Predictors of recovery of ovarian function during aromatase inhibitor therapy

Ann Oncol. 2013 Aug;24(8):2011-6. doi: 10.1093/annonc/mdt149. Epub 2013 Apr 23.

Abstract

Background: Aromatase inhibitors (AIs) may cause a rise in estrogen levels due to ovarian function recovery in women with clinical chemotherapy-induced ovarian failure (CIOF). We carried out a prospective registry trial to identify predictors of ovarian function recovery during AI therapy.

Patients and methods: Women with hormone receptor (HR)-positive breast cancer who remained amenorrheic and had hormonal levels consistent with ovarian failure after adjuvant chemotherapy were enrolled in a multi-institutional clinical trial of anastrozole. Subjects underwent frequent assessment using an ultrasensitive estradiol assay. Multivariable analysis was used to evaluate clinical and biochemical predictors of ovarian function recovery within 48 weeks.

Results: Recovery of ovarian function during AI therapy was observed in 13 of 45 (28.9%) assessable subjects after a median 2.1 months (range 0.6-11.9). Median age at chemotherapy initiation was statistically significantly different between those who regained ovarian function (43 years, range 40-51) and those who remained postmenopausal (49 years, range 44-52; P < 0.0001).

Conclusions: A significant proportion of women with CIOF recover ovarian function during AI therapy, including a woman over age 50 at initiation of chemotherapy. Tamoxifen remains the standard of care for women with CIOF. If an AI is used, patients should be monitored frequently with high-quality estradiol assays. CLINICALTRIALS.GOV: NCT00555477.

Keywords: aromatase inhibitor; breast cancer; chemotherapy-induced ovarian failure; estradiol; ovarian function.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amenorrhea
  • Anastrozole
  • Antineoplastic Agents, Alkylating / therapeutic use
  • Antineoplastic Agents, Hormonal / therapeutic use
  • Aromatase Inhibitors / adverse effects*
  • Aromatase Inhibitors / therapeutic use*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / surgery
  • Chemotherapy, Adjuvant
  • Cyclophosphamide / therapeutic use
  • Estradiol / blood*
  • Female
  • Humans
  • Middle Aged
  • Nitriles / therapeutic use
  • Ovary / drug effects*
  • Primary Ovarian Insufficiency / chemically induced*
  • Primary Ovarian Insufficiency / diagnosis
  • Prospective Studies
  • Receptors, Estrogen
  • Tamoxifen / therapeutic use
  • Triazoles / therapeutic use
  • Uterine Hemorrhage / chemically induced

Substances

  • Antineoplastic Agents, Alkylating
  • Antineoplastic Agents, Hormonal
  • Aromatase Inhibitors
  • Nitriles
  • Receptors, Estrogen
  • Triazoles
  • Tamoxifen
  • Anastrozole
  • Estradiol
  • Cyclophosphamide

Associated data

  • ClinicalTrials.gov/NCT00555477