Mammostrat As an Immunohistochemical Multigene Assay for Prediction of Early Relapse Risk in the Tamoxifen Versus Exemestane Adjuvant Multicenter Trial Pathology Study

Mammostrat As an Immunohistochemical Multigene Assay for Prediction of Early Relapse Risk in the Tamoxifen Versus Exemestane Adjuvant Multicenter Trial Pathology Study
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DOI:
10.1200/jco.2012.42.8896
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发表时间:
2012-12-20
影响因子:
45.3
通讯作者:
Rea, Daniel
Rea, Daniel
中科院分区:
医学1区
文献类型:
--
作者:
Bartlett, John M. S.;Bloom, Kenneth J.;Rea, Daniel

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一些激素敏感型早期乳腺癌的绝经后患者尽管接受内分泌治疗,但仍有很高的复发风险,此外,辅助化疗也可能受益。挑战是前瞻性地识别这类患者。Mammostrat试验使用五种免疫组织化学标志物对患者的复发风险进行分层,并可能为治疗决策提供信息。我们在他莫昔芬与依西美坦辅助的多中心(STEAM)试验中测试了该小组的疗效。队列中47%的患者结节阳性,36%的患者接受辅助化疗。3个0.6 mm(2)的TMA核心进行染色,并检测P53、HTF9C、CEACAM5、NDRG1和SLC7A5的阳性表达。结果在对常规临床病理指标进行校正的多因素回归分析中,Mammostrat为未接受化疗的雌激素受体(ER)阳性结节阴性患者(n=1226)内分泌治疗后的无复发生存率(DRFS)提供了显著的补充信息(P=0.004)。在所有未接受化疗的患者(n=2,559)和整个队列(n=3,837)中进行的额外分析显示,Mammostrat评分提供了这些组中有关DRFS的额外信息(P=.001和P
PurposeSome postmenopausal patients with hormone-sensitive early breast cancer remain at high risk of relapse despite endocrine therapy and, in addition, might benefit from adjuvant chemotherapy. The challenge is to prospectively identify such patients. The Mammostrat test uses five immunohistochemical markers to stratify patients regarding recurrence risk and may inform treatment decisions. We tested the efficacy of this panel in the Tamoxifen versus Exemestane Adjuvant Multicenter (TEAM) trial.Patients and MethodsPathology blocks from 4,598 TEAM patients were collected, and tissue microarrays (TMAs) were constructed. The cohort was 47% node-positive, and 36% of patients in the cohort were treated with adjuvant chemotherapy. Triplicate 0.6-mm(2) TMA cores were stained, and positivity for p53, HTF9C, CEACAM5, NDRG1, and SLC7A5 was assessed. Cases were assigned a Mammostrat risk score, and distant relapse-free survival (DRFS) and disease-free survival (DFS) were analyzed.ResultsIn multivariate regression analyses, which were corrected for conventional clinicopathologic markers, Mammostrat provided significant additional information on DRFS after endocrine therapy in estrogen receptor (ER) -positive node-negative patients (n = 1,226) who did not receive chemotherapy (P=.004). Additional analyses in all patients not exposed to chemotherapy, irrespective of nodal status (n = 2,559) and in the entire cohort (n = 3,837) showed Mammostrat scores provided additional information on DRFS in these groups (P=.001 and P