HER2 borderline is a negative prognostic factor for primary malignant breast cancer
HER2 borderline is a negative prognostic factor for primary malignant breast cancer
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DOI：
10.1007/s10549-020-05608-3
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发表时间：
2020-03-31
影响因子：
3.8
通讯作者：
Dutt, Shilpee
中科院分区：
文献类型：
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作者：
Bhattacharjee, Atanu;Rajendra, Jacinth;Dutt, Shilpee
背景：人表皮生长因子受体2(HER2)基因扩增和蛋白过度表达是乳腺癌重要的预测、预后指标和治疗靶点，强调HER2阳性和阴性患者分类的重要性。然而，从免疫组织化学评分来看，2%的患者既不是HER2+也不是-VE，而是处于HER2B的交界处。要对这些患者做出知情的治疗决定，重要的是要知道这一组与HER-2阳性/阴性相比有多大不同。方法对来自监测、流行病学和最终结果(SEER)数据库的104,668例乳腺癌患者样本进行分析。生存分析采用开源R(Cran Project R version3.5.0)“Survival”程序包。采用Coxph函数计算具有可信区间的危险比。结果104,668例中，HER2阳性2239例(2.13%)，HER2阴性87,157例(83.26%)，HER2阳性15,272例(14.6%)。以乳腺癌为主的恶性肿瘤占84944例(81.16%)。在原发恶性乳腺癌患者中，HER2阴性患者的风险比显著高于HER2阳性患者样本(HR=0.772，95%CI 0.715~0.833，p=.001)，而HER2阳性患者中HER2阴性患者的风险比并不明显(HR=.919，95%CI 0.797~1.06，p=.248)。最重要的是，在PMBC患者中，与HER2阴性患者相比，HER2阴性患者的HR较差(HR=1.354，95%CI 1.126-1.627，p=0.001.)。结论这是首次有大量的患者样本和显着的统计学力量证明HER2临界值代表PMBC的负面预后因素的报道。从而为在HER2边缘患者中进行HER2靶向治疗的对照临床试验提供了理论依据。
Background HER-(human epidermal growth factor receptor 2) gene amplification and protein overexpression are important predictive, prognosis markers, and therapeutic target for breast cancer, emphasizing the importance of categorizing patients into HER2 positive and negative. However, from immunohistochemistry scores, 2% patients are neither HER2 + nor -ve, but borderline called HER2B. To make informed treatment decisions of these patients, it is important to know how different this group is compared to HER-2 positive/negative. Methods We analyzed n = 104,668 breast cancer patient samples from Surveillance, Epidemiology, and End Results (SEER) database. Survival analysis was performed using open source R (Cran project R version 3.5.0) "survival" package. Hazard ratio with confidence intervals was computed using coxph function. Results Of n = 104,668, 2239 (2.13%) patients were HER2 borderline, 87,157 (83.26%) HER2-negative, and 15,272 (14.6%) HER2-positive. The breast cancer as primary malignancy was observed in 84,944 (81.16%) patients. In primary malignant breast cancer (PMBC) patients, the hazard ratio among HER2-negative patients was significantly higher than HER2-positive patient samples (HR = 0.772, 95% CI 0.715-0.833, p = < .001), whereas HER2 negative status was not significantly favorable in PMBC negative patients in HER2-positive (HR = .919, 95% 0.797-1.06, p = .248). Most importantly in PMBC patients, the HR for HER2-borderline was poor in comparison to HER2 negative (HR = 1.354, 95% CI 1.126-1.627, p = < .001). Conclusion This is the first report with large cohort of patient samples and significant statistical power to demonstrate that HER2 borderline represents a negative prognostic factor for PMBC. Thus providing rationale for controlled clinical trial for HER2-targeted therapies in HER2-borderline patients.