Background: Gene mutations in the PI3K pathway in breast tumors are associated with resistance to tamoxifen and poorer prognosis. Differences in host susceptibility to developing breast cancers with PI3K pathway mutations may explain the heterogeneity in response to tamoxifen for chemoprevention and breast cancer outcomes. The objective of the study was to evaluate the association between host germline single nucleotide polymorphisms (SNPs) and activation of the PI3K pathway in breast tumors.

Methods: We extracted tumor and germline DNA from 386 women with stages I-II breast cancer treated at the MD Anderson Cancer Center. Nine PI3K mutation sites were evaluated using the Sequenom assay and 57 tagging single nucleotide polymorphisms (SNPs) of candidate genes in the PI3K pathway were genotyped using the Illumina Golden Gate Platform.

Results: 36 patients (10%) had at least one mutation in the PI3K pathway. There was no association between PI3K mutation status by age at diagnosis or ethnicity. In univariate analysis, there was a statistically significant association between PI3K gene mutation status and 3 tagging SNPs in the genes, PTEN (rs123421, rs1234213) and IGF-1 (rs2033178).

Conclusion: PI3K mutations are rare in breast tumors but represent a druggable target for prevention and treatment. Host genetics may play a role in contributing to tumor biology and serve to identify individuals at risk for tumors with PI3K pathway activation and tamoxifen resistance.

Citation Format: Abenaa M. Brewster, Melissa Bondy, Kim-anh Do, Aysegul Sahin, Katherine Hale, Caimiao Wei, Gordon Mills, Patricia Thompson. The association between germline genetic variants in the PI3K pathway and PI3K mutations in breast tumors. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr B84.