70基因检测可以改善中等风险早期乳腺癌患者辅助化疗决策
众所周知，乳腺癌HER2检测主要有比较便宜的免疫组化（IHC）和比较贵的原位杂交（ISH）两种方法。当IHC≥+++时，可以认为HER2过表达而进行昂贵的抗HER2治疗，但是当IHC为+～++时，抗HER2治疗有些模棱两可，需要使用ISH进行确认。乳腺癌复发风险的多基因检测也存在类似问题。
目前，乳腺癌复发风险的多基因检测主要有相对便宜的21基因（Oncotype DX）和相对昂贵的70基因（MammaPrint）两种方法。21基因检测采用三分法，将患者的复发风险评为高、中、低三类，由于其中39%～67%被评为不高不低的中等风险，故有可能得到模棱两可的治疗指导。70基因采用两分法，仅将患者分为高风险和低风险两类。那么，对于21基因检测评为中等风险的早期乳腺癌患者，进行70基因特征检测，其结果能否影响医生的治疗决策？
2017年10月26日，《美国医学会杂志肿瘤学分册》在线发表明尼苏达州弗吉尼亚派珀癌症中心、伊利诺伊州洛约拉大学斯特里奇医学院红衣主教贝尔纳丁癌症中心、加利福尼亚州70基因检测公司、威斯康星州密尔沃基奥罗拉高级医疗中心、宾夕法尼亚州圣克莱尔医院、纽约州罗斯韦尔帕克癌症研究所、田纳西州纳什维尔乳腺中心、马里兰州西部医疗系统施瓦布家庭癌症中心、印第安纳州北部癌症研究联盟、弗吉尼亚州林奇堡癌症治疗中心、佛罗里达州迈阿密大学米勒医学院、佛罗里达州莫菲特癌症中心的研究报告，确定了70基因特征检测结果是否与医生辅助治疗决策及其推荐意见信心相关，并且评估了中等风险患者70基因特征检测指数的风险高低和分布情况。
该中等复发评分乳腺癌患者70基因检测前瞻研究（PROMIS）于2012年5月20日～2015年12月31日从美国58个医疗机构入组840例21基因检测复发评分为18～30的HER2阴性且激素受体阳性早期乳腺癌术后患者（平均年龄59岁，范围27～93岁）。接受辅助治疗之前，向医生提供70基因特征检测结果，分析医生收到70基因特征检测结果前后治疗决策的变化，变化大于20%时，使用比值比进行比较。
结果，70基因特征检测840例，其中低风险374例（44.5%）、高风险466例（55.5%）。
70基因特征检测指数分布与21基因检测中等复发评分无关，各个复发评分均有70基因低风险和高风险患者。
医生收到70基因检测结果后，改变治疗决策282例（33.6%）。
所有患者辅助治疗重大改变与70基因检测显著相关（比值比：0.64，95%置信区间：0.50～0.82，P<0.001）。
低风险374例，其中取消化疗108例（28.9%）
高风险466例，其中加入化疗171例（36.7%）
70基因检测结果影响医生辅助治疗推荐意见
高风险466例，推荐辅助化疗409例（87.8%）
低风险374例，反对辅助化疗339例（90.6%）
根据70基因特征检测结果，医生表示对660例（78.6%）治疗推荐意见更有信心。
因此，对于21基因检测分类中等风险患者，70基因特征检测可为临床提供有用信息，并且这些患者超过三分之二的治疗决策发生变化。根据70基因特征检测结果，医生加入或取消化疗。医生收到70基因特征检测结果后，对治疗推荐意见更有信心。
JAMA Oncol. 2017 Oct 26. [Epub ahead of print]
Association of 70-Gene Signature Assay Findings With Physicians' Treatment Guidance for Patients With Early Breast Cancer Classified as Intermediate Risk by the 21-Gene Assay.
Tsai M, Lo S, Audeh W, Qamar R, Budway R, Levine E, Whitworth P, Mavromatis B, Zon R, Oldham D, Untch S, Treece T, Blumencranz L, Soliman H.
