Amenorrhea in premenopausal women on the doxorubicin-and-cyclophosphamide-followed-by-docetaxel arm of NSABP B-30 trial

Abstract

The NSABP B-30 trial addresses whether amenorrhea after adjuvant chemotherapy increases survival. Preliminary to the trial outcome analysis, we examined the incidence of amenorrhea and its relationship to symptoms and quality of life (QOL) in the standard-care arm of this adjuvant breast cancer trial. Premenopausal women treated on the doxorubicin-and-cyclophosphamide-followed-by-docetaxel arm were included. Questionnaires assessing menstrual history, QOL, and symptoms were administered at baseline, day 1 of cycle 4 (or 9 weeks from start of chemotherapy for those who stopped chemotherapy early), and at 6, 12, and 24 months. Seven hundred and eight patients were evaluable for the analysis, with median potential follow-up of 57.5 months. Of these, 321 patients also participated in the QOL substudy. Of the 708 patients, 83% reported > or =1 episode of amenorrhea for > or =6 months. The estimated rate of resumption of menses at 24 months was 45.3% for women <40 years, 10.9% for women 40-50, and 3.2% for women >50 years. Those treated with tamoxifen were more likely to become amenorrheic (p = 0.003). Menstrual status was not significantly associated with QOL or symptoms. Prolonged amenorrhea is associated with a regimen that contains doxorubicin, cyclophosphamide, and docetaxel, and is age dependent and impacted by tamoxifen use. Vasomotor symptoms are common in this patient population but are not associated with menstrual status. These results can be used to inform premenopausal women about the risk and time course of amenorrhea associated with this common adjuvant therapy regimen, along with the effects on symptoms and QOL.

Figures

Fig. 1

Patients participating in the B-30 trial and those who took part in the current study. Of the 782 patients under the age of 61 who were assigned to AC → T and who received at least one cycle of chemotherapy, 708 (91%) had menstruated within 3 months at the start of treatment. (Fig. 1)

Fig. 2

Cumulative duration of amenorrhea (no menstrual bleeding for more than 1 month) by age in preliminary analysis subset of NSABP B-30 trial. 697 patients (11 patients removed due to inadequate data)