Abstract P2-06-12: HER2 mRNA Expression Is Influenced by Estrogen Receptor Status and PI3K Mutational Status

Molecular profiling has suggested that ER+/HER2+ breast cancer is a distinct entity from ER-/HER2+ breast cancer and confers a worse prognosis in systemically untreated patients. It has recently been reported that genes associated with PI3K/AKT pathway activation predict pathologic complete response in patients receiving trastuzumab-chemotherapy in ER+/HER+ but not in ER-/HER2+ tumors. Past studies have indicated that 30-40% of breast cancers harbor a PI3K mutation, predominantly in exons 9 and 20. We analyzed 100 HER2+ breast cancers stratified by ER status to confirm the differing level of HER2 mRNA expression relative to ER status and to determine the association, in any, to the presence of a PI3K mutation. Methods: Fifty ER+ and 50 ER-breast cancers previously assessed as HER2+ (HER2:CEP-17 ratio ranging from 2.40-16.20, PathVysion Kit, Abbott) were pulled from the archives. ER was assessed by IHC, (6F11, NovaCastra) using a clinically validated method in accordance with the new CAP/ASCO guidelines. Molecular analysis was performed on paraffin embedded tissues. Tumor areas of interest were identified and selectively removed from the section. RNA and DNA were isolated from the collected tissue. Real-time quantitative RT-PCR was used to evaluate the expression of the HER2 gene from the RNA fraction. The expression values were calculated as a ratio of HER2 to the reference gene. The DNA was added to an allele specific PCR to assess 7 of the most common mutations in exons 9 and 20 of the PI3K gene. All data was generated on an AB 7900 HT real-time platform. Results: Quantitative HER2 mRNA Results Discusssion: The level of HER2 mRNA expression differs significantly based on the expression of ER. This is further accentuated by the presence of a PI3K mutation, increasing the level of HER2 mRNA expression is ER-patients and decreasing the level of HER2 mRNA expression in ER+ patients. This observation needs to be further explored and may have profound implications, if as current data suggests, the subset of patients most responsive to trastuzumab therapy are the ER+, PI3K activated tumors. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-06-12.