We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Genomic analysis of plasma circulating tumor DNA in patients with heavily pretreated HER2 + metastatic breast cancer.
- Authors
Lee, Kyoungmin; Lee, Jongwon; Choi, Jungmin; Sim, Sung Hoon; Kim, Jeong Eun; Kim, Min Hwan; Park, Yeon Hee; Kim, Jee Hyun; Koh, Su-Jin; Park, Kyong Hwa; Kang, Myoung Joo; Ahn, Mi Sun; Lee, Kyoung Eun; Kim, Hee-Jun; Ahn, Hee Kyung; Kim, Han Jo; Park, Keon Uk; Park, In Hae
- Abstract
We explored accumulated genomic alterations in patients with heavily treated HER2 + metastatic breast cancer enrolled in the KCSG BR18-14/KM10B trial. Targeted sequencing was performed with circulating tumor DNAs (ctDNAs) collected before the treatment of 92 patients. ctDNAs collected at the time of disease progression from seven patients who had a durable response for > 12 months were also analyzed. Sixty-five genes were identified as pathogenic alterations in 99 samples. The most frequently altered genes were TP53 (n = 48), PIKCA (n = 21) and ERBB3 (n = 19). TP53 and PIK3CA mutations were significantly related with shorter progression free survival (PFS), and patients with a higher ctDNA fraction showed a worse PFS. The frequency of homologous recombination deficiency (HRD)-related gene mutations was higher than that in matched tumor tissues, and these mutations tended to be associated with shorter PFS. New pathogenic variants were found at the end of treatment in all seven patients, including BRCA2, VHL, RAD50, RB1, BRIP1, ATM, FANCA, and PIK3CA mutations. In conclusion, TP53 and PIK3CA mutations, as well as a higher ctDNA fraction, were associated with worse PFS with trastuzumab and cytotoxic chemotherapy. The enrichment of HRD-related gene mutations and newly detected variants in ctDNA may be related to resistance to treatment.
- Subjects
CIRCULATING tumor DNA; METASTATIC breast cancer; GENOMICS; PROGRESSION-free survival; CANCER chemotherapy; GENETIC mutation
- Publication
Scientific Reports, 2023, Vol 13, Issue 1, p1
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/s41598-023-35925-8