Dipartimento di Endocrinologia ed Oncologia Molecolare e Clinica, Università di Napoli Federico II, Napoli, Italy.
Oncology. 2009;77 Suppl 1:23-37. doi: 10.1159/000258493. Epub 2010 Feb 2.
Endocrine therapy, the first targeted therapy in oncology, is the most successful systemic therapy in the management of estrogen receptor (ER)-positive breast cancer. Approximately 50% of patients with advanced disease do not respond to first-line treatment with tamoxifen, and many women who receive tamoxifen as adjuvant therapy experience tumor relapse and die from their disease. Aromatase inhibitors are proving superior to tamoxifen, at least in certain patient subsets. However, the response rate to these compounds is only slightly higher than that to tamoxifen in patients with advanced breast cancer, and both de novo or acquired resistance also occur, limiting the efficacy of the treatment. Advanced studies of ER biology have highlighted the role of an intimate cross talk between the ER and HER2/growth factor signaling pathways as a fundamental contributor to the development of resistance to hormone therapies. The aim of this review article is to summarize the current knowledge on mechanisms of resistance of breast cancer cells to endocrine therapies due to the cross talk between the ER and growth factor signaling pathways, and to explore newly available therapeutic strategies that could prolong duration of response and circumvent endocrine-resistant tumor growth.
内分泌治疗是肿瘤学中的第一种靶向治疗方法,是治疗雌激素受体(ER)阳性乳腺癌最成功的全身治疗方法。大约 50%的晚期疾病患者对一线他莫昔芬治疗无反应,许多接受他莫昔芬作为辅助治疗的女性会出现肿瘤复发并死于疾病。芳香酶抑制剂被证明优于他莫昔芬,至少在某些患者亚组中如此。然而,这些化合物在晚期乳腺癌患者中的反应率仅略高于他莫昔芬,并且也会出现新出现或获得性耐药,限制了治疗的疗效。对 ER 生物学的深入研究强调了 ER 和 HER2/生长因子信号通路之间的密切相互作用在激素治疗耐药性发展中的作用。本文综述了由于 ER 和生长因子信号通路之间的相互作用导致乳腺癌细胞对内分泌治疗产生耐药性的机制的最新知识,并探讨了新的治疗策略,这些策略可以延长反应时间并规避内分泌耐药性肿瘤的生长。