Association between HER2, TOP2A, and response to anthracycline-based preoperative chemotherapy in high-risk primary breast cancer

Gottfried E Konecny, Giovanni Pauletti, Michael Untch, He-Jing Wang, Volker Möbus, Walther Kuhn, Christoph Thomssen, Nadia Harbeck, Ling Wang, Sophia Apple, Fritz Jänicke, Dennis J Slamon
Breast Cancer Research and Treatment 2010, 120 (2): 481-9
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.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"