Abstract
Young women with breast cancer experience unique treatment and survivorship issues centering on treatment-related amenorrhea (TRA), including fertility preservation and management of ovarian function as endocrine therapy. The Young Women’s Breast Cancer Study (YWS) is a multi-center, prospective cohort study of women diagnosed at age ≤40, enrolled from 2006 to 2016. Menstrual outcomes were self-reported on serial surveys. We evaluated factors associated with TRA using logistic regression. One year post-diagnosis, 286/789 (36.2%) experienced TRA, yet most resumed menses (2-year TRA: 120/699; 17.2%). Features associated with 1-year TRA included older age (OR≤30vs36-40 = 0.29 (0.17–0.48), OR31-35vs36-40 = 0.67 (0.46–0.94), p = 0.02); normal body mass index (BMI) (OR≥25vs18.5-24. =0.59 (0.41–0.83), p < 0.01); chemotherapy (ORchemo vs no chemo = 5.55 (3.60–8.82), p < 0.01); and tamoxifen (OR = 1.55 (1.11–2.16), p = 0.01). TRA rates were similar across most standard regimens (docetaxel/carboplatin/trastuzumab +/− pertuzumab: 55.6%; docetaxel/cyclophosphamide +/− trastuzumab/pertuzumab: 41.8%; doxorubicin/cyclophosphamide/paclitaxel +/− trastuzumab/pertuzumab: 44.1%; but numerically lower with AC alone (25%) or paclitaxel/trastuzumab (11.1%). Among young women with breast cancer, lower BMI appears to be an independent predictor of TRA. This finding has important implications for interpretation of prior studies, future research, and patient care in our increasingly obese population. Additionally, these data describe TRA associated with use of docetaxel/cyclophosphamide, which is increasingly being used in lieu of anthracycline-containing regimens. Collectively, these data can be used to inform use of fertility preservation strategies for women who need to undergo treatment as well as the potential need for ovarian suppression following modern chemotherapy for young women with estrogen-receptor-positive breast cancer.Clinical trial registration: www.clinicaltrials.gov, NCT01468246.
Highlights
Young women with breast cancer, defined as those diagnosed at age ≤40 years, represent a small minority of breast cancer patients overall[1]
To what extent this risk stems from the biology of premenopausal breast cancer versus suboptimal endocrine therapy remains poorly understood
To acknowledge that some women experience bleeding in the first few months after initiating treatment before ovarian function is impacted, we evaluated treatment-related amenorrhea (TRA) at 1 year as the proportion with no period within 6 months prior (286/789; 36.2%) and at 2
Summary
Young women with breast cancer, defined as those diagnosed at age ≤40 years, represent a small minority of breast cancer patients overall[1]. Young age has historically been considered a risk factor for disease recurrence[3,4] and recent data have demonstrated that this risk appears to be predominantly among those with luminal A and luminal B breast cancer subtypes[5]. To what extent this risk stems from the biology of premenopausal breast cancer versus suboptimal endocrine therapy remains poorly understood. Ovarian function suppression (OFS) is a well-recognized therapeutic strategy for premenopausal women with hormone-receptor-positive (HR+) breast cancer and those who experience chemotherapy-associated amenorrhea experience improved risk of recurrence[6,7]. Chemotherapy-related amenorrhea and OFS may have many negative impacts, including infertility or subfertility, vasomotor symptoms, impaired sexual functioning, and long-term medical sequelae including bone loss[9]
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