c-MYC 蛋白表达对接受曲妥珠单抗辅助治疗的早期 HER2+乳腺癌患者结局的影响：NCCTG（联盟）N9831 研究
Impact of c-MYC protein expression on outcome of patients with early-stage HER2+ breast cancer treated with adjuvant trastuzumab NCCTG (alliance) N9831.
机构信息
Authors' Affiliations: Section of Biostatistics; Division of Anatomic Pathology, Mayo Clinic, Scottsdale, Arizona; Division of Experimental Pathology, Department of Laboratory Medicine and Pathology; Division of Biomedical Statistics and Informatics and Medical Oncology, Mayo Clinic, Rochester, Minnesota; Division of Anatomic Pathology and Hematology/Oncology, Mayo Clinic, Jacksonville, Florida; Division of Hematology/Oncology, University of Pittsburgh Cancer Institute and UPMC Cancer Center, Pittsburgh, Pennsylvania; The Angeles Clinic and Research Institute, Santa Monica, California; Indiana University Medical Center Cancer Pavilion, Indianapolis, Indiana; Division of Hematology/Oncology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire; Oncology Associates of Cedar Rapids, Cedar Rapids, Iowa; Seattle Cancer Care Alliance, Seattle, Washington; and Case Western Reserve University, Cleveland, Ohio.
出版信息
Clin Cancer Res. 2013 Oct 15;19(20):5798-807. doi: 10.1158/1078-0432.CCR-13-0558. Epub 2013 Aug 21.
PURPOSE
This study investigated the association between tumor MYC protein expression and disease-free survival (DFS) of patients randomized to receive chemotherapy alone (Arm A) or chemotherapy with sequential (Arm B) or concurrent trastuzumab (Arm C) in the N9831 (Alliance) adjuvant HER2(+) trastuzumab breast cancer trial.
EXPERIMENTAL DESIGN
This analysis included 1,736 patients randomized to Arms A, B, and C on N9831. Nuclear MYC protein expression was determined in tissue microarray sections containing three biopsies per patient or whole tissue sections using standard immunohistochemistry (clone 9E10). A tumor was considered positive for MYC protein overexpression (MYC(+)) if the nuclear 3+ staining percentage was more than 30%.
RESULTS
Five hundred and seventy-four (33%) tumors were MYC(+). MYC(+) was associated with hormone receptor positivity (χ(2), P = 0.006), tumors 2 cm or more (χ(2), P = 0.02), and a higher rate of nodal positivity (χ(2), P < 0.001). HRs for DFS (median follow-up: 6.1 years) for Arm C versus A were 0.52 (P = 0.006) and 0.65 (P = 0.006) for patients with MYC(+) and MYC(-) tumors, respectively (P(interaction) = 0.40). For Arm B versus A, HRs for patients with MYC(+) and MYC(-) tumors were 0.79 (P = 0.21) and 0.74 (P = 0.04), respectively (P(interaction) = 0.71). For Arm C versus B, HRs for patients with MYC(+) and MYC(-) tumors were 0.56 (P = 0.02) and 0.89 (P = 0.49), respectively (P(interaction) = 0.17).
CONCLUSIONS
Our data do not support an impact of tumor MYC protein expression on differential benefit from adjuvant trastuzumab.
目的
本研究旨在探讨肿瘤 MYC 蛋白表达与 N9831（Alliance）辅助 HER2（+）曲妥珠单抗乳腺癌试验中接受单纯化疗（Arm A）或化疗序贯（Arm B）或同期曲妥珠单抗（Arm C）治疗的患者无病生存期（DFS）之间的关联。
实验设计
本分析纳入了 N9831 试验中随机分配至 Arm A、B 和 C 的 1736 名患者。使用标准免疫组织化学（克隆 9E10）在包含每个患者三个活检的组织微阵列切片或整个组织切片中确定核 MYC 蛋白表达。如果核 3+染色百分比超过 30%，则认为肿瘤存在 MYC 蛋白过表达（MYC(+）。
结果
574 例（33%）肿瘤为 MYC(+）。MYC(+)与激素受体阳性（χ²，P = 0.006）、肿瘤 2cm 或更大（χ²，P = 0.02）和更高的淋巴结阳性率（χ²，P < 0.001）相关。Arm C 与 Arm A 相比，DFS 的 HR（中位随访：6.1 年）对于 MYC(+)和 MYC(-)肿瘤患者分别为 0.52（P = 0.006）和 0.65（P = 0.006）（P(interaction) = 0.40）。对于 Arm B 与 Arm A 相比，MYC(+)和 MYC(-)肿瘤患者的 HR 分别为 0.79（P = 0.21）和 0.74（P = 0.04）（P(interaction) = 0.71）。对于 Arm C 与 Arm B 相比，MYC(+)和 MYC(-)肿瘤患者的 HR 分别为 0.56（P = 0.02）和 0.89（P = 0.49）（P(interaction) = 0.17）。
结论
我们的数据不支持肿瘤 MYC 蛋白表达对辅助曲妥珠单抗治疗的差异化获益有影响。
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