提示: 手机请竖屏浏览!

指导乳腺癌辅助治疗的临床和基因组风险
Clinical and Genomic Risk to Guide the Use of Adjuvant Therapy for Breast Cancer


Joseph A. Sparano ... 肿瘤 • 2019.06.20
相关阅读
• 依维莫司治疗绝经后激素受体阳性的晚期乳腺癌 • 氟维司群联合阿那曲唑治疗转移性乳腺癌的患者总生存期

摘要


背景

乳腺癌患者的辅助化疗可通过临床病理因素和用于确定复发风险的21基因检测评分来指导。目前尚不清楚乳腺癌复发的临床风险水平可否为复发评分补充预后信息。

 

方法

我们开展了一项前瞻性试验,试验纳入了9,427例激素受体阳性、人表皮生长因子受体-2阴性、腋窝淋巴结阴性且接受了21基因检测的女性乳腺癌患者,此外我们根据肿瘤大小和组织学分级将乳腺癌复发的临床风险分为低风险或高风险。我们采用Cox比例风险模型计算远处复发的风险比,以此评估临床风险产生的影响。大多数≤50岁的绝经前女性的初始内分泌治疗是他莫昔芬单药治疗。

 

结果

临床风险水平对于以下女性患者的远处复发具有预后意义:21基因复发评分中等(11~25分,评分范围为0~100分,评分较高表示预后较差或接受化疗的潜在获益较大),被随机分配接受内分泌治疗(对高和低临床风险进行比较的风险比,2.73;95%置信区间[CI],1.93~3.87)或被随机分配接受化疗联合内分泌治疗的女性患者(风险比,2.41;95% CI,1.66~3.48),以及复发评分高(26~100分)的女性患者,这些患者全部被分配接受化疗联合内分泌治疗(风险比,3.17;95% CI,1.94~5.19)。在接受单独内分泌治疗的≤50岁女性患者中,复发评分低(评分为0~10分)的患者在9年时的远处复发率估计值(±SE)低于5%(≤1.8%±0.9%),与临床风险无关,而复发评分中等且临床风险低的患者在9年时的远处复发率为4.7%±1.0%。在这一年龄组中,临床风险高、复发评分中等且接受单独内分泌治疗的女性患者(12.3%±2.4%),以及复发评分高且接受化疗联合内分泌治疗的女性患者(15.2%±3.3%)在9年时的远处复发率估计值超过10%。

 

结论

临床风险分层提供了预后信息,将其作为21基因复发评分的补充,可用于识别可从更有效治疗中获益的绝经前女性(由美国国立癌症研究所等资助;在ClinicalTrials.gov注册号为NCT00310180)。





作者信息

Joseph A. Sparano, M.D., Robert J. Gray, Ph.D., Peter M. Ravdin, M.D., Della F. Makower, M.D., Kathleen I. Pritchard, M.D., Kathy S. Albain, M.D., Daniel F. Hayes, M.D., Charles E. Geyer, Jr., M.D., Elizabeth C. Dees, M.D., Matthew P. Goetz, M.D., John A. Olson, Jr., M.D., Ph.D., Tracy Lively, Ph.D., Sunil S. Badve, M.B., B.S., M.D., Thomas J. Saphner, M.D., Lynne I. Wagner, Ph.D., Timothy J. Whelan, B.M., B.Ch., M.S.C., Matthew J. Ellis, M.B., B.Chir., Ph.D., Soonmyung Paik, M.D., William C. Wood, M.D., Maccon M. Keane, M.D., Henry L. Gomez Moreno, M.D., Pavan S. Reddy, M.D., Timothy F. Goggins, M.D., Ingrid A. Mayer, M.D., M.S.C.I., Adam M. Brufsky, M.D., Ph.D., Deborah L. Toppmeyer, M.D., Virginia G. Kaklamani, M.D., D.Sc., Jeffrey L. Berenberg, M.D., Jeffrey Abrams, M.D., and George W. Sledge, Jr., M.D.
From Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY (J.A.S., D.F.M.); Dana–Farber Cancer Institute, Boston (R.J.G.); University of Texas, San Antonio (P.M.R.); Sunnybrook Research Institute, Toronto (K.I.P.), and McMaster University, 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.), and Duke University Medical Center, Durham (J.A.O., J.A.) — both in North Carolina; Mayo Clinic, Jacksonville, FL (M.P.G.); National Institutes of Health, National Cancer Institute, Bethesda, MD (T.L.); Indiana University School of Medicine (S.S.B.) and Indiana University Hospital (G.W.S.), Indianapolis; Vince Lombardi Cancer Clinic, Two Rivers (T.J.S.), and Fox Valley Hematology and Oncology, Appleton (T.F.G.) — both in Wisconsin; Washington University, St. Louis (M.J.E.); the National Surgical Adjuvant Breast and Bowel Project Pathology Office (S.P.) and the University of Pittsburgh (A.M.B.), Pittsburgh; Emory University, Atlanta (W.C.W.); Cancer Trials Ireland, Dublin (M.M.K.); Instituto Nacional de Enfermedades Neoplasicas, 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.); and the University of Hawaii Cancer Center, Honolulu (J.L.B.). Address reprint requests to Dr. Sparano at Montefiore Medical Center, 1695 Eastchester Rd., Bronx, NY 10461, or at jsparano@montefiore.org.

 

参考文献

1. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005;365:1687-1717.

2. Paik S, Shak S, Tang G, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med 2004;351:2817-2826.

3. Paik S, Tang G, Shak S, et al. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol 2006;24:3726-3734.

4. Albain KS, Barlow WE, Shak S, et al. Prognostic and predictive value of the 21-gene Recurrence Score assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomised trial. Lancet Oncol 2010;11:55-65.

