McNamara Keely M, Moore Nicole L, Hickey Theresa E, Sasano Hironobu, Tilley Wayne D
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.
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
Endocr Relat Cancer. 2014 Aug;21(4):T161-81. doi: 10.1530/ERC-14-0243. Epub 2014 Jun 20.
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.
自20世纪40年代以来，雄激素类疗法在乳腺癌治疗中的临床益处就已为人所知，但直到最近我们才开始全面了解雄激素在乳腺癌中的作用机制。根据乳腺癌亚型和细胞内环境的不同，雄激素信号通路在乳腺癌中可能产生有益或有害的影响。本文综述了我们目前对乳腺癌中雄激素信号的认识，包括血清雄激素与乳腺癌风险之间的关系、雄激素受体（AR）在不同乳腺癌亚型中的表达的预后意义，以及介导雄激素在乳腺癌细胞中作用的下游分子途径。文中还讨论了内分泌雄激素代谢，并将其作为一种潜在机制，用以解释报道的乳腺癌中雄激素二元作用的一些差异。鉴于当前对利用当代AR导向疗法治疗乳腺癌的兴趣再度兴起，以及对能够准确预测临床反应的生物标志物的需求，更好地了解这种疾病中的AR信号至关重要。
