三阴性乳腺癌免疫微环境预后意义
众所周知，肿瘤免疫微环境对患者预后和免疫治疗效果具有显著影响。2019年，美国癌症研究协会《临床癌症研究》发表复旦大学附属肿瘤医院江一舟、余科达、邵志敏等学者的研究报告，根据生物信息学的免疫基因组学分析，将三阴性乳腺癌的微环境分为三种类型：免疫沙漠型、先天免疫失活型、免疫炎症型。免疫炎症型被认为是“免疫热情型肿瘤”，免疫治疗可能有效，而另外两个被认为是“免疫冷淡型肿瘤”，免疫治疗效果不佳，需要其他对策。那么，三阴性乳腺癌免疫微环境特征对化疗效果和患者生存的影响如何？
2021年9月21日，瑞士《分子生物科学前沿》在线发表复旦大学附属肿瘤医院朱思远、马丁、叶富贵、邵志敏、余科达等学者的PATTERN研究生物标志物分析报告，探讨了免疫微环境表现型对三阴性乳腺癌化疗效果和患者生存的影响。
PATTERN (NCT01216111): Adjuvant Platinum and Taxane in Triple-negative Breast Cancer (A Prospective, Randomized, Open-label, Multicentric, phase III Clinical Trial Compared With PC and CEF100 Followed by Docetaxel as Adjuvant Chemotherapy Regimen for Chinese Primary Triple Negative Breast Cancer Patients)
该多中心非盲随机对照三期临床研究于2011年7月～2016年4月从全国9家医院入组三阴性乳腺癌术后患者647例，按1∶1的比例随机分为两组进行化疗：新白金方案组（紫杉醇＋卡铂）325例、金标准方案组（环磷酰胺＋表柔比星＋氟尿嘧啶→多西他赛）322例。其中100例（新白金方案组47例、金标准方案组53例）参加过三阴性乳腺癌微环境表型聚类免疫基因组学分型，故对不同免疫表现型患者接受两种化疗方案的无复发生存进行比较，以探索潜在的治疗策略。
结果发现，“免疫热情型肿瘤”与“免疫冷淡型肿瘤”相比：
全部患者：复发或死亡风险相似（风险比：0.68，95%置信区间：0.28～1.66，P=0.40）。
淋巴结阳性患者：复发或死亡风险显著较低（风险比：0.27，95%置信区间：0.07～0.97，P=0.03）
淋巴结阴性患者：复发或死亡风险相似（风险比：1.57，95%置信区间：0.44～5.61，P=0.48）
肿瘤≥2厘米患者：复发或死亡风险较低（风险比：0.29，95%置信区间：0.06～1.30，P=0.08）
肿瘤<2厘米患者：复发或死亡风险相似（风险比：1.76，95%置信区间：0.47～6.57，P=0.39）
新白金化疗患者：复发或死亡风险相似（风险比：0.39，95%置信区间：0.08～1.88，P=0.22）
金标准化疗患者：复发或死亡风险相似（风险比：0.99，95%置信区间：0.33～2.95，P=0.98）
新白金方案与金标准方案相比：
免疫热情型肿瘤：复发或死亡风险相似（风险比：0.39，95%置信区间：0.08～2.01，P=0.24）
免疫冷淡型肿瘤：复发或死亡风险相似（风险比：1.05，95%置信区间：0.39～2.82，P=0.92）
因此，该研究亚组分析结果表明，三阴性乳腺癌的免疫微环境表现型可能对高复发风险（淋巴结阳性、肿瘤较大）患者具有预后意义，对三阴性乳腺癌术后化疗效果的影响仍有待进一步研究。
相关链接
Front Mol Biosci. 2021 Sep 21. Online ahead of print.
Prognostic Effect of Microenvironment Phenotype in Triple-Negative Breast Cancer: Biomarker Analysis of a Prospective Trial.
Si-Yuan Zhu, Ding Ma, Zhi-Ming Shao, Ke-Da Yu.
Fudan University Shanghai Cancer Center, Shanghai, China; Shanghai Medical College, Fudan University, Shanghai, China; Shanghai Key Laboratory of Breast Cancer, Shanghai, China.
BACKGROUND: The microenvironment of triple-negative breast cancer (TNBC) can be divided into three clusters based on bioinformatics-based immunogenomic analysis: the “immune-desert” cluster, the “innate immune-inactivated” cluster, and the “immune-inflamed” cluster. The immune-inflamed cluster is considered as “hot tumor” while the other two are considered as “cold tumor”.
METHODS: To investigate the prognostic effect of microenvironment phenotypes on TNBC, we compared relapse-free survival (RFS) of different phenotypes in 100 patients with RNA sequencing-based expression data from the PATTERN trial (NCT01216111, published in JAMA Oncol 2020), which indicated a superior efficacy of adjuvant paclitaxel-plus-carboplatin regimen compared to the regimen of cyclophosphamide/epirubicin/fluorouracil followed by docetaxel for TNBC. We also analyzed the efficacy of the two regimens for different immune phenotypes to explore potential treatment strategies.
RESULTS: No significant difference in RFS was observed between the “hot tumor” and the “cold tumor” (hazard ratio [HR] = 0.68, 95% confidence interval [CI] 0.28-1.66, P = 0.40). However, the “hot tumor” subtype was associated with significantly longer RFS in node-positive patients (HR = 0.27, 95%CI 0.07-0.97, P = 0.03). Consistently, a similar trend to improved RFS of the “hot tumor” phenotype was detected in patients with stage pT2-3 tumors (HR = 0.29, 95%CI 0.06-1.30, P = 0.08). Furthermore, no significant difference in RFS between the two treatment arms was observed in patients with “hot tumor” (HR = 0.39, 95% CI 0.08-2.01, P = 0.24) or “cold tumor” (HR = 1.05, 95% CI 0.39-2.82, P = 0.92).
CONCLUSION: The microenvironment phenotype in TNBC might have prognostic significance to patients with a high risk of recurrence. The association of the microenvironment phenotypes with the efficacy of adjuvant chemotherapy for TNBC remains to be further studied.
DOI: 10.3389/molb.2021:752154