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自从乳腺癌筛查普及以来，早期乳腺癌发现率有所增加，这就产生了一定程度的过度诊断和过度治疗。了解肿瘤基因特征可能有助于临床医师确定长期预后良好的亚组，并有助于避免早期乳腺癌的过度治疗。对于激素受体阳性HER2阴性早期乳腺癌术后患者，如果70基因（MammaPrint）评分为超低风险，那么化疗意义不大，仅予内分泌治疗即可，有助于避免过度治疗，不过既往研究样本量较小。 2022年1月21日，美国临床肿瘤学会《临床肿瘤学杂志》在线发表荷兰癌症研究院、欧洲癌症研究与治疗组织、比利时布鲁塞尔自由大学朱尔博代研究所、葡萄牙尚帕利莫基金会临床中心、美国旧金山加利福尼亚大学海伦迪勒家族综合癌症中心的MINDACT研究长期随访分层分析结果，对目前为止最大样本队列评估了超低风险患者的临床结局。 MINDACT (Microarray In Node-Negative and 1 to 3 Positive Lymph Node Disease May Avoid Chemotherapy): A Prospective, Randomized Study Comparing the 70-Gene Signature With the Common Clinical-Pathological Criteria in Selecting Patients for Adjuvant Chemotherapy in Breast Cancer With 0 to 3 Positive Nodes (NCT00433589, EudraCT 2005-002625-31, EORTC-10041, BIG-3-04) 作者对2007年2月8日至2011年7月11日入组MINDACT研究的6693例激素受体阳性HER2阴性早期乳腺癌患者进行分析，其中1000例患者（15%）70基因评分为超低风险，年龄>50岁占67%，肿瘤≤2厘米占81%，淋巴结阴性占80%，1或2级肿瘤占96%，雌激素受体阳性占99%。根据生存曲线分析和多因素比例风险回归风险比及其95%置信区间，按70基因评分结果（高、低和超低）对患者进行分层，对无远处转移生存和乳腺癌相关生存进行评定。 结果，中位随访8.7年，84%的患者接受了术后全身辅助治疗（69%为内分泌治疗，14%为内分泌治疗＋化疗，1%为其他），16%的患者未接受术后全身辅助治疗。 1000例超低风险患者与3295例低风险患者相比：  全部患者按21基因风险比较
 临床低风险患者按21基因风险比较
 21基因超低风险患者按临床风险高低比较
 21基因超低风险患者按术后不同辅助治疗比较
因此，该研究分层分析结果表明，70基因评分超低风险患者预后最佳，无论临床风险如何，与低风险患者相比，发生远处转移或乳腺癌相关死亡的风险显著较低，8年乳腺癌相关生存率高于99%，极少数患者发生远处转移，8年无远处转移生存率达97%，这些患者可以成为进一步降级治疗的候选者，以避免过度治疗及其副作用风险。70基因评分超低风险可用于将来调查内分泌治疗降级的研究，以更好地平衡获益和危害。
不过，激素受体阳性早期乳腺癌患者大多数复发于术后至少10年甚至20年，该研究样本量虽然最大，但是中位随访8.7年可能有些早。 相关链接 J Clin Oncol. 2022 Jan 21. Online ahead of print.
Outcome of Patients With an Ultralow-Risk 70-Gene Signature in the MINDACT Trial. Lopes Cardozo JMN, Drukker CA, Rutgers EJT, Schmidt MK, Glas AM, Witteveen A, Cardoso F, Piccart M, Esserman LJ, Poncet C, van 't Veer LJ. Netherlands Cancer Institute, Amsterdam, the Netherlands; Agendia NV, Amsterdam, the Netherlands; European Organisation for Research and Treatment of Cancer (EORTC) Headquarters, Brussels, Belgium; Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium; Champalimaud Clinical Center/Champalimaud Foundation, Lisbon, Portugal; UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA. PURPOSE: Patients with 70-gene signature ultralow-risk breast cancers have shown excellent survival in historic cohorts, including randomized trials. The ultralow-risk subgroup was characterized to help avoid overtreatment. We evaluated outcomes of ultralow-risk patients in the largest cohort to date. METHODS: Of the 6,693 patients enrolled in the EORTC-10041/BIG-3-04 randomized phase III MINDACT trial, profiling revealed an ultralow-risk 70-gene signature in 1,000 patients (15%). Distant metastasis-free interval (DMFI) and breast cancer-specific survival (BCSS) were assessed in patients stratified by 70-gene signature result (high, low, and ultralow) by Kaplan-Meier analysis and hazard ratios with 95% CI from Cox regression. RESULTS: Median follow-up was 8.7 years. Of the ultralow-risk patients (n = 1,000), 67% were > 50 years, 81% had tumors ≤ 2 cm, 80% were lymph node-negative, 96% had grade 1 or 2 tumors, and 99% were estrogen receptor (ER)-positive. Systemic therapy was received by 84% of patients (69% endocrine therapy, 14% endocrine therapy plus chemotherapy, 1% other) and 16% received no adjuvant systemic treatment. The 8-year DMFI for ultralow-risk patients was 97.0% (95% CI, 95.8 to 98.1), which was 2.5% higher than for patients with low-risk tumors (n = 3,295, 94.5% [95% CI, 93.6 to 95.3]). The hazard ratio for DMFI was 0.65 (95% CI, 0.45 to 0.94) for ultralow versus low risk, after adjusting for clinical-pathologic and treatment characteristics. The 8-year BCSS for ultralow-risk patients was 99.6% (95% CI, 99.1 to 100). CONCLUSION: Patients with an ultralow-risk 70-gene signature have the best prognosis, distinctive from low risk, with 8-year BCSS above 99%, and very few patients developed distant metastases with an 8-year DMFI rate of 97%. These patients could be candidates for further de-escalation of treatment, to avoid overtreatment and the risk of side effects. KEY OBJECTIVE: There has been an increase in the incidence of early-stage breast cancers since the introduction of population-based screening, which in part represents overdiagnosis. Knowledge of the tumor biology may help to identify a subgroup with an excellent long-term prognosis and could aid in avoiding overtreatment in early-stage breast cancer. Patients with 70-gene signature ultralow-risk tumors have excellent long-term survival in historic cohorts. We assessed survival outcomes of patients with an ultralow-risk 70-gene signature in the prospective MINDACT trial, the largest cohort to date. KNOWLEDGE GENERATED: 70-gene signature ultralow-risk patients had an 8-year breast cancer-specific survival of 99%, regardless of clinical risk, and their risk of distant metastasis or breast cancer-related death is significantly lower compared to patients with low-risk tumors. RELEVANCE: The 70-gene signature ultralow risk could be used in future trials investigating the de-escalation of endocrine therapy to better balance benefits and harms. PMID: 35061525 DOI: 10.1200/JCO.21.02019 
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