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Background  We previously reported that tamoxifen (TAM)-induced ovarian hyperstimulation (OHS) is associated with high serum concentrations of estradiol in premenopausal women with breast cancer. To investigate risk factors for TAM-induced OHS, we performed a retrospective multicenter study.    Methods  Premenopausal patients who received surgical therapy for endocrine-dependent breast cancer ( n  = 235) were recruited in this study and classified into 4 groups: group A, treated with TAM alone; group B, TAM treatment after 2-year-combined therapy with a gonadotropin-releasing hormone (Gn-RH) agonist; group C, TAM treatment after chemotherapy; group D, 5-year-combined therapy with TAM and a Gn-RH agonist. A serum estradiol value of more than 300 pg/mL or mean follicular diameter of more than 30 mm was defined as OHS.    Results  The incidence of OHS in group A ( n  = 13/26, 50.0%) was significantly higher than those in group B ( n  = 17/63, 27.0%), group C ( n  = 20/110, 18.2%), and group D ( n  = 0/36, 0%). The incidence of OHS was significantly correlated with aging, and the median serum concentration of estradiol in the presence of OHS was 823.0 pg/mL. The incidence of OHS (less than 47 years old) was 62.5% in group A, 48.6% in group B, and 28.2% in group C, respectively. Notably, the incidence rate of OHS following amenorrhea in group C ( n  = 13/20, 65.0%) was significantly higher than that in group B ( n  = 1/17, 5.9%).    Conclusions  These findings indicate that the onset of OHS following amenorrhea was common in the post-chemotherapeutic group, while its ratio was low in the group after Gn-RH analog treatment, suggesting that combined treatment-based management involving TAM therapy is necessary for premenopausal patients with breast cancer.

bmc cancer

Ovarian hyperstimulation closely associated with resumption of follicular growth after chemotherapy during tamoxifen treatment in premenopausal women with breast cancer: a multicenter retrospective cohort study