Association between HER2, TOP2A, and response to anthracycline-based preoperative chemotherapy in high-risk primary breast cancer
Document Type
Article
Publication Title
Breast Cancer Research and Treatment
Abstract
In breast cancer, recent studies suggest that the value of HER2 for predicting response to anthracyclinebased 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 nonamplified 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 HER2amplified 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.
First Page
481
Last Page
489
DOI
10.1007/s10549-010-0744-z
Publication Date
4-1-2010
Recommended Citation
Konecny, Gottfried E.; Pauletti, Giovanni; Untch, Michael; Wang, He Jing; Möbus, Volker; Kuhn, Walther; Thomssen, Christoph; Harbeck, Nadia; Wang, Ling; Apple, Sophia; Jänicke, Fritz; and Slamon, Dennis J., "Association between HER2, TOP2A, and response to anthracycline-based preoperative chemotherapy in high-risk primary breast cancer" (2010). Pharmaceutical and Administrative Sciences Faculty Publications. 170.
https://doi.org/10.1007/s10549-010-0744-z
https://collections.uhsp.edu/pharm-admin-sciences_pubs/170