5. Sparano JA, Paik S. Development of the 21-gene assay and its application in clinical practice and clinical trials. J Clin Oncol 2008;26:721-728.

6. Geyer CE Jr, Tang G, Mamounas EP, et al. 21-Gene assay as predictor of chemotherapy benefit in HER2-negative breast cancer. NPJ Breast Cancer 2018;4:37-37.

7. Sparano JA, Gray RJ, Makower DF, et al. Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer. N Engl J Med 2018;379:111-121.

8. Sparano JA, Gray RJ, Makower DF, et al. Prospective validation of a 21-gene expression assay in breast cancer. N Engl J Med 2015;373:2005-2014.

9. Hudis CA, Barlow WE, Costantino JP, et al. Proposal for standardized definitions for efficacy end points in adjuvant breast cancer trials: the STEEP system. J Clin Oncol 2007;25:2127-2132.

10. Olivotto IA, Bajdik CD, Ravdin PM, et al. Population-based validation of the prognostic model Adjuvant! for early breast cancer. J Clin Oncol 2005;23:2716-2725.

11. Mook S, Schmidt MK, Rutgers EJ, et al. Calibration and discriminatory accuracy of prognosis calculation for breast cancer with the online Adjuvant! program: a hospital-based retrospective cohort study. Lancet Oncol 2009;10:1070-1076.

12. Cardoso F, van’t Veer LJ, Bogaerts J, et al. 70-Gene signature as an aid to treatment decisions in early-stage breast cancer. N Engl J Med 2016;375:717-729.

13. Goldstein LJ, Gray R, Badve S, et al. Prognostic utility of the 21-gene assay in hormone receptor-positive operable breast cancer compared with classical clinicopathologic features. J Clin Oncol 2008;26:4063-4071.

14. Tang G, Shak S, Paik S, et al. Comparison of the prognostic and predictive utilities of the 21-gene Recurrence Score assay and Adjuvant! for women with node-negative, ER-positive breast cancer: results from NSABP B-14 and NSABP B-20. Breast Cancer Res Treat 2011;127:133-142.

15. Tang G, Cuzick J, Costantino JP, et al. Risk of recurrence and chemotherapy benefit for patients with node-negative, estrogen receptor-positive breast cancer: recurrence score alone and integrated with pathologic and clinical factors. J Clin Oncol 2011;29:4365-4372.

16. Dowsett M, Turner N. Estimating risk of recurrence for early breast cancer: integrating clinical and genomic risk. J Clin Oncol 2019;37:689-692.

17. Wang R, Lagakos SW, Ware JH, Hunter DJ, Drazen JM. Statistics in medicine — reporting of subgroup analyses in clinical trials. N Engl J Med 2007;357:2189-2194.

18. Hortobagyi GN, Shak S, Sledge GW Jr, et al. Breast cancer-specific mortality (BCSM) in patients (pts) with node-negative (N0) and node-positive (N+) breast cancer (BC) guided by the 21-gene assay: a SEER-genomic population-based study. Cancer Res 2019;799:4 Suppl:P3-11-02. abstract.

19. Walshe JM, Denduluri N, Swain SM. Amenorrhea in premenopausal women after adjuvant chemotherapy for breast cancer. J Clin Oncol 2006;24:5769-5779.

20. Swain SM, Jeong J-H, Geyer CE Jr, et al. Longer therapy, iatrogenic amenorrhea, and survival in early breast cancer. N Engl J Med 2010;362:2053-2065.

21. Francis PA, Regan MM, Fleming GF, et al. Adjuvant ovarian suppression in premenopausal breast cancer. N Engl J Med 2015;372:436-446.

22. Francis PA, Pagani O, Fleming GF, et al. Tailoring adjuvant endocrine therapy for premenopausal breast cancer. N Engl J Med 2018;379:122-137.

23. Paik S, Tang G, Kim C, et al. Expression of the 21 genes in the Recurrence Score assay and tamoxifen clinical benefit in the NSABP study B-14 of node negative, estrogen receptor positive breast cancer. J Clin Oncol 2005;16:Suppl:510-510. abstract.

24. Kim C, Tang G, Pogue-Geile KL, et al. Estrogen receptor (ESR1) mRNA expression and benefit from tamoxifen in the treatment and prevention of estrogen receptor-positive breast cancer. J Clin Oncol 2011;29:4160-4167.

25. Goss PE, Ingle JN, Martino S, et al. A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer. N Engl J Med 2003;349:1793-1802.

26. Wolmark N, Mamounas EP, Baehner FL, et al. Prognostic impact of the combination of Recurrence Score and quantitative estrogen receptor expression (ESR1) on predicting late distant recurrence risk in estrogen receptor-positive breast cancer after 5 years of tamoxifen: results from NRG Oncology/National Surgical Adjuvant Breast and Bowel Project B-28 and B-14. J Clin Oncol 2016;34:2350-2358.

27. Early Breast Cancer Trialists’ Collaborative Group. Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet 2012;379:432-444.

28. Mamounas EP, Tang G, Liu Q. The importance of systemic therapy in minimizing local recurrence after breast-conserving surgery: the NSABP experience. J Surg Oncol 2014;110:45-50.

29. Bertelsen L, Bernstein L, Olsen JH, et al. Effect of systemic adjuvant treatment on risk for contralateral breast cancer in the Women’s Environment, Cancer and Radiation Epidemiology Study. J Natl Cancer Inst 2008;100:32-40.

30. Fisher B, Dignam J, Wolmark N, et al. Tamoxifen and chemotherapy for lymph node-negative, estrogen receptor-positive breast cancer. J Natl Cancer Inst 1997;89:1673-1682.

服务条款 | 隐私政策 | 联系我们