Laboratory of Molecular Endocrinology and Oncology, CHUL (CHUQ) Research Center and Laval University, 2705 Boulevard Laurier, QC G1V 4G2, Canada.
Nat Rev Endocrinol. 2010 Sep;6(9):485-93. doi: 10.1038/nrendo.2010.92. Epub 2010 Jul 20.
Breast cancer is a major cause of death in Western women, with a 10% lifetime risk of the disease. Most breast cancers are estrogen-dependent. Molecular therapies for breast cancer have developed rapidly in the past few decades and future treatment strategies are being investigated. The selective estrogen receptor (ER) modulator tamoxifen, which until now has served as a standard therapy, functions not only as an estrogen antagonist but also as an estrogen agonist in terms of bone maintenance. Aromatase inhibitors have performed well in international trials and have become a new standard therapy for estrogen-dependent breast cancer. The systematic study of estrogen activation pathways suggests that the enzymes steroid sulfatase and 17beta-hydroxysteroid dehydrogenase type 1, which both have pivotal roles in estrogen biosynthesis, are promising targets; the results of a phase I trial of steroid sulfatase inhibitors are encouraging. The activity of the human epidermal growth factor receptor (HER) pathway correlates negatively with that of the ER. HER2 is overexpressed in 22% of all breast cancers. In the decade since HER2 began being targeted, the monoclonal antibody trastuzumab has been used as well as pertuzumab and HER2 vaccines. Among the estrogen-independent breast cancers, the basal-like subtype has low survival, and therapeutic improvement is a priority. Crosstalk between ER and HER2 signaling pathways means that combinatory therapies may hold the key to enhancement of treatment responses. Other molecular therapies involving functional genomics and RNA interference studies also hold promise.
乳腺癌是西方女性的主要死亡原因，其终生患病风险为 10%。大多数乳腺癌依赖于雌激素。在过去几十年中，乳腺癌的分子治疗迅速发展，未来的治疗策略正在研究中。选择性雌激素受体（ER）调节剂他莫昔芬，直到现在一直是一种标准治疗方法，它不仅作为雌激素拮抗剂，而且在骨维持方面也作为雌激素激动剂发挥作用。芳香酶抑制剂在国际试验中表现良好，已成为雌激素依赖性乳腺癌的新的标准治疗方法。雌激素激活途径的系统研究表明，在雌激素生物合成中具有关键作用的甾体硫酸酯酶和 17β-羟甾脱氢酶 1 型酶是有前途的靶标；甾体硫酸酯酶抑制剂的 I 期试验结果令人鼓舞。人类表皮生长因子受体（HER）途径的活性与 ER 的活性呈负相关。HER2 在所有乳腺癌中的 22%过度表达。在针对 HER2 开始的十年中，已经使用了曲妥珠单抗、帕妥珠单抗和 HER2 疫苗等单克隆抗体。在非雌激素依赖性乳腺癌中，基底样亚型的生存率较低，因此优先考虑治疗改善。ER 和 HER2 信号通路的串扰意味着联合治疗可能是增强治疗反应的关键。涉及功能基因组学和 RNA 干扰研究的其他分子治疗也有希望。
