Menstrual history and quality-of-life outcomes in women with node-positive breast cancer treated with adjuvant therapy on the NSABP B-30 trial

Abstract

Purpose: Premenopausal women with breast cancer receiving adjuvant chemotherapy are at risk for amenorrhea. The National Surgical Adjuvant Breast and Bowel Project B-30 trial included menstrual history (MH) and quality-of-life (QOL) studies to compare treatments on these outcomes.

Patients and methods: Patients were randomly assigned to sequential doxorubicin (A) and cyclophosphamide (C) followed by docetaxel (T; AC→T), concurrent TAC, or AT, which varied in duration (24, 12, 12 weeks, respectively), and use of C. Endocrine therapy was prescribed for women with hormone receptor-positive tumors. MH and QOL were assessed with standardized questionnaires at baseline; cycle 4, day 1; and every 6 months through 24 months. Prespecified analyses examined rates of amenorrhea by treatment arm, the relationship between amenorrhea and QOL, and QOL by treatment arm.

Results: Amenorrhea 12 months after random assignment was significantly different between treatment groups: 69.8% for AC→T, 57.7% for TAC, and 37.9% for AT (P < .001). The AT group without tamoxifen had the lowest rate of amenorrhea. QOL was poorer for patients receiving AC→T at 6 months but similar to others by 12 months. Post-treatment symptoms were increased above baseline for all treatments. Multivariable repeated measures modeling demonstrated that treatment arm, time point, age, and tamoxifen use were significantly associated with symptom severity (all P values < .002).

Conclusion: Amenorrhea rates differed significantly by treatment arm, with the AT arm having the lowest rate. Patients treated with longer duration therapy (AC→T) had greater symptom severity and poorer QOL at 6 months, but did not differ from shorter duration treatments at 12 months.

Fig 1.

(A) Flow diagram showing recruitment and participation of women from National Surgical Adjuvant Breast and Bowel Project (NSABP) B-30 in the menstrual history (MH) substudy. (B) Flow diagram showing recruitment and participation of women from NSABP B-30 into the quality-of-life (QOL) and symptoms substudy. A, doxorubicin; C, cyclophosphamide; T, docetaxel.

Fig 2.

Rate of prolonged amenorrhea at each time point for chemotherapy and tamoxifen intention-to-treat groups. Excludes those who experienced amenorrhea for 3 months at baseline and those with a hysterectomy/oophorectomy or unknown status at each time point. A, doxorubicin; C, cyclophosphamide; T, docetaxel; tam, tamoxifen.

Fig 3.

(A) Duration of amenorrhea in months according to age group. (B) Duration of amenorrhea in months by treatment group among those ≤ age 40 years. (C) Duration of amenorrhea in months by treatment group among those older than age 40 years. A, doxorubicin; C, cyclophosphamide; T, docetaxel.

Fig 4.

(A) Functional Assessment of Chronic Illness Therapy–B trial outcome index (TOI) by treatment group and time point. (B) Symptom severity by treatment group and time point. SCLSUM, symptom checklist summary score; Pre-R_x, pretreatment; C4D1, cycle 4, day 1; A, doxorubicin; C, cyclophosphamide; T, docetaxel.