Androgen excess in breast cancer development: Implications for prevention and treatment

Giorgio Secreto, Alessandro Girombelli, Vittorio Krogh

Research output: Contribution to journalReview article

2 Citations (Scopus)

Abstract

The aim of this review is to highlight the pivotal role of androgen excess in the development of breast cancer. Available evidence suggests that testosterone controls breast epithelial growth through a balanced interaction between its two active metabolites: cell proliferation is promoted by estradiol while it is inhibited by dihydrotestosterone. A chronic overproduction of testosterone (e.g. ovarian stromal hyperplasia) results in an increased estrogen production and cell proliferation that are no longer counterbalanced by dihydrotestosterone. This shift in the androgen/ estrogen balance partakes in the genesis of ER-positive tumors. The mammary gland is a modified apocrine gland, a fact rarely considered in breast carcinogenesis. When stimulated by androgens, apocrine cells synthesize epidermal growth factor (EGF) that triggers the ErbB family receptors. These include the EGF receptor and the human epithelial growth factor 2, both well known for stimulating cellular proliferation. As a result, an excessive production of androgens is capable of directly stimulating growth in apocrine and apocrine-like tumors, a subset of ER-negative/AR-positive tumors. The key role of androgen excess in the genesis of different subtypes of breast cancer has significant clinical implications for both treatment and prevention. Our belief stems from a thorough analysis of the literature, where an abundance of evidence is present to justify a clinical trial that would investigate the effectiveness of treating the underlying excessive androgen production.

Original languageEnglish
Pages (from-to)R81-R94
JournalEndocrine-Related Cancer
Volume26
Issue number2
DOIs
Publication statusPublished - Feb 2019

Fingerprint

Androgens
Breast Neoplasms
Dihydrotestosterone
Cell Proliferation
Testosterone
Estrogens
Breast
Apocrine Glands
Neoplasms
Human Mammary Glands
Growth
Epidermal Growth Factor Receptor
Epidermal Growth Factor
Hyperplasia
Estradiol
Intercellular Signaling Peptides and Proteins
Carcinogenesis
Clinical Trials

Keywords

  • Androgen
  • Androgen excess
  • Breast cancer
  • Dihydrotestosterone
  • ER-negative
  • ER-positive
  • Estradiol
  • Estrogen balance
  • Testosterone

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Oncology
  • Endocrinology
  • Cancer Research

Cite this

Androgen excess in breast cancer development : Implications for prevention and treatment. / Secreto, Giorgio; Girombelli, Alessandro; Krogh, Vittorio.

In: Endocrine-Related Cancer, Vol. 26, No. 2, 02.2019, p. R81-R94.

Research output: Contribution to journalReview article

Secreto, Giorgio ; Girombelli, Alessandro ; Krogh, Vittorio. / Androgen excess in breast cancer development : Implications for prevention and treatment. In: Endocrine-Related Cancer. 2019 ; Vol. 26, No. 2. pp. R81-R94.
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