美国乳腺癌内分泌靶向治疗指南更新
2016年，美国临床肿瘤学会首次发表激素受体阳性晚期乳腺癌内分泌治疗指南。5年以来，随着磷脂酰肌醇激酶PI3K抑制剂阿尔卑利昔的SOLAR-1研究、周期蛋白依赖性激酶CDK4/6抑制剂哌柏西利的PALOMA系列研究、瑞博西利的MONALEESA系列研究、阿贝西利的MONARCH研究、多腺苷二磷酸核糖聚合酶PARP抑制剂奥拉帕利的OlympiAD研究、他拉唑帕利的EMBRACA研究结果相继公布，美国临床肿瘤学会将该指南扩展至激素受体阳性HER2阴性晚期乳腺癌内分泌治疗和靶向治疗。
2021年7月29日，美国临床肿瘤学会《临床肿瘤学杂志》在线发表哈佛大学达纳法伯癌症研究所、美国临床肿瘤学会、密歇根大学护理学院、乳腺小叶癌研究倡导者、休斯顿卫理公会医院、国家癌症研究所、德克萨斯大学MD安德森癌症中心、哥伦布肿瘤医院、圣路易斯华盛顿大学医学院、爱荷华大学霍顿综合癌症中心、西雅图华盛顿大学、旧金山加利福尼亚大学综合癌症中心、英国萨塞克斯大学、皇家马斯登医院联合更新的激素受体阳性HER2阴性晚期乳腺癌内分泌治疗和靶向治疗指南。
指南专家组对2016年以来新发表的文献进行系统回顾，以确定可能改变临床实践的新数据。
结果，51篇文献符合入选标准并构成该指南的推荐意见证据基础。
该指南主要推荐意见更新如下：
对于激素受体阳性、HER2阴性、PIK3CA突变的晚期乳腺癌或既往内分泌治疗±CDK4/6抑制剂后发生转移的乳腺癌绝经女性患者以及男性患者，应提供阿尔卑利昔联合内分泌治疗（类型：循证；利大于弊；证据质量：高；推荐强度：中）
临床医生应对肿瘤组织或血浆细胞游离DNA进行二代测序以检测PIK3CA突变；如果细胞游离DNA未发现突变，那么应对肿瘤组织（如有）进行检测，因为这将检出少量额外的PIK3CA突变患者（类型：循证；利大于弊；证据质量：高；推荐强度：强）。
对于激素受体阳性HER2阴性晚期乳腺癌，目前缺乏足够数据推荐常规检测雌激素受体基因ESR1突变指导治疗；现有数据表明，与选择性雌激素受体降解剂氟维司群相比，芳香化酶抑制剂对循环肿瘤DNA或肿瘤ESR1突变患者疗效较低（类型：非正式共识；证据质量：低；推荐强度：中）
对于激素受体阳性HER2阴性晚期乳腺癌BRCA1或BRCA2突变携带者，内分泌治疗难以获益，奥拉帕利或他拉唑帕利应被用于一线至三线治疗（类型：循证；利大于弊；证据质量：中；推荐强度：强）
对于绝经后女性、绝经前女性（联合化疗抑制卵巢功能）、男性（联合促性腺激素释放激素类似物）激素受体阳性晚期乳腺癌患者，应提供非甾体芳香化酶抑制剂和CDK4/6抑制剂一线治疗（类型：基于证据，利大于弊；证据质量：高；推荐强度：强）
对于芳香化酶抑制剂治疗期间病变进展（或术后芳香化酶抑制剂辅助治疗1年内出现复发）患者，应提供氟维司群和CDK4/6抑制剂，无论转移病变是否经过一线化疗，或是作为一线治疗；治疗应限制于转移后未用过CDK4/6抑制剂的患者（类型：循证；利大于弊；证据质量：高；推荐强度：强）
相关链接
J Clin Oncol. 2021 Jul 29. Online ahead of print.
Endocrine Treatment and Targeted Therapy for Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer: ASCO Guideline Update.
Burstein HJ, Somerfield MR, Barton DL, Dorris A, Fallowfield LJ, Jain D, Johnston SRD, Korde LA, Litton JK, Macrae ER, Peterson LL, Vikas P, Yung RL, Rugo HS.
Dana Farber Cancer Institute, Boston, MA; American Society of Clinical Oncology, Alexandria, VA; University of Michigan School of Nursing, Ann Arbor, MI; Lobular Breast Cancer Research Advocate, San Francisco, CA; University of Sussex, Brighton, United Kingdom; Houston Methodist Hospital and Health Care, Houston, TX; Royal Marsden NHS Foundation Trust, London, United Kingdom; National Cancer Institute, Bethesda, MD; University of Texas MD Anderson Cancer Center, Houston, TX; Columbus Oncology Associates, Columbus, OH; Washington University School of Medicine, Saint Louis, MO; University of Iowa Holden Comprehensive Cancer Center, Iowa City, IA; University of Washington, Seattle, WA; University of California San Francisco Comprehensive Cancer Center, San Francisco, CA.
PURPOSE: To update recommendations of the ASCO systemic therapy for hormone receptor (HR)-positive metastatic breast cancer (MBC) guideline.
METHODS: An Expert Panel conducted a systematic review to identify new, potentially practice-changing data.
RESULTS: Fifty-one articles met eligibility criteria and form the evidentiary basis for the recommendations.
RECOMMENDATIONS: Alpelisib in combination with endocrine therapy (ET) should be offered to postmenopausal patients, and to male patients, with HR-positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CA-mutated, ABC, or MBC following prior endocrine therapy with or without a cyclin-dependent kinase (CDK) 4/6 inhibitor. Clinicians should use next-generation sequencing in tumor tissue or cell-free DNA in plasma to detect PIK3CA mutations. If no mutation is found in cell-free DNA, testing in tumor tissue, if available, should be used as this will detect a small number of additional patients with PIK3CA mutations. There are insufficient data at present to recommend routine testing for ESR1 mutations to guide therapy for HR-positive, HER2-negative MBC. For BRCA1 or BRCA2 mutation carriers with metastatic HER2-negative breast cancer, olaparib or talazoparib should be offered in the 1st-line through 3rd-line setting. A nonsteroidal aromatase inhibitor (AI) and a CDK4/6 inhibitor should be offered to postmenopausal women with treatment-naive HR-positive MBC. Fulvestrant and a CDK4/6 inhibitor should be offered to patients with progressive disease during treatment with AIs (or who develop a recurrence within 1 year of adjuvant AI therapy) with or without one line of prior chemotherapy for metastatic disease, or as first-line therapy. Treatment should be limited to those without prior exposure to CDK4/6 inhibitors in the metastatic setting.
PMID: 34324367
DOI: 10.1200/JCO.21.01392