Virginia Piper Cancer Center, Minneapolis, Minnesota; Cardinal Bernardin Cancer Center, Loyola University Stritch School of Medicine, Maywood, Illinois; Agendia, Inc, Irvine, California; Aurora Advanced Healthcare, Milwaukee, Wisconsin; St Clair Hospital, Bethel Park, Pennsylvania; Roswell Park Cancer Institute, Buffalo, New York; Nashville Breast Center, Nashville, Tennessee; Western Maryland Health System Schwab Family Cancer Center, Cumberland, Maryland; Northern Indiana Cancer Research Consortium, South Bend, Indiana; Lynchburg Hematology Oncology, Lynchburg, Virginia; Miller School of Medicine, University of Miami, Miami, Florida; Moffitt Cancer Center, Tampa, Florida.
QUESTION: Are 70-gene signature assay findings associated with physicians' treatment decisions for patients with intermediate findings on the 21-gene assay?
FINDINGS: In this study of 840 patients with early breast cancer, 282 physicians (33.6%) changed their treatment decision after receiving the 70-gene assay result. Adjuvant chemotherapy was added and removed so that 88% of high-risk patients were recommended to receive chemotherapy and 91% of low-risk patients were recommended no chemotherapy.
MEANING: The 70-gene signature assay provides clinically actionable information, and the findings may be associated with adjuvant therapy decisions.
IMPORTANCE: Among patients who undergo the 21-gene assay (21-GA), 39% to 67% receive an intermediate risk result and may receive ambiguous treatment guidance. The 70-gene signature assay (70-GS) may be associated with physicians' treatment decisions in this population with early breast cancer.
OBJECTIVE: To determine whether 70-GS findings are associated with physicians' decisions about adjuvant treatment and confidence in their recommendations and to evaluate the dichotomous (high- vs low-risk) and continuous distribution of 70-GS indices among this group of patients with intermediate risk.
DESIGN, SETTING, AND PARTICIPANTS: The Prospective Study of MammaPrint in Breast Cancer Patients With an Intermediate Recurrence Score (PROMIS trial) was an impact study conducted from May 20, 2012, through December 31, 2015, that enrolled 840 patients with early-stage breast cancer and a 21-gene assay recurrence score of 18 to 30. Patients were treated in 58 US institutions.
INTERVENTIONS: The 70-GS result was given to physicians before adjuvant treatment.
MAIN OUTCOMES AND MEASURES: Change in physician treatment decision before vs after receiving the 70-GS result. With a treatment change of greater than 20%, the odds ratio (OR) was applied.
RESULTS: Among the 840 patients who underwent 70-GS classification (mean age, 59 years; range, 27-93 years), 374 (44.5%) had a low-risk and 466 (55.5%) had a high-risk result. The distribution of 70-GS indices did not correlate with recurrence score within the 21-GA intermediate range, with 70-GS low- and high-risk patients observed at every recurrence score. A significant change in adjuvant treatment was associated with receiving the 70-GS classifications with an OR of 0.64 (95% CI, 0.50-0.82; McNemar test, P<.001) for all patients. Among the low-risk patients, 108 of 374 (28.9%) had chemotherapy removed from their treatment recommendation; among the high-risk patients, 171 of 466 (36.7%) had chemotherapy added. Results of the 70-GS were associated with the physician's adjuvant treatment recommendation; 409 high-risk patients (87.8%) were recommended to receive adjuvant chemotherapy, and 339 low-risk patients (90.6%) were recommended no chemotherapy. Physicians reported having greater confidence in their treatment recommendation in 660 cases (78.6%) based on 70-GS results.
CONCLUSIONS AND RELEVANCE: The 70-GS provides clinically actionable information regarding patients classified as intermediate risk by the 21-GA and was associated with a change in treatment decision in 282 of these patients (33.6%). Chemotherapy was added or withheld by the treating physician based on the results of the 70-GS test. Physicians reported more confidence with their treatment recommendation after receiving 70-GS results.
PMID: 29075751
DOI: 10.1001/jamaoncol.2017.3470