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. 2012 Jun 15;18(12):3462-9.
doi: 10.1158/1078-0432.CCR-11-2696. Epub 2012 Mar 15.

Detection of tumor PIK3CA status in metastatic breast cancer using peripheral blood

Michaela J Higgins  1 , Danijela Jelovac, Evan Barnathan, Brian Blair, Shannon Slater, Penny Powers, Jane Zorzi, Stacie C Jeter, George R Oliver, John Fetting, Leisha Emens, Carol Riley, Vered Stearns, Frank Diehl, Philipp Angenendt, Peng Huang, Leslie Cope, Pedram Argani, Kathleen M Murphy, Kurtis E Bachman, Joel Greshock, Antonio C Wolff, Ben H Park
Affiliations

Detection of tumor PIK3CA status in metastatic breast cancer using peripheral blood

Michaela J Higgins et al. Clin Cancer Res. .

Abstract

Purpose: We sought to evaluate the feasibility of detecting PIK3CA mutations in circulating tumor DNA (ctDNA) from plasma of patients with metastatic breast cancer using a novel technique called BEAMing.

Experimental design: In a retrospective analysis, 49 tumor and temporally matched plasma samples from patients with breast cancer were screened for PIK3CA mutations by BEAMing. We then prospectively screened the ctDNA of 60 patients with metastatic breast cancer for PIK3CA mutations by BEAMing and compared the findings with results obtained by screening corresponding archival tumor tissue DNA using both sequencing and BEAMing.

Results: The overall frequency of PIK3CA mutations by BEAMing was similar in both patient cohorts (29% and 28.3%, respectively). In the retrospective cohort, the concordance of PIK3CA mutation status by BEAMing between formalin-fixed, paraffin-embedded (FFPE) samples and ctDNA from temporally matched plasma was 100% (34 of 34). In the prospective cohort, the concordance rate among 51 evaluable cases was 72.5% between BEAMing of ctDNA and sequencing of archival tumor tissue DNA. When the same archival tissue DNA was screened by both sequencing and BEAMing for PIK3CA mutations (n = 41 tissue samples), there was 100% concordance in the obtained results.

Conclusions: Analysis of plasma-derived ctDNA for the detection of PIK3CA mutations in patients with metastatic breast cancer is feasible. Our results suggest that PIK3CA mutational status can change upon disease recurrence, emphasizing the importance of reassessing PIK3CA status on contemporary (not archival) biospecimens. These results have implications for the development of predictive biomarkers of response to targeted therapies.

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Conflict of interest statement

Disclosure of Potential Conflicts of Interest

F. Diehl and P. Angenendt are employees and stakeholders of Inostics GmBH who conducted BEAMing analyses. K.E. Bachman and J. Greshock are employees of GlaxoSmithKline. L.A. Emens has a commercial research grant for Genentech Incorporation and is a consultant/advisory board member for Genentech Incorporation, Bristol Myers Squibb, and Roche. B.H. Park is a consultant/advisory board member for GlaxoSmithKline and Horizon Discovery, Ltd. No potential conflicts of interest were disclosed by the other authors.

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