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Breast Cancer Research and Treatment

, Volume 158, Issue 3, pp 553–561 | Cite as

A novel approach to breast cancer prevention: reducing excessive ovarian androgen production in elderly women

  • Giorgio Secreto
  • Sabina Sieri
  • Claudia Agnoli
  • Sara Grioni
  • Paola Muti
  • Barnett Zumoff
  • Milena Sant
  • Elisabetta Meneghini
  • Vittorio Krogh
Epidemiology

Abstract

Minimizing endogenous estrogen production and activity in women at high risk for breast cancer is a prominent approach to prevention of the disease. A number of clinical trials have shown that the administration of selective-estrogen receptor modulators or aromatase inhibitors significantly reduces the incidence of breast cancer in healthy women. Unfortunately, these drugs often produce adverse effects on the quality of life and are, therefore, poorly accepted by many women, even those who are at high risk for breast cancer. We propose a novel alternative approach to decreasing estrogen production: suppression of ovarian synthesis of the androgen precursors of estrogens by administration of long-acting gonadotropin-releasing hormone analogs to women with ovarian stromal hyperplasia. The specific target population would be elderly postmenopausal women, at increased risk of breast cancer, and with high blood levels of testosterone, marker of ovarian hyperandrogenemia, and recognized factor of risk for breast cancer. Testosterone levels are measured at baseline to identify women at risk and during the follow-up to evaluate the effectiveness of therapy. The postmenopausal ovary is an important source of excessive androgen production which originates from the ovarian interstitial cell hyperplasia frequently present in breast cancer patients. We propose to counter the source of androgen excess in women with ovarian stromal hyperplasia, thus reducing the substrate for estrogen formation without completely inhibiting estrogen synthesis. Available evidence indicates that gonadotropin-releasing hormone analogs can be safely used for breast cancer prevention in postmenopausal women.

Keywords

Breast cancer prevention Postmenopausal ovary Testosterone levels GnRH analogs Ovarian stromal hyperplasia 

Abbreviations

AR

Androgen receptors

BBD

Benign breast disease

DHEA

Dehydroepiandrosterone

DHEAS

Dehydroepiandrosterone-sulfate

EGF

Epidermal growth factor

EGFR

Epidermal growth factor receptor

HER2

Human epidermal growth factor receptor 2

ER

Estrogen receptor

FSH

Follicle stimulating hormone

GnRH

Gonadotropin-releasing hormone

LH

Luteinizing hormone

RIA

Radioimmunoassay

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Epidemiology and Prevention UnitFondazione IRCCS - Istituto Nazionale dei TumoriMilanItaly
  2. 2.Experimental Cancer Therapeutics, Department of OncologyMcMaster UniversityHamiltonCanada
  3. 3.Division of Endocrinology and MetabolismBeth Israel Medical CenterNew YorkUSA
  4. 4.Analytical Epidemiology and Health Impact UnitFondazione IRCCS, Istituto Nazionale dei TumoriMilanItaly

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