Tibau Ariadna, López-Vilaró Laura, Pérez-Olabarria Maitane, Vázquez Tania, Pons Cristina, Gich Ignasi, Alonso Carmen, Ojeda Belén, Ramón y Cajal Teresa, Lerma Enrique, Barnadas Agustí, Escuin Daniel
Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain ; Institut d'Investigacions Biomèdiques Sant Pau, Barcelona, Spain.
Institut d'Investigacions Biomèdiques Sant Pau, Barcelona, Spain ; Department of Pathology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Neoplasia. 2014 Oct 23;16(10):861-7. doi: 10.1016/j.neo.2014.08.012. eCollection 2014 Oct.
Human epidermal growth factor receptor 2 (HER2) and topoisomerase II alpha (TOP2A) genes have been proposed as predictive biomarkers of sensitivity to anthracycline chemotherapy. Recently, chromosome 17 centromere enumeration probe (CEP17) duplication has also been associated with increased responsiveness to anthracyclines. However, reports are conflicting and none of these tumor markers can yet be considered a clinically reliable predictor of response to anthracyclines. We studied the association of TOP2A gene alterations, HER2 gene amplification, and CEP17 duplication with response to anthracycline-based neoadjuvant chemotherapy in 140 patients with operable or locally advanced breast cancer. HER2 was tested by fluorescence in situ hybridization and TOP2A and CEP17 by chromogenic in situ hybridization. Thirteen patients (9.3%) achieved pathologic complete response (pCR). HER2 amplification was present in 24 (17.5%) of the tumors. TOP2A amplification occurred in seven tumors (5.1%). CEP17 duplication was detected in 13 patients (9.5%). CEP17 duplication correlated with a higher rate of pCR [odds ratio (OR) 6.55, 95% confidence interval (95% CI) 1.25-34.29, P = .026], and analysis of TOP2A amplification showed a trend bordering on statistical significance (OR 6.97, 95% CI 0.96-50.12, P = .054). TOP2A amplification and CEP17 duplication combined were strongly associated with pCR (OR 6.71, 95% CI 1.66-27.01, P = .007). HER2 amplification did not correlate with pCR. Our results suggest that CEP17 duplication predicts pCR to primary anthracycline-based chemotherapy. CEP17 duplication, TOP2A amplifications, and HER2 amplifications were not associated with prognosis.
人表皮生长因子受体2（HER2）和拓扑异构酶IIα（TOP2A）基因已被提出作为蒽环类化疗敏感性的预测生物标志物。最近，17号染色体着丝粒计数探针（CEP17）重复也与对蒽环类药物反应性增加有关。然而，报道相互矛盾，这些肿瘤标志物中尚无一种可被视为对蒽环类药物反应的临床可靠预测指标。我们研究了TOP2A基因改变、HER2基因扩增和CEP17重复与140例可手术或局部晚期乳腺癌患者对蒽环类新辅助化疗反应之间的关联。通过荧光原位杂交检测HER2，通过显色原位杂交检测TOP2A和CEP17。13例患者（9.3%）达到病理完全缓解（pCR）。24例（17.5%）肿瘤存在HER2扩增。7例肿瘤（5.1%）发生TOP2A扩增。13例患者（9.5%）检测到CEP17重复。CEP17重复与较高的pCR率相关[比值比（OR）6.55，95%置信区间（95%CI）1.25 - 34.29，P = 0.026]，TOP2A扩增分析显示有接近统计学意义的趋势（OR 6.97，95%CI 0.96 - 50.12，P = 0.054）。TOP2A扩增和CEP17重复联合与pCR密切相关（OR 6.71，95%CI 1.66 - 27.01，P = 0.007）。HER2扩增与pCR无关。我们的结果表明，CEP17重复可预测对以蒽环类为主的原发性化疗的pCR。CEP17重复、TOP2A扩增和HER2扩增与预后无关。
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