Ki67 expression and the effect of neo-adjuvant chemotherapy on luminal HER2-negative breast cancer.
Ki67 expression and the effect of neo-adjuvant chemotherapy on luminal HER2-negative breast cancer.
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DOI：
10.1186/1471-2407-14-550
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发表时间：
2014-07-30
期刊：
影响因子：
3.8
通讯作者：
Saito M
中科院分区：
文献类型：
--
作者：
Horimoto Y;Arakawa A;Tanabe M;Sonoue H;Igari F;Senuma K;Tokuda E;Shimizu H;Kosaka T;Saito M
腔HER 2阴性肿瘤患者预后良好。然而，有一个亚群，其中获得较差的结果与内分泌治疗单独。认为该亚群可从化疗中获益。然而，由于最近治疗策略的变化，化疗对管腔肿瘤患者的重要性已经降低。因此，在临床实践中，我们通常很难确定是否应该向此类患者推荐化疗。我们研究了Ki 67表达，作为预测管腔HER 2阴性乳腺癌患者对新辅助化疗（NAC）的反应的一种手段，以确定将从这些治疗中受益的亚群。我们入组了114例在NAC后接受手术的管腔型HER 2阴性乳腺癌患者。使用治疗前获得的活检标本检查生物标志物，以避免任何化疗相关影响。化疗效果采用手术标本确定，我们定义的病理完全反应（pCR）为侵入性巢消失，仅基于原发性乳腺肿瘤。我们对114例患者的数据进行了受试者工作特征曲线分析，以研究Ki 67表达作为pCR的预测因子。Ki 67高表达的肿瘤的pCR率显著较高（p < 0.01），所有获得pCR的患者在中位58个月的观察期内保持无复发。我们将35%确定为Ki 67临界值，该临界值将pCR患者与其他病例区分开来。另一个数据集，包括196名患者，中位观察期为29个月，被招募进行验证。发现Ki 67表达高于35%的肿瘤患者的无病生存率显著（p < 0.01）较低。我们的研究结果提高了Ki 67表达高于35%的管腔HER 2阴性亚群从化疗中获益的可能性，如生存率改善所证明的。本文的在线版本（doi：10.1186/1471-2407-14-550）包含补充材料，可供授权用户使用。
Patients with luminal HER2-negative tumours have a favourable prognosis. However, there is a subpopulation in which poorer outcomes are obtained with endocrine therapy alone. This subpopulation is considered to benefit from chemotherapy. However, the significance of chemotherapy for those with luminal tumours has decreased due to recent changes in treatment strategies. Thus, it is often difficult to determine whether we should recommend chemotherapy to such patients in clinical practice. We investigated Ki67 expression, as a means of predicting the responses of luminal HER2-negative breast cancer patients to neo-adjuvant chemotherapy (NAC), in order to identify a subpopulation that would benefit from these treatments. We enrolled 114 luminal HER2-negative breast cancer patients undergoing surgery after NAC. Biomarkers were examined using biopsy specimens obtained prior to treatment, to avoid any chemotherapy-related effects. Chemotherapy effects were determined employing operative specimens and we defined pathological complete response (pCR) as invasive nest disappearance, based only on the primary breast tumour. We applied receiver operating characteristic curve analysis to data from our 114 patients, to investigate Ki67 expression as a predictor of pCR. The pCR rate was significantly higher for tumours with high Ki67 expression (p < 0.01) and all patients who obtained pCR remained recurrence-free during the median 58-month observation period. We identified 35% as the Ki67 cut-off value which distinguishes those with a pCR from other cases. Another dataset, comprised of 196 patients with a median 29-month observation period, was recruited for validation. Disease-free survival was found to be significantly (p < 0.01) lower in the patients with tumours in which Ki67 expression was higher than 35%. Our results raise the possibility of the luminal HER2-negative subpopulation with Ki67 expression higher than 35% benefiting from chemotherapy, as evidenced by improved survival. The online version of this article (doi:10.1186/1471-2407-14-550) contains supplementary material, which is available to authorized users.
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