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

  • Peyman Hadji
  • Annette Kauka
  • May Ziller
  • Katrin Birkholz
  • Monika Baier
  • Mathias Muth
  • Peter Kann
Clinical Trial

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

Adjuvant Endocrine therapy Hormone receptor-positive breast cancer Premenopausal Serum hormones Zoledronic 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)

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Peyman Hadji
    • 1
  • Annette Kauka
    • 1
  • May Ziller
    • 1
  • Katrin Birkholz
    • 2
  • Monika Baier
    • 3
  • Mathias Muth
    • 2
  • Peter Kann
    • 4
  1. 1.Department of Endocrinology, Reproductive Medicine and OsteoporosisPhilipps - University of MarburgMarburgGermany
  2. 2.BU OncologyNovartis Pharma GmbHNuernbergGermany
  3. 3.Clinical & Regulatory Affairs/Biometrics DepartmentNovartis Pharma GmbHNuernbergGermany
  4. 4.Department of Endocrinology and DiabetesPhilipps - University of MarburgMarburgGermany

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