Mamounas Eleftherios P, Liu Qing, Paik Soonmyung, Baehner Frederick L, Tang Gong, Jeong Jong-Hyeon, Kim S Rim, Butler Steven M, Jamshidian Farid, Cherbavaz Diana B, Sing Amy P, Shak Steven, Julian Thomas B, Lembersky Barry C, Wickerham D Lawrence, Costantino Joseph P, Wolmark Norman
Affiliations of authors: National Surgical Adjuvant Breast and Bowel Project (NSABP Legacy trials are now a part of the NRG Oncology portfolio), Pittsburgh, PA (EPM, SP, SRK, TBJ, BCL, DLW, NW); UF Health Cancer Center at Orland Health, Orlando, FL (EPM); NRG Oncology, Pittsburgh, PA (QL, GT, JHJ, JPC); University of Pittsburgh, Pittsburgh, PA (QL, GT, JHJ, JPC); Severance Biomedical Science Institute and Department of Medical Oncology, Yonsei University College of Medicine, Seoul, Korea (SP); Genomic Health, Inc., Redwood City, CA (FLB, SMB, FJ, DBC, APS, SS); Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA (TBJ, DLW, NW); University of Pittsburgh Medical Center, Pittsburgh, PA (BCL).
J Natl Cancer Inst. 2017 Jan 25;109(4). doi: 10.1093/jnci/djw259. Print 2017 Jan.
The 21-gene recurrence score (RS) predicts risk of locoregional recurrence (LRR) in node-negative, estrogen receptor (ER)-positive breast cancer. We evaluated the association between RS and LRR in node-positive, ER-positive patients treated with adjuvant chemotherapy plus tamoxifen in National Surgical Adjuvant Breast and Bowel Project B-28.
B-28 compared doxorubicin/cyclophosphamide (AC X 4) with AC X 4 followed by paclitaxel X 4. Tamoxifen was given to patients age 50 years or older and those younger than age 50 years with ER-positive and/or progesterone receptor-positive tumors. Lumpectomy patients received breast radiotherapy. Mastectomy patients received no radiotherapy. The present study includes 1065 ER-positive, tamoxifen-treated patients with RS assessment. Cumulative incidence functions and subdistribution hazard regression models were used for LRR to account for competing risks including distant recurrence, second primary cancers, and death from other causes. Median follow-up was 11.2 years. All statistical tests were one-sided.
There were 80 LRRs (7.5%) as first events (68% local/32% regional). RS was low: 36.2%; intermediate: 34.2%; and high: 29.6%. RS was a statistically significant predictor of LRR in univariate analyses (10-year cumulative incidence of LRR = 3.3%, 7.2%, and 12.2% for low, intermediate, and high RS, respectively, P < .001). In multivariable regression analysis, RS remained an independent predictor of LRR (hazard ratio [HR] = 2.59, 95% confidence interval [CI] = 1.28 to 5.26, for a 50-point difference, P = .008) along with pathologic nodal status (HR = 1.91, 95% CI = 1.20 to 3.03, for four or more vs one to three positive nodes, P = .006) and tumor size (HR = 1.28, 95% CI = 1.05 to 1.55, for a 1 cm difference, P = .02).
RS statistically significantly predicts risk of LRR in node-positive, ER-positive breast cancer patients after adjuvant chemotherapy plus tamoxifen. These findings can help in the selection of appropriate candidates for comprehensive radiotherapy.
21基因复发评分（RS）可预测淋巴结阴性、雌激素受体（ER）阳性乳腺癌患者的局部区域复发（LRR）风险。我们在国家外科辅助乳腺和肠道项目B-28中评估了RS与接受辅助化疗加他莫昔芬治疗的淋巴结阳性、ER阳性患者LRR之间的关联。
B-28研究比较了多柔比星/环磷酰胺（AC×4）与AC×4序贯紫杉醇×4的疗效。50岁及以上患者以及50岁以下ER阳性和/或孕激素受体阳性肿瘤患者接受他莫昔芬治疗。保乳手术患者接受乳腺放疗。乳房切除术患者未接受放疗。本研究纳入了1065例接受他莫昔芬治疗且进行了RS评估的ER阳性患者。采用累积发病率函数和亚分布风险回归模型分析LRR，以考虑包括远处复发、第二原发性癌症和其他原因导致的死亡等竞争风险。中位随访时间为11.2年。所有统计检验均为单侧检验。
共有80例（7.5%）患者首次出现LRR（68%为局部复发/32%为区域复发）。RS低的患者占36.2%；中等的占34.2%；高的占29.6%。在单因素分析中，RS是LRR的统计学显著预测因素（低、中、高RS患者10年LRR累积发病率分别为3.3%、7.2%和12.2%，P <.001）。在多变量回归分析中，RS仍然是LRR的独立预测因素（风险比[HR]=2.59，95%置信区间[CI]=1.28至5.26，相差50分，P =.008），同时还有病理淋巴结状态（HR = 1.91，95% CI = 1.20至3.03，四个或更多阳性淋巴结与一至三个阳性淋巴结相比，P =.006）和肿瘤大小（HR = 1.28，95% CI = 1.05至1.55，相差1 cm，P =.02）。
RS在统计学上显著预测了接受辅助化疗加他莫昔芬治疗的淋巴结阳性、ER阳性乳腺癌患者的LRR风险。这些发现有助于选择合适的患者进行综合放疗。
