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免疫疗法是乳腺癌治疗的热点之一，目前超过290项有关乳腺癌免疫疗法的临床研究正在进行。 2019年4月11日，《美国医学会杂志》肿瘤学分册在线发表纽约大学医学院珀尔马特癌症中心、国家癌症研究所、哥伦比亚大学医学中心、美国食品药品管理局、弗吉尼亚联邦大学梅西癌症中心、洛杉矶加利福尼亚大学西达赛奈医疗中心、哈佛大学达纳法伯癌症研究所、布列根医院和波士顿妇女医院、波特兰大学普罗维登斯癌症研究所、北卡罗来纳大学教堂山分校莱恩伯格综合癌症中心、德克萨斯大学MD安德森癌症中心、俄亥俄州立大学综合癌症中心、纽约爱因斯坦医学院蒙蒂菲奥里癌症中心、华盛顿大学弗雷德哈钦森癌症研究中心、《美国医学会杂志》肿瘤学分册编辑部的乳腺癌免疫疗法现状概览，突显了免疫疗法对于早期和转移性乳腺癌的潜力。 作者于2018年4月24日和2018年6月30日分别对美国国家卫生研究院临床研究登记网站ClinicalTrials.gov和PubMed数据库进行检索，确定乳腺癌免疫疗法研究，发现免疫检查点阻断是乳腺癌研究最多的免疫疗法形式。免疫检查点阻断剂单药治疗乳腺癌患者已经获得客观缓解，尤其早期治疗的客观缓解率更高。对于缓解患者，这些缓解时间持久。最新数据表明，免疫检查点阻断联合化疗可以提高临床效果。现行研究正在评估将免疫检查点阻断剂与其他化疗药物、靶向疗法、疫苗、局部切除疗法联合以增强缓解的策略。截至目前，尚未确定预测免疫检查点阻断缓解的可靠生物标志。 因此，联合治疗方法对于肿瘤、微环境与宿主因素的了解比较深入，有助于联合治疗决策，预计将成为乳腺癌免疫疗法的进一步研究方向。包含合理终点的严谨研究设计及其相关研究，对于确定增强乳腺肿瘤免疫应答的最佳策略至关重要。 JAMA Oncol. 2019 Apr 11. [Epub ahead of print] Current Landscape of Immunotherapy in Breast Cancer: A Review. Sylvia Adams, Margaret E. Gatti-Mays, Kevin Kalinsky, Larissa A. Korde, Elad Sharon, Laleh Amiri-Kordestani, Harry Bear, Heather L. McArthur, Elizabeth Frank, Jane Perlmutter, David B. Page, Benjamin Vincent, Jennifer F. Hayes, James L. Gulley, Jennifer K. Litton, Gabriel N. Hortobagyi, Stephen Chia, Ian Krop, Julia White, Joseph Sparano, Mary L. Disis, Elizabeth A. Mittendorf. Perlmutter Cancer Center, NYU School of Medicine, New York, New York; National Cancer Institute, Bethesda, Maryland; Columbia University Medical Center, New York, New York; National Cancer Institute, Rockville, Maryland; US Food and Drug Administration, Silver Spring, Maryland; Virginia Commonwealth University, Massey Cancer Center, Richmond; Cedars-Sinai Medical Center, Los Angeles, California; Dana-Farber Cancer Institute, Boston, Massachusetts; Gemini Group, Ann Arbor, Michigan; Providence Cancer Institute, Earle A. Chiles Research Institute, Portland, Oregon; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill; MD Anderson Cancer Center, Houston, Texas; British Columbia Cancer Agency, Vancouver, British Columbia, Canada; The Ohio State University Comprehensive Cancer Center, Columbus; Montefiore Einstein Center for Cancer Care, New York, New York; Fred Hutchinson Cancer Research Center, Seattle, Washington; Editor, JAMA Oncology; Brigham and Women's Hospital, Boston, Massachusetts; Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts. This narrative review describes the current landscape of immunotherapy in breast cancer. IMPORTANCE: There is tremendous interest in using immunotherapy to treat breast cancer, as evidenced by the more than 290 clinical trials ongoing at the time of this narrative review. The objective of this review is to describe the current status of immunotherapy in breast cancer, highlighting its potential in both early-stage and metastatic disease. OBSERVATIONS: After searching ClinicalTrials.gov on April 24, 2018, and PubMed up to June 30, 2018, to identify breast cancer immunotherapy trials, we found that immune checkpoint blockade (ICB) is the most investigated form of immunotherapy in breast cancer. Use of ICB as monotherapy has achieved objective responses in patients with breast cancer, with higher rates seen when administered in earlier lines of therapy. For responding patients, those responses are durable. More recent data suggest clinical efficacy when ICB is given in combination with chemotherapy. Ongoing studies are evaluating combination strategies pairing ICB with additional chemotherapeutic agents, targeted therapy, vaccines, and local ablative therapies to enhance response. To date, robust predictive biomarkers for response to ICB have not been established. CONCLUSIONS AND RELEVANCE: It is anticipated that combination therapy strategies will be the way forward for immunotherapy in breast cancer, with an improved understanding of tumor, microenvironment, and host factors informing treatment combination decisions. Thoughtful study design incorporating appropriate end points and correlative studies will be critical in identifying optimal strategies for enhancing the immune response against breast tumors. DOI: 10.1001/jamaoncol.2018.7147
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