor, ErbB-2 / metabolism
  • Risk Factors
  • Treatment Outcome
  • Tumor Burden
  • Young Adult

Substances

  • Epirubicin
  • Cyclophosphamide
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Fluorouracil

Supplementary concepts

  • FEC protocol

Associated data

  • ClinicalTrials.gov/NCT00055679
  • ClinicalTrials.gov/NCT00055679