Chemotherapy-Related Amenorrhea and Quality of Life Among Premenopausal Women With Breast Cancer

IMPORTANCE Younger survivors of breast cancer frequently report more treatment-related symptoms, mostly related to the menopausal transition.

OBJECTIVE To assess factors associated with chemotherapy-related amenorrhea (CRA) and to evaluate its association with long-term quality of life (QOL).

The prospective, longitudinal Cancer Toxicities Study, a multicenter French cohort study, includes women with a diagnosis of stage I to III breast cancer and collects data approximately yearly after diagnosis. The current study reports outcomes up to 4 years after diagnosis for participants enrolled from 2012 to 2017. Participants included premenopausal women younger than 50 years treated with chemotherapy and not receiving adjuvant ovarian function suppression. Data analysis was performed from September 2021 to June 2023. EXPOSURES Clinical, socioeconomic, tumor, and treatment characteristics assessed at diagnosis (for the analysis of factors associated with CRA) and persistent CRA (for the QOL analysis).

The main outcome of interest was CRA at year 1 (Y1), year 2 (Y2), and year 4 (Y4) after diagnosis. Generalized estimating equations assessed associations of exposure variables with CRA. In the QOL analysis, QOL at Y4 (assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires C30 and BR23) was the outcome of interest. Multivariable random-effect mixed models assessed the association of persistent CRA (ie, never recovering menses after treatment) with QOL. RESULTS Among 1636 women, the mean (SD) age at diagnosis was 42.2 (5.6) years. Overall, 1242 of 1497 women (83.0%) reported CRA at Y1, 959 of 1323 women (72.5%) reported it at Y2, and 599 of 906 women (66.1%) reported it at Y4. Older age vs 18 to 34 years (adjusted odds ratio [OR] for 35 to 39 years, 1.84 [95% CI, 1.32 to 2.56]; adjusted OR for 40 to 44 years, 5.90 [95% CI, 4.23 to 8.24]; and adjusted OR for Ն45 years, 21.29 [95% CI, 14.34 to 31.61]) and receipt of adjuvant tamoxifen (adjusted OR, 1.97 [95% CI, 1.53 to 2.53]) were associated with higher likelihood of CRA. In the QOL analysis, 416 of 729 women (57.1%) had persistent CRA. However, late menses recovery among women aged 18 to 34 years with no menses at Y2 were reported by 11 of 21 women (52.4%) between Y2 and Y4. Persistent CRA was associated with worse insomnia (mean difference vs recovery at any time, 9.9 points [95% CI, 3.2 to 16.5 points]; P = .004), systemic therapy-related adverse effects (mean difference, 3.0 points [95% CI, 0.2 to 5.8 points]; P = .04), and sexual functioning (mean difference, -9.2 points [95% CI, -14.3 to -4.1 points]; P < .001) at Y4. (continued) Key Points Question Which factors are associated with chemotherapy-related amenorrhea, and what is its association with quality of life among breast cancer survivors? Findings In this cohort study of 1636 premenopausal women, 416 of 729 women (57.1%) included in the quality of life analysis reported persistent amenorrhea after chemotherapy, although late recovery patterns were observed. Amenorrhea was more frequent among older women and those receiving adjuvant tamoxifen and was significantly associated with worse insomnia, systemic therapy-related adverse effects, and sexual dysfunction. Meaning These findings can facilitate the treatment of premenopausal women with early breast cancer undergoing chemotherapy and experiencing chemotherapy-related amenorrhea, by informing risk communication, personalized counseling, and early supportive care referrals.