Androgen receptor and antiandrogen therapy in male breast cancer.
Cancers arising in the male breast are uncommon. Male breast cancer is a hormone-driven disease that often expresses the estrogen receptor, and antiestrogen therapy represents the mainstay of treatment. Paradoxically, the advent of a wave of antiestrogens eclipsed the therapeutic potential of alternative therapeutic options. At the beginning of the hormonal therapy era the administration of antiandrogens to metastatic male breast cancer patients was proposed. Ever since the use of these compounds has largely been neglected. A therapeutic role for antiandrogens has been envisioned again in recent years. First, molecular characterization efforts pointed to the androgen receptor as a potential therapeutic target. Second, the development of aromatase inhibitors unexpectedly raised the need for neutralizing androgens in order to tackle endocrine feedback mechanisms responsible for acquired resistance. We herein provide an overview of molecular studies where the androgen receptor was investigated at the genomic, transcriptomic or phenotypic level. We then discuss androgens in the context of the endocrine networks nourishing male breast cancer. Finally, clinical evidence on antiandrogens is summarized along with strategies should be implemented to improve the medical management of these patients.
Division of Medical Oncology B, "Regina Elena" National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy.
Luigi
L
Di Lauro
Division of Medical Oncology B, "Regina Elena" National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy; Scientific Direction, "Regina Elena" National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy.
Maddalena
M
Barba
Division of Medical Oncology B, "Regina Elena" National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy.
Laura
L
Pizzuti
Division of Medical Oncology B, "Regina Elena" National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy.
Patrizia
P
Vici
Division of Medical Oncology B, "Regina Elena" National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy.
Domenico
D
Sergi
Department of Pathology, "Regina Elena" National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy.
Anna
A
Di Benedetto
Department of Pathology, "Regina Elena" National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy.
Marcella
M
Mottolese
Leeds Institute of Cancer and Pathology, Wellcome Trust Brenner Building, University of Leeds, LS9 7TF Leeds, UK.
Valerie
V
Speirs
Department of Medical Oncology, Campus Bio-Medico University of Rome, 00128 Rome, Italy.
Daniele
D
Santini
Scientific Direction, "Regina Elena" National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy.
Ruggero
R
De Maria
Division of Medical Oncology B, "Regina Elena" National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy; Scientific Direction, "Regina Elena" National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy. Electronic address: maugeri@ifo.it.
Marcello
M
Maugeri-Saccà
D000726:Androgen Antagonists / Q000627:therapeutic use*; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D018567:Breast Neoplasms, Male / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D058990:Molecular Targeted Therapy; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011944:Receptors, Androgen / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome
C410798:AR protein, human; D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D011944:Receptors, Androgen
Androgen receptor; Androgens; Anti-androgen therapy; Gonadotropin-releasing hormone analogs; Male breast cancer