Dose-dense adjuvant chemotherapy in premenopausal breast cancer patients: A pooled analysis of the MIG1 and GIM2 phase III studies

M. Lambertini, M. Ceppi, F. Cognetti, G. Cavazzini, M. De Laurentiis, S. De Placido, A. Michelotti, G. Bisagni, A. Durando, E. Valle, T. Scotto, A. De Censi, A. Turletti, M. Benasso, S. Barni, F. Montemurro, F. Puglisi, A. Levaggi, S. Giraudi, C. BighinP. Bruzzi, L. Del Mastro, MIG González-Siso, GIM study groups

Research output: Contribution to journalArticlepeer-review


BACKGROUND: No evidence exists to recommend a specific chemotherapy regimen in young breast cancer patients. We performed a pooled analysis of two randomised clinical trials to evaluate the efficacy of adjuvant dose-dense chemotherapy in premenopausal breast cancer patients and its impact on the risk of treatment-induced amenorrhoea. PATIENTS AND METHODS: In the MIG1 study, node-positive or high-risk node-negative patients were randomised to 6 cycles of fluorouracil/epirubicin/cyclophosphamide every 2 (dose-dense) or 3 (standard-interval) weeks. In the GIM2 study, node-positive patients were randomised to 4 cycles of dose-dense or standard-interval EC or FEC followed by 4 cycles of dose-dense or standard-interval paclitaxel. Using individual patient data, the hazard ratio (HR) for overall survival by means of a Cox proportional hazards model and the odds ratio for treatment-induced amenorrhoea through a logistic regression model were calculated for each study. A meta-analysis of the two studies was performed using the random effect model to compute the parameter estimates. RESULTS: A total of 1,549 patients were included. Dose-dense chemotherapy was associated with a significant improved overall survival as compared to standard-interval chemotherapy (HR, 0.71; 95% confidence intervals [CI], 0.54-0.95; p = 0.021). The pooled HRs were 0.78 (95% CI, 0.54-1.12) and 0.65 (95% CI, 0.40-1.06) for patients with hormone receptor-positive and -negative tumours, respectively (interaction p = 0.330). No increased risk of treatment-induced amenorrhoea was observed with dose-dense chemotherapy (odds ratio, 1.00; 95% CI, 0.80-1.25; p = 0.989). CONCLUSION: Dose-dense adjuvant chemotherapy may be considered the preferred treatment option in high-risk premenopausal breast cancer patients.
Original languageEnglish
Pages (from-to)34-42
Number of pages9
JournalEuropean Journal of Cancer
Publication statusPublished - Jan 1 2017


  • Adult
  • Amenorrhea/chemically induced
  • Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use
  • Breast Neoplasms/drug therapy
  • Chemotherapy, Adjuvant
  • Cyclophosphamide/adverse effects/therapeutic use
  • Dose-Response Relationship, Drug
  • Epirubicin/adverse effects/therapeutic use
  • Female
  • Fluorouracil/adverse effects/therapeutic use
  • Humans
  • Middle Aged
  • Premenopause
  • Survival Analysis
  • Breast cancer
  • Dose-dense chemotherapy
  • Premenopausal patients
  • Treatment-induced amenorrhoea


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