Incidence And Prognostic Impact Of Amenorrhea During Adjuvant Therapy In High Risk Premenopausal Breast Cancer Patients: Analysis Of A National Cancer Institute Of Canada Clinical Trials Group (NCIC CTG) Phase III Study

Heather Jones, MD

University of Pennsylvania Cancer
Last Modified: May 15, 2001

Presenter: W. Parulekar
Affiliation: Kingston, ON, Canada


    One of the consequences of adjuvant therapy for breast cancer is drug-induced amenorrhea. The incidence and prognostic impact of drug induced amenorrhea (DIA) during adjuvant therapy with anthracycline containing regimens compared to standard CMF chemotherapy is poorly characterized. This study analyzed the database of a randomized Phase III NCIC CTG trial to further delineate both incidence and associated factors of DIA.

Materials and Methods:

  • Pre/perimenopausal patients (pts) with node positive breast cancer were allocated to receive: cyclophosphamide (C), methotrexate (M), fluorouracil (F)(CMF) or C, epirubicin (E) and F (CEF).
  • Treatment was given every 28 days for 6 cycles.
  • Of the 716 pts entered on the study, 541 fulfilled the inclusion criteria for this secondary retrospective analysis.
  • Patients must have had normal menstruation at randomization and received 6 cycles of chemotherapy.
  • DIA was defined as cessation of menses for > 3 months (mo) during treatment.
  • Complete menstrual data during treatment was found for 473 pts; 234(89%) pts treated with CEF and 239(86%) pts with CMF.


  • Median ages for both groups were similar.
  • Median follow-up for this analysis was 7.7yr.
  • The incidence of DIA was significantly higher in the CEF arm compared to CMF: 73.9 vs 61.9% (p=0.005).
  • DIA did not affect relapse free survival (RFS); 7 year RFS was (53% vs. 49%, p=0.3).
  • Adjustment for the variables of T stage, node status, age, receptor status and treatment using the stratified log rank test failed to demonstrate an effect on RFS (p=0.8).
  • No effect on overall survival (OS) was seen.

Authors' Conclusions

    The incidence of amenorrhea during treatment was significantly higher in the CEF arm compared to CMF and did not affect prognosis.

Clinical/Scientific Implications:

    This study attempts to answer the question is ovarian ablation a good thing for breast cancer patients. The study has the advantage of not having the possible confounding effects of tamoxifen in addition to the chemotherapy effects. One could argue that though the author's conclusion states that there is no benefit to ovarian ablation, the two-sided p value shows a trend towards improvement in RFS and OS. Two recent consensus panels have also sighted the benefits of ovarian ablation in breast cancer patients.

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