Ovarian function in premenopausal women treated with adjuvant chemotherapy for breast cancer

Adjuvant chemotherapy for breast cancer causes significant changes in ovarian function. More young women survive breast cancer than ever before and they are at risk of the sequelae of early menopause. We attempted to (1) define menopausal status in the setting of adjuvant chemotherapy; (2) define chemotherapy-related amenorrhea (CRA); (3) document rates of permanent amenorrhea, temporary amenorrhea, and oligomenorrhea among different regimens; and (4) analyze variables that influence ovarian function.

We reviewed reports of the effects of adjuvant chemotherapy for breast cancer on ovarian function in premenopausal women. We searched Medline and Cancerlit from 1966 to 1995 on the following terms: breast neoplasms; chemotherapy, adjuvant; menstruation disorders; premature menopause, and amenorrhea. Further references were obtained from reports retrieved in the initial search.

A uniform definition of menopause and CRA is lacking. The wide range of CRA rates reported in adjuvant chemotherapy trials is a result, at least in part, of this problem. The average CRA rate reported in regimens based on cyclophosphamide, methotrexate, and fluorouracil (CMF) is 68% (95% confidence interval [CI], 66% to 70%), with a range of 20% to 100%. CRA incidence varies with age, cytotoxic agent, and cumulative dose.

Ovarian damage is the most significant long-term sequela of adjuvant chemotherapy in premenopausal breast cancer survivors. We suggest a common definition of the following important terms: menopausal status, CRA (early and late), temporary CRA, and oligomenorrhea in the setting of adjuvant treatment. With uniform definitions in place, regimens can be more precisely compared with respect to this important complication.