Ovarian Function Recovery During Anastrozole in Breast Cancer Patients With Chemotherapy-Induced Ovarian Function Failure

Irene E. G. van Hellemond, Ingeborg J. H. Vriens, Petronella G. M. Peer, Astrid C. P. Swinkels, Carolien H. Smorenburg, Caroline M. Seynaeve, Maurice J. C. van der Sangen, Judith R. Kroep, Hiltje de Graaf, Aafke H. Honkoop, Frans L. G. Erdkamp, Franchette W. P. J. van den Berkmortel, Jos J. E. M. Kitzen, Maaike de Boer, Wilfred K. de Roos, Sabine C. Linn, Alexander L. T. Imholz, Vivianne C. G. Tjan-Heijnen*, Dutch Breast Canc Res Grp BOOG

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Background: Aromatase inhibitors (AIs) are given as adjuvant therapy for hormone receptor-positive breast cancer in postmenopausal women, also to those with chemotherapy-induced ovarian function failure. The current analysis reports on endocrine data of patients with chemotherapy-induced ovarian function failure who were included in the phase III DATA study assessing different durations of adjuvant anastrozole after tamoxifen.

Methods: We identified all patients with chemotherapy-induced ovarian function failure. Women who underwent a bilateral ovariectomy or used luteinizing hormone-releasing hormone agonists before random assignment were excluded. Plasma estradiol and follicle-stimulating hormone levels were monitored until 30 months after random assignment at local laboratories. We aimed to determine the ovarian function recovery (OFR) rate during AI use by the cumulative incidence competing risk method and analyzed the trend of estradiol levels during AI use by a nested case-control approach in which a subset of control subjects were compared with the OFR patients excluding the value at OFR diagnosis.

Results: The 329 eligible patients had a median age of 50.0 years (range = 45-57 years) at random assignment. Thirty-nine patients developed OFR, corresponding with a 30-month recovery rate of 12.4%. Of these, 11 (28.2%) were age 50 years or older at AI initiation. The estradiol level decreased statistically significantly by 37.8% (95% CI = 27.4% to 46.7%) over the initial 30 months of AI treatment in both groups. However, the estradiol levels in the women who experienced OFR remained statistically significantly higher (difference = 20.6%, 95% CI = 2.0% to 42.7%) prior to OFR diagnosis compared with those who did not experience OFR.

Conclusions: The risk of OFR during AI treatment in breast cancer patients with chemotherapy-induced ovarian function failure is relevant, even beyond 45 years. Furthermore, women experiencing OFR had statistically significant higher estradiol levels during AI treatment (before OFR) than those without, with potential consequences regarding efficacy.

Original languageEnglish
Article number074
Number of pages9
JournalJournal of the National Cancer Institute
Issue number12
Publication statusPublished - Dec 2017



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