Background:As per recent scenarios, drug resistance is a significant challenge in treating breast cancer for several reasons, such as genetic mutations, altered signaling pathways, and tumor microenvironment. Endocrine resistance is one of the biggest significant barriers to treatment, particularly in hormone receptor-positive (HR+) breast cancers, which depends on estrogen or progesterone signaling for growth. While therapies such as tamoxifen, aromatase inhibitors, and selective estrogen receptor degraders (SERDs) have effectively targeted these pathways, many patients develop resistance, rendering them less effective over time, which is driving a need for innovative therapeutics to treat breast cancer and overcome drug resistance and better treatment outcomes. Recent studies suggest that combining the different therapies, including immunotherapy, targeted therapy, chemotherapy, etc., with endocrine therapy, may bypass the endocrine resistance.Methodology: We conducted a comprehensive systematic review and meta-analysis examining the molecular mechanisms of endocrine resistance and evaluating randomized clinical trial outcomes, overall survival and progression-free survival in endocrine-resistant breast cancer patients treated with endocrine therapy, targeted therapy, immunotherapy, or chemotherapy.Results: We have analyzed 35 randomized clinical trial studies for different therapies along with combination therapy, and our results demonstrated that supplementary or additional therapies in endocrine resistance breast cancer patients have better progression-free and overall survival.Conclusions: The current study has demonstrated that combination therapies may have good survival results and patient outcomes in endocrine resistance. Also, This review sheds light on current challenges in drug resistance and the future direction of cancer treatment through a comprehensive analysis of these emerging treatment approaches to improve patient outcomes.
背景：根据近期情况，耐药性已成为乳腺癌治疗中的重大挑战，其原因包括基因突变、信号通路改变及肿瘤微环境等。内分泌耐药是治疗中最为显著的障碍之一，尤其对于依赖雌激素或孕激素信号促进生长的激素受体阳性乳腺癌。尽管他莫昔芬、芳香化酶抑制剂及选择性雌激素受体降解剂等疗法已有效靶向这些通路，但许多患者仍会产生耐药性，导致药物疗效随时间减弱，这推动了对创新疗法的需求，以治疗乳腺癌、克服耐药性并改善治疗效果。最新研究表明，将免疫疗法、靶向疗法、化疗等不同疗法与内分泌治疗相结合，可能规避内分泌耐药问题。 方法：我们进行了全面的系统性综述与荟萃分析，探讨内分泌耐药的分子机制，并评估了接受内分泌治疗、靶向治疗、免疫治疗或化疗的内分泌耐药乳腺癌患者的随机临床试验结果、总生存期及无进展生存期。 结果：我们分析了35项关于不同疗法及联合疗法的随机临床试验研究，结果显示，在内分泌耐药乳腺癌患者中，辅助或额外治疗能够带来更好的无进展生存期和总生存期。 结论：本研究证实，联合疗法在内分泌耐药治疗中可能获得良好的生存结果并改善患者预后。此外，本综述通过对这些新兴治疗方法的综合分析，揭示了当前耐药性面临的挑战以及未来癌症治疗的发展方向，以期为改善患者预后提供参考。
肿瘤(癌症)患者之家