Breast Cancer Research and Treatment

, Volume 144, Issue 2, pp 343–351

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

Authors

    • Department of Endocrinology, Reproductive Medicine and OsteoporosisPhilipps - University of Marburg
  • Annette Kauka
    • Department of Endocrinology, Reproductive Medicine and OsteoporosisPhilipps - University of Marburg
  • May Ziller
    • Department of Endocrinology, Reproductive Medicine and OsteoporosisPhilipps - University of Marburg
  • Katrin Birkholz
    • BU OncologyNovartis Pharma GmbH
  • Monika Baier
    • Clinical & Regulatory Affairs/Biometrics DepartmentNovartis Pharma GmbH
  • Mathias Muth
    • BU OncologyNovartis Pharma GmbH
  • Peter Kann
    • Department of Endocrinology and DiabetesPhilipps - University of Marburg
Clinical Trial

DOI: 10.1007/s10549-014-2860-7

Cite this article as:
Hadji, P., Kauka, A., Ziller, M. et al. Breast Cancer Res Treat (2014) 144: 343. doi:10.1007/s10549-014-2860-7

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.

Keywords

AdjuvantEndocrine therapyHormone receptor-positive breast cancerPremenopausalSerum hormonesZoledronic acid

Abbreviations

AE

Adverse event

AI

Aromatase inhibitor

AMH

Anti-muellerian hormone

ANCOVA

Analysis of covariance

BMD

Bone mineral density

CI

Confidence interval

DFS

Disease-free survival

DXA

Dual energy X-ray absorptiometry

E2

Estradiol

ER

Estrogen receptor

ET

Endocrine therapy

FSH

Follicle-stimulating hormone

GnRH

Gonadotropin-releasing hormone

HR + BC

Hormone receptor-positive breast cancer

ITT

Intent-to-treat

IV

Intravenous

ONJ

Osteonecrosis of the jaw

OS

Overall survival

PTH

Parathyroid hormone

SAE

Serious adverse event

SD

Standard deviation

SHBG

Sex hormone-binding globulin

Supplementary material

10549_2014_2860_MOESM1_ESM.docx (28 kb)
Supplementary material 1 (DOCX 27 kb)

Copyright information

© Springer Science+Business Media New York 2014