Orlando Laura, Del Curto Barbara, Gandini Sara, Ghisini Raffaella, Pietri Elisabetta, Torrisi Rosalba, Balduzzi Alessandra, Cardillo Anna, Dellapasqua Silvia, Veronesi Paolo, Viale Giuseppe, Goldhirsch Aron, Colleoni Marco
Research Unit Medical Senology, European Institute of Oncology, Milan, Italy.
Breast. 2008 Oct;17(5):506-11. doi: 10.1016/j.breast.2008.03.007. Epub 2008 May 5.
Topoisomerase IIalpha (Topo II) is a potential marker of responsiveness to anthracycline-based therapy. We analyzed the role of Topo II gene status in the prediction of pathological complete remission (pCR) after primary anthracycline-based chemotherapy in non- endocrine responsive breast cancers overexpressing Her2/neu.
Twenty-three patients, with T2-T4, ER and PgR absent, overexpressing Her2/neu breast cancers treated with anthracycline-based chemotherapy were evaluated. Topo II gene status was assessed by FISH in pre-treatment tumor specimens and the results were correlated to pathological and clinical responses.
Overall, six patients had a pCR (26%). Topo II was amplified in 5 (22%) of the tumors. In all patients with Topo II amplification, Her2/neu gene amplification was also detected. Among patients without amplification, one had polysomia of chromosome (Cr) 17 and four patients had deletion of the Topo II gene. A higher probability of pCR was observed when Topo II amplification and Cr 17 polysomy were present: pCR was reported in 3 of 5 amplified tumors (60%), in the polysomic tumor (amplified plus polysomic 67%) and in only 2 out of 13 tumors without alteration of Topo II status (15%). If we compare the frequency of pCR in tumors with amplification or polysomy versus the frequency of tumors with not amplification (deletion or no modification), a significant difference was detected (p=0.02). One progressive disease (PD) was reported in one tumor with Topo II deletion (1/4, 25%) and one in tumor without any modification of Topo II gene status (1/13, 8%).
In patients with endocrine unresponsive and Her2 overexpressing tumors, Topo II amplification or the presence of chromosome 17 polysomy correlate with a significantly high probability of achieving pCR after neoadjuvant, anthracycline-based chemotherapy. Further prospective studies in order to more clearly define the predictive role of Topo II status in this subgroup of patients are warranted.
拓扑异构酶IIα（Topo II）是基于蒽环类药物治疗反应性的一个潜在标志物。我们分析了Topo II基因状态在预测过表达Her2/neu的非内分泌反应性乳腺癌接受以蒽环类药物为基础的原发性化疗后病理完全缓解（pCR）中的作用。
对23例T2 - T4期、雌激素受体（ER）和孕激素受体（PgR）缺失、过表达Her2/neu的乳腺癌患者进行以蒽环类药物为基础的化疗并进行评估。在治疗前的肿瘤标本中通过荧光原位杂交（FISH）评估Topo II基因状态，并将结果与病理和临床反应相关联。
总体而言，6例患者达到pCR（26%）。5例（22%）肿瘤中检测到Topo II扩增。在所有Topo II扩增的患者中，也检测到Her2/neu基因扩增。在无扩增的患者中，1例有17号染色体（Cr）多体性，4例有Topo II基因缺失。当存在Topo II扩增和Cr 17多体性时，观察到pCR的概率更高：5例扩增肿瘤中有3例（60%）报告达到pCR，多体性肿瘤（扩增加有多体性的为67%），而在13例Topo II状态无改变的肿瘤中只有2例（15%）达到pCR。如果我们比较有扩增或多体性的肿瘤中pCR的频率与无扩增（缺失或无改变）的肿瘤频率，检测到有显著差异（p = 0.02）。在1例Topo II缺失的肿瘤中报告有1例疾病进展（PD）（1/4，25%），在1例Topo II基因状态无任何改变的肿瘤中有1例疾病进展（1/13，8%）。
在内分泌无反应且Her2过表达的肿瘤患者中，Topo II扩增或17号染色体多体性的存在与新辅助蒽环类药物化疗后达到pCR的显著高概率相关。有必要进行进一步的前瞻性研究，以便更清楚地确定Topo II状态在该亚组患者中的预测作用。
