Tomoko Shibayama1,2, Siew-Kee Low3, Makiko Ono4, Takayuki Kobayashi5, Kokoro Kobayashi5, Ippei Fukada5, Yoshinori Ito5, Takayuki Ueno5, Shinji Ohno5, Yusuke Nakamura3, Shunji Takahashi4. 1. Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, Tokyo, Japan. tomoko.shibayama@jfcr.or.jp. 2. Breast Oncology Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo, Japan. tomoko.shibayama@jfcr.or.jp. 3. Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, Tokyo, Japan. 4. Department of Medical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan. 5. Breast Oncology Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo, Japan.
Abstract
PURPOSE: In this study, we aim to investigate the mutation spectrum of circulating tumor DNA among hormone receptor-positive metastatic breast cancer (HR-MBC) patients using ultradeep targeted resequencing. In addition, we also evaluate the correlation of mutations detected from this study with progression-free survival (PFS). MATERIALS AND METHODS: A total of 56 HR-MBC patients were enrolled. Cell-free DNA (cfDNA) was extracted from plasma and sequenced by using Oncomine Breast cancer cfDNA assay in this study. RESULT: Concentration of cfDNA is correlated with a number of metastatic organs and serum CEA levels (Spearman's rank correlation p = 0.0018, p = 0.0015 respectively). Cases with high cfDNA levels (≥ 2.6 ng/μl of plasma) showed worse progression-free survival (PFS) and overall survival compared with cases with low cfDNA levels (p = 0.043 and 0.046, respectively). Among these patients, 29 patients (51.7%) have TP53 mutations, 12 patients (30.3%) have PIK3CA mutations, and 9 patients (16.0%) have ESR1 mutations. Acquisition of ESR1 mutation increased according to the lines of hormone therapy. In addition, patients with ESR1 mutation showed shorter PFS than those without mutation (log-rank p = 0.047). In the multivariate analysis, ESR1 mutation and cfDNA concentration were significant for PFS (p = 0.027 and 0.006, respectively). In conclusion, assessment of ESR1 mutation and cfDNA concentration could be useful in predicting prognosis for HR-MBCs.
PURPOSE: In this study, we aim to investigate the mutation spectrum of circulating tumor DNA among hormone receptor-positive metastatic breast cancer (HR-MBC) patients using ultradeep targeted resequencing. In addition, we also evaluate the correlation of mutations detected from this study with progression-free survival (PFS). MATERIALS AND METHODS: A total of 56 HR-MBCpatients were enrolled. Cell-free DNA (cfDNA) was extracted from plasma and sequenced by using OncomineBreast cancer cfDNA assay in this study. RESULT: Concentration of cfDNA is correlated with a number of metastatic organs and serum CEA levels (Spearman's rank correlation p = 0.0018, p = 0.0015 respectively). Cases with high cfDNA levels (≥ 2.6 ng/μl of plasma) showed worse progression-free survival (PFS) and overall survival compared with cases with low cfDNA levels (p = 0.043 and 0.046, respectively). Among these patients, 29 patients (51.7%) have TP53 mutations, 12 patients (30.3%) have PIK3CA mutations, and 9 patients (16.0%) have ESR1 mutations. Acquisition of ESR1 mutation increased according to the lines of hormone therapy. In addition, patients with ESR1 mutation showed shorter PFS than those without mutation (log-rank p = 0.047). In the multivariate analysis, ESR1 mutation and cfDNA concentration were significant for PFS (p = 0.027 and 0.006, respectively). In conclusion, assessment of ESR1 mutation and cfDNA concentration could be useful in predicting prognosis for HR-MBCs.
Authors: Georgios Nteliopoulos; Karen Page; Allison Hills; Karen Howarth; Warren Emmett; Emma Green; Luke J Martinson; Daniel Fernadez-Garcia; Robert Hastings; David S Guttery; Laura Kenny; Justin Stebbing; Susan Cleator; Farah Rehman; Kelly L T Gleason; Andrijac Sanela; Charlotte Ion; Amelia J Rushton; Nitzan Rosenfeld; R Charles Coombes; Jacqueline A Shaw Journal: Breast Cancer Res Treat Date: 2021-06-07 Impact factor: 4.872