21基因表达检测法在乳腺癌中的前瞻性验证
Prospective Validation of a 21-Gene Expression Assay in Breast Cancer.
作者信息
Sparano Joseph A, Gray Robert J, Makower Della F, Pritchard Kathleen I, Albain Kathy S, Hayes Daniel F, Geyer Charles E, Dees Elizabeth C, Perez Edith A, Olson John A, Zujewski JoAnne, Lively Tracy, Badve Sunil S, Saphner Thomas J, Wagner Lynne I, Whelan Timothy J, Ellis Matthew J, Paik Soonmyung, Wood William C, Ravdin Peter, Keane Maccon M, Gomez Moreno Henry L, Reddy Pavan S, Goggins Timothy F, Mayer Ingrid A, Brufsky Adam M, Toppmeyer Deborah L, Kaklamani Virginia G, Atkins James N, Berenberg Jeffrey L, Sledge George W
机构信息
From the Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY (J.A.S., D.F.M.); Dana-Farber Cancer Institute, Boston (R.J.G.); Sunnybrook Research Institute, Toronto (K.I.P.) and Juravinski Cancer Center, Hamilton, ON (T.J.W.) - both in Canada; Loyola University Medical Center, Maywood (K.S.A.), and Northwestern University, Chicago (L.I.W., V.G.K.) - both in Illinois; University of Michigan, Ann Arbor (D.F.H.); Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond (C.E.G.); University of North Carolina, Chapel Hill (E.C.D.), Duke University Medical Center, Durham (J.A.O.), Wake Forest University Health Service, Winston-Salem (L.I.W.), and Southeast Clinical Oncology Research Consortium, Goldsboro (J.N.A.) - all in North Carolina; Mayo Clinic, Jacksonville, FL (E.A.P.); University of Maryland School of Medicine, Baltimore (J.A.O.), and National Institutes of Health, Bethesda (J.Z., T.L.) - both in Maryland; Indiana University School of Medicine (S.S.B.) and Indiana University Hospital (G.W.S.) - both in Indianapolis; Vince Lombardi Cancer Clinic, Two Rivers (T.J.S.), and Fox Valley Hematology and Oncology, Appleton (T.F.G.) - both in Wisconsin; Baylor College of Medicine, Houston (M.J.E.), and University of Texas, San Antonio (P.R.) - both in Texas; Washington University, St. Louis (M.J.E.); Allegheny General Hospital (S.P.) and University of Pittsburgh (A.M.B.) - both in Pittsburgh; the Department of Medical Oncology and Breast Center, Yonsei University College of Medicine, Seoul, South Korea (S.P.); Emory University, Atlanta (W.C.W.); Irish Clinical Oncology Research Group, Dublin (M.M.K.); Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru (H.L.G.M.); Cancer Center of Kansas, Wichita (P.S.R.); Vanderbilt University, Nashville (I.A.M.); Rutgers Cancer Institute of New Jersey, New Brunswick (D.L.T.); University of Hawaii Cancer Center, Honolulu (J.L.B.); and Stanford University, Stanford, CA (G.W.S.)
出版信息
N Engl J Med. 2015 Nov 19;373(21):2005-14. doi: 10.1056/NEJMoa1510764. Epub 2015 Sep 27.
BACKGROUND
Prior studies with the use of a prospective-retrospective design including archival tumor samples have shown that gene-expression assays provide clinically useful prognostic information. However, a prospectively conducted study in a uniformly treated population provides the highest level of evidence supporting the clinical validity and usefulness of a biomarker.
METHODS
We performed a prospective trial involving women with hormone-receptor-positive, human epidermal growth factor receptor type 2 (HER2)-negative, axillary node-negative breast cancer with tumors of 1.1 to 5.0 cm in the greatest dimension (or 0.6 to 1.0 cm in the greatest dimension and intermediate or high tumor grade) who met established guidelines for the consideration of adjuvant chemotherapy on the basis of clinicopathologic features. A reverse-transcriptase-polymerase-chain-reaction assay of 21 genes was performed on the paraffin-embedded tumor tissue, and the results were used to calculate a score indicating the risk of breast-cancer recurrence; patients were assigned to receive endocrine therapy without chemotherapy if they had a recurrence score of 0 to 10, indicating a very low risk of recurrence (on a scale of 0 to 100, with higher scores indicating a greater risk of recurrence).
RESULTS
Of the 10,253 eligible women enrolled, 1626 women (15.9%) who had a recurrence score of 0 to 10 were assigned to receive endocrine therapy alone without chemotherapy. At 5 years, in this patient population, the rate of invasive disease-free survival was 93.8% (95% confidence interval [CI], 92.4 to 94.9), the rate of freedom from recurrence of breast cancer at a distant site was 99.3% (95% CI, 98.7 to 99.6), the rate of freedom from recurrence of breast cancer at a distant or local-regional site was 98.7% (95% CI, 97.9 to 99.2), and the rate of overall survival was 98.0% (95% CI, 97.1 to 98.6).
CONCLUSIONS
Among patients with hormone-receptor-positive, HER2-negative, axillary node-negative breast cancer who met established guidelines for the recommendation of adjuvant chemotherapy on the basis of clinicopathologic features, those with tumors that had a favorable gene-expression profile had very low rates of recurrence at 5 years with endocrine therapy alone. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00310180.).
背景
先前使用包括存档肿瘤样本在内的前瞻性-回顾性设计的研究表明，基因表达检测可提供临床上有用的预后信息。然而，在接受统一治疗的人群中进行的前瞻性研究为支持生物标志物的临床有效性和实用性提供了最高水平的证据。
方法
我们进行了一项前瞻性试验，纳入了激素受体阳性、人表皮生长因子受体2（HER2）阴性、腋窝淋巴结阴性的乳腺癌女性患者，这些患者的肿瘤最大直径为1.1至5.0 cm（或最大直径为0.6至1.0 cm且肿瘤分级为中级或高级），符合基于临床病理特征考虑辅助化疗的既定指南。对石蜡包埋的肿瘤组织进行了21个基因的逆转录聚合酶链反应检测，并将结果用于计算一个表明乳腺癌复发风险的评分；如果复发评分为0至10分（表明复发风险非常低，范围为0至100分，分数越高表明复发风险越大），则患者被分配接受内分泌治疗而不进行化疗。
结果
在纳入的10253名符合条件的女性中，1626名（15.9%）复发评分为0至10分的女性被分配仅接受内分泌治疗而不进行化疗。在该患者群体中，5年时无侵袭性疾病生存率为93.8%（95%置信区间[CI]，92.4至94.9），远处部位无乳腺癌复发率为99.3%（95%CI，98.7至99.6），远处或局部区域部位无乳腺癌复发率为98.7%（95%CI，97.9至99.2），总生存率为98.0%（95%CI，97.1至98.6）。
结论
在基于临床病理特征符合辅助化疗推荐既定指南的激素受体阳性、HER2阴性、腋窝淋巴结阴性的乳腺癌患者中，那些肿瘤具有良好基因表达谱的患者仅接受内分泌治疗时5年复发率非常低。（由美国国立癌症研究所等资助；ClinicalTrials.gov编号，NCT00310180。）
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