Effect of adjuvant endocrine therapy on hormonal levels in premenopausal women with breast cancer: the ProBONE II study

Breast Cancer Res Treat. 2014 Apr;144(2):343-51. doi: 10.1007/s10549-014-2860-7. Epub 2014 Feb 12.

Abstract

Endocrine therapy (ET) is a key treatment modality in hormone receptor positive (HR+) early breast cancer (BC) patients. Although the anticancer activity of adjuvant ET + zoledronic acid (ZOL) has been investigated, the potential effects of ET ± ZOL on endocrine hormones in premenopausal women with HR+ early BC are not well understood. ProBONE II was prospective, double-blind, randomized controlled trial. Premenopausal patients with histologically confirmed invasive BC with no evidence of metastases and a T score >-2.5 received ET ± ZOL 4 mg every 3 months for 2 years. Serum levels of estradiol (E2), follicle-stimulating hormone, anti-muellerian hormone (AMH), inhibins A and B, sex hormone-binding globulin, parathyroid hormone, total testosterone, and vitamin D were evaluated at baseline and at every scheduled visit. Of 71 women enrolled, 70 were evaluable (n = 34, ZOL; n = 36, placebo). No statistically significant differences were observed in hormone levels, except E2 and AMH, which showed minor differences. These included decreases in serum E2 levels, which reached a nadir after 3 and 9 months in placebo and ZOL groups, respectively, and decrease in serum AMH levels throughout the study with ZOL, but remained constant with placebo after 6 months. Adverse events in ZOL-treated group were influenza-like illness (32.4 %), bone pain (32.4 %), chills (20.6 %), and nausea (23.5 %). ET ± ZOL was well tolerated. This study showed no influence of ZOL on hormonal level changes that accompany ET, supporting inclusion of ZOL in adjuvant therapy for premenopausal women with HR + BC.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / blood
  • Breast Neoplasms / blood*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Chemotherapy, Adjuvant / methods
  • Diphosphonates / administration & dosage
  • Diphosphonates / adverse effects
  • Double-Blind Method
  • Female
  • Goserelin / administration & dosage
  • Goserelin / adverse effects
  • Hormones / blood*
  • Humans
  • Imidazoles / administration & dosage
  • Imidazoles / adverse effects
  • Middle Aged
  • Premenopause / blood
  • Premenopause / drug effects*
  • Prospective Studies
  • Tamoxifen / administration & dosage
  • Tamoxifen / adverse effects
  • Young Adult
  • Zoledronic Acid

Substances

  • Biomarkers, Tumor
  • Diphosphonates
  • Hormones
  • Imidazoles
  • Tamoxifen
  • Goserelin
  • Zoledronic Acid