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Five-year changes in ovarian function restoration in premenopausal patients with breast cancer taking tamoxifen after chemotherapy: An ASTRRA study report

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Kim, Hee J.; Noh, Woo C.; Nam, Seok J.; Park, Byeong-Woo; Lee, Eun S.; Im, Seock A.; Jung, Yong S.; Yoon, Jung H.; Kang, Sung S.; Park, Kyong H.; Lee, Soo-Jung; Jeong, Joon; Lee, Min H.; Cho, Se H.; Kim, Sung Y.; Kim, Hyun-Ah; Han, Se-Hwan; Han, Wonshik; Hur, Min H.; Kim, Seonok; Ahn, Sei H.

Issue Date
Pergamon Press Ltd.
European Journal of Cancer, Vol.151, pp.190-200
Background: Adding ovarian function suppression (OFS) after chemotherapy improves survival in young women with moderate-and high-risk breast cancer. Assessment of ovarian function restoration after chemotherapy becomes critical for subsequent endocrine treatment and addressing fertility issues. Patients and methods: In the adding OFS after chemotherapy trial, patients who resumed ovarian function up to 2 years after chemotherapy were randomised to receive either 5 years of tamoxifen or adding 2 years of OFS with tamoxifen. Ovarian function was evaluated from enrolment to randomisation, and patients who did not randomise because of amenorrhoea for 2 years received tamoxifen and were followed up for 5 years. Prospectively collected consecutive hormone levels (proportion of patients with premenopausal follicle-stimulating hormone [FSH] levels <30 mIU/mL and oestradiol [E2] levels >40 pg/mL) and history of menstruation were available for 1067 patients with breast cancer. Results: Over 5 years of tamoxifen treatment, 69% of patients resumed menstruation and 98% and 74% of patients satisfied predefined ovarian function restoration as per serum FSH and E2 levels, respectively. Menstruation was restored in 91% of patients younger than 35 years at baseline, but in only 33% of 45-year-old patients over 5 years. Among these patients, 41% experienced menstruation restoration within 2 years after chemotherapy and 28% slowly restored menstruation after 2-5 years. Younger age (<35 years) at baseline, anthracycline without taxanes and <90 days of chemotherapy were predictors of menstruation restoration. Conclusions: During 5 years of tamoxifen treatment after chemotherapy, two-thirds of the patients experienced menstruation restoration, especially patients younger than 35 years. Young age, Adriamycin without taxanes and short duration of chemotherapy appeared to have a positive effect on ovarian reserves in the long term. Trial registration: identifier: NCT00912548. (c) 2021 Elsevier Ltd. All rights reserved.
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  • Department of Medicine
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