UCLA Translational Oncology Research Lab, David Geffen School of Medicine, University of California Los Angeles, 2825 Santa Monica Blvd, Suite 200, Santa Monica, CA, 90404-2429, USA.
Breast Cancer Res Treat. 2010 Apr;120(2):481-9. doi: 10.1007/s10549-010-0744-z. Epub 2010 Feb 4.
In breast cancer, recent studies suggest that the value of HER2 for predicting response to anthracycline-based chemotherapy may be more likely related to the concomitant amplification of the TOP2A gene. Here, we study the association between HER2 or TOP2A status and response to anthracycline-based preoperative chemotherapy and explore the interaction between HER2 or TOP2A status and intense dose-dense (IDD) chemotherapy. HER2 and TOP2A gene alterations were quantified by fluorescence in situ hybridization in primary tumor core biopsies from 373 high-risk primary breast cancer patients (tumors >/=3 cm or inflammatory) that received an IDD or conventionally scheduled anthracycline-based preoperative chemotherapy. HER2 was amplified in 94/350 tumors (27%) of which 40/94 (46%) demonstrated TOP2A amplification, and 17/94 (18%) TOP2A deletions. TOP2A gene alterations were not found in HER2 non-amplified cases. HER2 amplification was associated with a significantly higher pathologic complete response (pCR) rate only when TOP2A was co-amplified (30% vs. 11%, P = 0.002), but not when deleted (13% vs. 11%, P = 0.755), or normal (14% vs. 11%, P = 0.578) compared to HER2 non-amplified tumors. In multivariate analysis, TOP2A amplification (odds ratio [OR] 3.04, P = 0.021), but not HER2 amplification (OR 1.74, P = 0.170) was associated with a significantly higher pCR rate. No interaction was observed between HER2 or TOP2A status and IDD chemotherapy. TOP2A gene amplification may define a subset of HER2-amplified breast cancers that are responsible for the markedly improved chemosensitivity seen in HER2-positive breast cancer. However, added benefit of IDD chemotherapy itself was not associated with HER2 or TOP2A status.
在乳腺癌中，最近的研究表明，HER2 预测蒽环类药物为基础的化疗反应的价值可能与 TOP2A 基因的同时扩增更为相关。在这里，我们研究了 HER2 或 TOP2A 状态与蒽环类药物为基础的术前化疗反应之间的关系，并探讨了 HER2 或 TOP2A 状态与强化密集剂量（IDD）化疗之间的相互作用。在 373 例高危原发性乳腺癌患者（肿瘤>/=3 厘米或炎症）的原发性肿瘤核心活检中，通过荧光原位杂交定量检测 HER2 和 TOP2A 基因改变，这些患者接受了 IDD 或常规计划的蒽环类药物为基础的术前化疗。350 例肿瘤中有 94 例（27%）存在 HER2 扩增，其中 40/94 例（46%）存在 TOP2A 扩增，17/94 例（18%）存在 TOP2A 缺失。在 HER2 非扩增病例中未发现 TOP2A 基因改变。仅当 TOP2A 共扩增时，HER2 扩增与较高的病理完全缓解（pCR）率显著相关（30% vs. 11%，P = 0.002），而当 TOP2A 缺失（13% vs. 11%，P = 0.755）或正常（14% vs. 11%，P = 0.578）时则不相关。多变量分析显示，TOP2A 扩增（比值比[OR] 3.04，P = 0.021）而不是 HER2 扩增（OR 1.74，P = 0.170）与较高的 pCR 率显著相关。未观察到 HER2 或 TOP2A 状态与 IDD 化疗之间的相互作用。TOP2A 基因扩增可能定义了 HER2 扩增乳腺癌的一个亚组，这是 HER2 阳性乳腺癌化疗敏感性显著提高的原因。然而，IDD 化疗本身的额外益处与 HER2 或 TOP2A 状态无关。
