title: A novel approach to breast cancer prevention: reducing excessive ovarian androgen production in elderly women.
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.
authors.affiliation: Epidemiology and Prevention Unit, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, Italy. giorgio.secreto@istitutotumori.mi.it.
authors.forename: Giorgio
authors.identifier: 0000-0001-9381-166X
authors.initials: G
authors.lastname: Secreto
authors.affiliation: Epidemiology and Prevention Unit, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Sabina
authors.initials: S
authors.lastname: Sieri
authors.affiliation: Epidemiology and Prevention Unit, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Agnoli
authors.affiliation: Epidemiology and Prevention Unit, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Grioni
authors.affiliation: Experimental Cancer Therapeutics, Department of Oncology, McMaster University, Hamilton, ON, Canada.
authors.forename: Paola
authors.initials: P
authors.lastname: Muti
authors.affiliation: Division of Endocrinology and Metabolism, Beth Israel Medical Center, New York, NY, USA.
authors.forename: Barnett
authors.initials: B
authors.lastname: Zumoff
authors.affiliation: Analytical Epidemiology and Health Impact Unit, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Milena
authors.initials: M
authors.lastname: Sant
authors.affiliation: Analytical Epidemiology and Health Impact Unit, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Meneghini
authors.affiliation: Epidemiology and Prevention Unit, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Krogh
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000378:metabolism / Q000517:prevention & control*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives*; D006801:Humans; D017588:Hyperandrogenism / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D010053:Ovary / Q000378:metabolism / Q000473:pathology; D017698:Postmenopause; D011788:Quality of Life; D013739:Testosterone / Q000378:metabolism*
chemical_list: D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone
keywords: Breast cancer prevention; GnRH analogs; Ovarian stromal hyperplasia; Postmenopausal ovary; Testosterone levels