乳腺癌免疫治疗研究进展

doi:10.3760/cma.j.cn371439-20231017-00038

摘要/Abstract

摘要：

世界卫生组织国际癌症研究机构发布的2020年全球最新癌症负担数据显示，乳腺癌已经成为全世界范围内发病率最高的恶性肿瘤，在现有的化疗、靶向治疗及内分泌治疗等内科治疗手段的基础上，免疫治疗的发展为乳腺癌治疗提供了全新思路。目前，免疫治疗在不同分子分型、不同阶段乳腺癌中的临床研究均取得了一定的成果。此外，对免疫治疗与其他疗法联合应用、疗效预测标志物以及免疫相关不良反应的探索也在不断进行。乳腺癌免疫治疗领域未来的研究和发展仍存在很大的空间，这些研究进展将有助于推动免疫治疗在乳腺癌中的进一步应用。

关键词: 乳腺肿瘤, 免疫疗法, 免疫检查点抑制剂, 新辅助治疗

Abstract:

According to the latest global cancer burden data for 2020 released by the WHO's International Agency for Research on Cancer， breast cancer has become the malignant tumor with the highest incidence worldwide. Based on existing internal medicine treatment means like chemotherapy， targeted therapy and endocrine therapy， the development of immunotherapy provides novel solutions for the treatment of breast cancer. To date， the clinical research of immunotherapy in various molecular types and stages of breast cancer has reached certain achievements. In addition， the exploration of joint application with other therapies， predictive markers for efficacy， and immune-related adverse effects is also ongoing. The research and development in the field of breast cancer immunotherapy holds a promising prospect， and approaching research advances will promote the further application of immunotherapy in breast cancer.

Key words: Breast neoplasms, Immunotherapy, Immune checkpoint inhibitors, Neoadjuvant therapy

萨蔷, 徐航程, 王佳玉. 乳腺癌免疫治疗研究进展[J]. 国际肿瘤学杂志, 2024, 51(4): 227-234.

Sa Qiang, Xu Hangcheng, Wang Jiayu. Advances in immunotherapy for breast cancer[J]. Journal of International Oncology, 2024, 51(4): 227-234.

图/表 1

表1

乳腺癌治疗相关研究"

研究类别	期别	研究名称	研究对象（例数）	方案	结果	补充说明
HR阳性乳腺癌免疫治疗	Ⅱ	GIADA^[10]	HR阳性/HER2阴性乳腺癌（n=43）	3周期表柔比星+环磷酰胺，8周期依西美坦+纳武利尤单抗	pCR率：16.3%
	Ⅱ	I-SPY2^[11]	HR阳性/HER2阴性乳腺癌（n=136）	帕博利珠单抗（n=40）比紫杉醇标准化疗（n=96）	pCR率：30%比13%
	Ⅲ	KEYNOTE-756^[12] （NCT03725059）	ER阳性/HER2阴性乳腺癌	帕博利珠单抗+新辅助化疗+辅助内分泌治疗	进行中
	Ⅲ	CheckMate 7FL^[13] （NCT04109066）	ER阳性/HER2阴性乳腺癌	纳武利尤单抗+新辅助化疗+辅助内分泌治疗	进行中
双ICI联合治疗转移性乳腺癌	Ⅱ	Nimbus^[14]	高肿瘤突变负荷的HER2阴性转移性乳腺癌（n=30）	纳武利尤单抗+伊匹木单抗	ORR：13.3%
双ICI联合治疗转移性乳腺癌	Ⅱ	DART^[15]	HER2阴性转移性乳腺癌（n=17）	纳武利尤单抗+伊匹木单抗	中位PFS：2个月，ORR：18%，中位OS：12个月	包含TNBC 13例、ER/PR低表达+HER2阴性3例、ER/PR阳性+HER2 阴性1例
PARP抑制剂联合ICI治疗乳腺癌	Ⅰb/Ⅱ	TOPACIO/KEYNOTE-162^[16]	晚期或转移性TNBC（n=55，其中47例可评估疗效）	尼拉帕利+帕博利珠单抗	ORR：21%，DCR：49%，中位PFS：BRCA突变者8.3个月、BRCA野生型2.1个月
	Ⅰ/Ⅱ	MEDIOLA^[17]	种系BRCA突变的实体肿瘤（包含34例乳腺癌）	奥拉帕利+度伐利尤单抗	HR阳性亚组（n=13）对比TNBC亚组（n=17），中位PFS：9.9个月比4.9个月，ORR：69%比59%，中位OS：22.4个月比20.5个月	与OlympiAD研究中奥拉帕利单药治疗的PFS与缓解率相近^[18]
	Ⅱ	NCT02849496^[19]	非HER2阳性乳腺癌	奥拉帕利+阿替利珠单抗	进行中
	Ⅱ/Ⅲ	KEYLYNK-009（NCT04191135）^[20]	TNBC	奥拉帕利比化疗+帕博利珠单抗	进行中
TKI联合ICI治疗转移性TNBC	Ⅱ	COLET^[21]	转移性TNBC（n=106）	考比替尼+紫杉醇、考比替尼+阿替利珠单抗+紫杉醇、考比替尼+阿替利珠单抗+白蛋白紫杉醇	ORR：38.3%比34.4%比29.0%	阿替利珠单抗队列中，PD-L1阳性者的中位PFS与ORR存在改善趋势
TKI联合ICI治疗转移性TNBC	Ⅱ	LEAP-005^[22]	既往接受过1~2线治疗后进展的转移性TNBC（n=31）	仑伐替尼+帕博利珠单抗	ORR：29%

表1

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