Abstract 1583: Clinical significance of PIK3CA, AKT1, and ESR1 mutation in plasma cell-free DNA from estrogen receptor-positive breast cancer patients

Abstract

Abstract Background: In endocrine therapy (ET) resistance mechanisms, PI3K / AKT pathway abnormality and ESR1 mutation are drawing attention. In recent large-scale clinical trials, it was revealed that identification of these genetic abnormalities in cell-free DNA (cfDNA) was useful for rapid assessment and monitoring of the therapeutic effect in ET-resistant breast cancer (BC). However, the frequency of them per treatment line and its clinical significance have not been verified. Here we studied the clinical significance of PIK3CA, AKT1, and ESR1 mutation according to the treatment line in estrogen receptor (ER)-positive BC. METHODS: From 2003 to 2017, a total of 251 plasma specimens were collected from 128 patients with ER positive BC treated at our hospital. The breakdown were 133 plasma samples from 73 primary BC (PBC) patients and 118 plasma samples from 68 metastatic BC (MBC) patients. CfDNA was extracted from 500 μL of plasma. The hotspot of PIK3CA, AKT1, and ESR1 mutation in plasma cfDNA was verified using multiplex digital PCR method. RESULTS: In the PBC patient group, PIK3CA mutation was recognized at 15.1%, AKT1 mutation at 1.4%, and ESR1 mutation at 2.7%. The presence or absence of PIK3CA mutation did not affect clinical outcome. In the MBC patient group, the frequency of PIK3CA mutation increased from 16% to 32% and that of ESR1 mutation increased from 23% to 41.9% as the treatment line advanced. Furthermore, we examined the time to treatment failure (TTF) by dividing into early treatment line and late treatment line. In the early treatment group, patients with PIK3CA mutation had significantly shorter TTF (P = 0.035). However, the presence or absence of ESR1 mutation did not affect TTF. On the other hand, in the late treatment group, patients with ESR1 mutation had significantly shorter TTF (P = 0.048). However, the presence or absence of PIK3CA mutation did not affect TTF. Since AKT1 mutation was rare in both PBC patients and MBC patients, its clinical significance was unknown. CONCLUSION: We showed clinical significance of verification of PIK3CA, AKT1, and ESR1 mutation in cfDNA according to treatment line in ER positive BC patients. Citation Format: Takashi Takeshita, Mai Tomiguchi, Aiko Sueta, Mutsuko Yamamoto-Ibusuki, Yutaka Yamamoto, Hirotaka Iwase. Clinical significance of PIK3CA, AKT1, and ESR1 mutation in plasma cell-free DNA from estrogen receptor-positive breast cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1583.