Analysis of ESR1 and PIK3CA mutations in plasma cell-free DNA from ER-positive breast cancer patients

• Published in: Oncotarget Vol. 8; no. 32; pp. 52142 - 52155
• Main Authors: Takeshita, Takashi, Yamamoto, Yutaka, Yamamoto-Ibusuki, Mutsuko, Tomiguchi, Mai, Sueta, Aiko, Murakami, Keiichi, Omoto, Yoko, Iwase, Hirotaka
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 08.08.2017
• Subjects: Research Paper; ESR1 mutations; cell-free DNA; acquired endocrine therapy resistance; PIK3CA mutations; estrogen receptor-positive metastatic breast cancer
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.18479

The measurement of and mutations in plasma cell-free DNA (cfDNA) has been studied as a non-invasive method to quickly assess and monitor endocrine therapy (ET) resistant metastatic breast cancer (MBC) patients. The subjects of this retrospective study were a total of 185 plasma samples from 86 estrogen receptor-positive BC patients, of which 151 plasma samples were from 69 MBC patients and 34 plasma samples were from 17 primary BC (PBC) patients. We developed multiplex droplet digital PCR assays to verify the clinical significance of and mutations both in a snapshot and serially in these patients. cfDNA and mutations were found in 28.9% and 24.6 % of MBC patients, respectively. The relation between or mutations and clinical features showed that mutations occurred mostly in patients previously treated by ET, which was not the case for mutations. The analysis of the clinical impact of those mutations on subsequent lines of treatment for the 69 MBC patients revealed that both and mutations detection were related to a shorter duration of ET effectiveness in univariate analysis but only for mutations in multivariate analysis. The monitoring of cfDNA in a subset of 52 patients showed that loss of mutations was related to a longer duration of response, which was not the case for mutations. We have demonstrated the clinical significance of on-treatment mutations both in a snapshot and serially in comparison with mutations.