title: Complexities of androgen receptor signalling in breast cancer.
abstract: While the clinical benefit of androgen-based therapeutics in breast cancer has been known since the 1940s, we have only recently begun to fully understand the mechanisms of androgen action in breast cancer. Androgen signalling pathways can have either beneficial or deleterious effects in breast cancer depending on the breast cancer subtype and intracellular context. This review discusses our current knowledge of androgen signalling in breast cancer, including the relationship between serum androgens and breast cancer risk, the prognostic significance of androgen receptor (AR) expression in different breast cancer subtypes and the downstream molecular pathways mediating androgen action in breast cancer cells. Intracrine androgen metabolism has also been discussed and proposed as a potential mechanism that may explain some of the reported differences regarding dichotomous androgen actions in breast cancers. A better understanding of AR signalling in this disease is critical given the current resurgence in interest in utilising contemporary AR-directed therapies for breast cancer and the need for biomarkers that will accurately predict clinical response.
authors.affiliation: Department of PathologyTohoku University School of Medicine, Miyagi, Sendai, JapanDame Roma Mitchell Cancer Research LaboratoriesDiscipline of Medicine, The University of Adelaide and Hanson Institute, DX 650801, Adelaide, South Australia 5005, Australia.
authors.forename: Keely M
authors.initials: KM
authors.lastname: McNamara
authors.affiliation: Department of PathologyTohoku University School of Medicine, Miyagi, Sendai, JapanDame Roma Mitchell Cancer Research LaboratoriesDiscipline of Medicine, The University of Adelaide and Hanson Institute, DX 650801, Adelaide, South Australia 5005, Australia.
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Moore
authors.affiliation: Department of PathologyTohoku University School of Medicine, Miyagi, Sendai, JapanDame Roma Mitchell Cancer Research LaboratoriesDiscipline of Medicine, The University of Adelaide and Hanson Institute, DX 650801, Adelaide, South Australia 5005, Australia.
authors.forename: Theresa E
authors.initials: TE
authors.lastname: Hickey
authors.affiliation: Department of PathologyTohoku University School of Medicine, Miyagi, Sendai, JapanDame Roma Mitchell Cancer Research LaboratoriesDiscipline of Medicine, The University of Adelaide and Hanson Institute, DX 650801, Adelaide, South Australia 5005, Australia.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
authors.affiliation: Department of PathologyTohoku University School of Medicine, Miyagi, Sendai, JapanDame Roma Mitchell Cancer Research LaboratoriesDiscipline of Medicine, The University of Adelaide and Hanson Institute, DX 650801, Adelaide, South Australia 5005, Australia wayne.tilley@adelaide.edu.au.
authors.forename: Wayne D
authors.initials: WD
authors.lastname: Tilley
mesh_terms: D000728:Androgens / Q000494:pharmacology; D000818:Animals; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism* / Q000628:therapy; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D011379:Prognosis; D011944:Receptors, Androgen / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D064726:Triple Negative Breast Neoplasms / Q000235:genetics / Q000378:metabolism
chemical_list: C410798:AR protein, human; D000728:Androgens; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D011944:Receptors, Androgen
keywords: androgen; androgen regulated pathways; breast cancer; intracrinology; outcome; risk