Breast Center Zurich, Seefeldstrasse 214, 8008, Zurich, Switzerland.
Department for Gynecology and Obstetrics, Helios Hospital Wuppertal, University of Witten, Witten/Herdecke, Germany.
J Cancer Res Clin Oncol. 2019 Aug;145(8):2051-2059. doi: 10.1007/s00432-019-02968-2. Epub 2019 Jul 3.
Triple negative breast cancer (TNBC) harbors a heterogeneous group of carcinomas with poor prognosis and high genetic variability. As a potential aim for targeted therapy, genetic mutations leading to an activation of the phosphoinositide 3-kinase pathway in a catalytic subunit (PIK3CA) in breast cancer have been analyzed currently. Little is known about the clinical impact and prognostic or predictive value of this marker in TNBC subtypes.
Samples from 119 TNBC cases were submitted to immunohistochemical PIK3CA protein expression analysis and scored semi-quantitatively as negative, weak (1 +), or strongly expressed (2 +). Expression scores were correlated to patient's characteristics, imaging features, and TNBC subtypes. TNBC subtypes were categorized into four subtypes: basal like, mesenchymal like, luminal androgen receptor (LAR), and immunomodulatory.
We did not observe differences in clinical aspects and imaging features between TNBC with and without PIK3CA expression. PIK3CA expression was in general higher in the LAR subtype. The disease-free survival and overall survival were significantly better in TNBC with PIK3CA protein expression, independent of TNBC subtypes.
Despite conflicting results in the literature, our study clearly shows a better outcome of PIK3CA-expressing TNBC, independent of TNBC subtypes. PIK3CA expression in TNBC is not associated with specific clinical or diagnostic features. Further molecular studies and meta-analysis are warranted to clarify the prognostic and predictive role of PIK3CA protein expression.
三阴性乳腺癌(TNBC)是一组具有预后不良和高度遗传变异性的异质性癌。作为靶向治疗的潜在靶点,目前已经分析了导致乳腺癌中磷酸肌醇 3-激酶途径催化亚基(PIK3CA)激活的遗传突变。关于该标志物在 TNBC 亚型中的临床影响、预后或预测价值,人们知之甚少。
对 119 例 TNBC 病例的样本进行免疫组化 PIK3CA 蛋白表达分析,并进行半定量评分,结果分为阴性、弱阳性(1+)或强阳性(2+)。表达评分与患者特征、影像学特征和 TNBC 亚型相关联。将 TNBC 亚型分为四种亚型:基底样、间质样、腔面雄激素受体(LAR)和免疫调节型。
我们未观察到 PIK3CA 表达与无 PIK3CA 表达的 TNBC 在临床方面和影像学特征上存在差异。在 LAR 亚型中,PIK3CA 表达通常更高。PIK3CA 蛋白表达的 TNBC 无病生存率和总生存率明显更好,与 TNBC 亚型无关。
尽管文献中存在矛盾的结果,但我们的研究清楚地表明,PIK3CA 表达的 TNBC 具有更好的预后,与 TNBC 亚型无关。PIK3CA 在 TNBC 中的表达与特定的临床或诊断特征无关。需要进一步的分子研究和荟萃分析来阐明 PIK3CA 蛋白表达的预后和预测作用。