Incidence and prognostic impact of amenorrhea during adjuvant therapy in high-risk premenopausal breast cancer: analysis of a National Cancer Institute of Canada Clinical Trials Group Study--NCIC CTG MA.5.
OBJECTIVE
To investigate the therapeutic impact of chemotherapy-induced amenorrhea in premenopausal patients with breast cancer.


METHODS
We conducted a retrospective cohort study of a National Cancer Institute of Canada Clinical Trials Group phase III trial involving premenopausal patients randomized to receive cyclophosphamide, methotrexate, and fluorouracil (CMF), versus intensive cyclophosphamide, epirubicin, and fluorouracil (CEF). The objectives of our study were to describe the incidence of amenorrhea at 6 and 12 months post-random assignment and to determine the association of amenorrhea with relapse-free and overall survival.


RESULTS
Data on 442 patients were used in our analyses. Despite the higher cumulative dose of cyclophosphamide in the CMF treatment arm, at 6 months post-random assignment, the rate of amenorrhea was higher in the CEF group (relative risk, 1.2; 95% CI, 1.0 to 1.3), with no difference at 12 months. In the receptor-positive subgroup, 6-month amenorrhea rates were not associated with prognosis. In contrast, amenorrhea at 12 months was significantly associated with relapse-free survival (hazard ratio, 0.51; 95% CI, 0.32 to 0.82; P = .005) and overall survival (hazard ratio, 0.40; 95% CI, 0.22 to 0.72; P = .002).


CONCLUSIONS
Late chemotherapy-induced amenorrhea seems to be associated with improved outcome in patients with premenopausal, receptor-positive breast cancer.
Parulekar
Wendy R
WR
National Cancer Institute of Canada Clinical Trials Group, Queens University, 10 Stuart St, Kingston, Ontario K7L3N6, Canada. wparulekar@ctg.queensu.au
Day
Andrew G
AG
Ottaway
Jon A
JA
Shepherd
Lois E
LE
Trudeau
Maureen E
ME
Bramwell
Vivien
V
Levine
Mark
M
Pritchard
Kathleen I
KI
D000328:Adult; D000568:Amenorrhea / Q000150:complications / Q000453:epidemiology* / Q000209:etiology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D015994:Incidence; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D017697:Premenopause; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors
D015251:Epirubicin; D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate