Mutations Identified Distinguishing Metastatic from Early-Stage HR+/HER2- Breast Cancer
New research may help identify new candidate targets and stratify patients eligible for innovative therapies.
|The following article features coverage from the San Antonio Breast Cancer Symposium (SABCS) 2018 meeting. Click here to read more of Cancer Therapy Advisor's conference coverage.|
Use of whole exome sequencing of metastatic breast cancers has identified 11 driver gene alterations and 4 mutational processes enriched in hormone receptor-positive/HER2-negative metastatic breast cancers.1
Fabrice Andre, of the Institut Gustave Roussy in France, who presented the results of the study at the 2018 San Antonio Breast Cancer Symposium in Texas, wrote that this additional information may help identify new candidate targets and stratify patients eligible for innovative therapies.
The research included patients with metastatic breast cancer and available biopsy as part of several precision medicine trials (SAFIR01, SAFIR02, PERMED, MOSCATO, SHIVA). The researchers performed sequencing on 387 patients with HR-positive/HER2-negative breast cancer, 186 patients with triple-negative breast cancer, and 32 patients with HER2-overexpressing breast cancers.
Among these patients, 24 driver genes were significantly mutated. In the patients with HR-positive/HER2-negative disease, 11 genes were found to be more frequently mutated in the metastatic setting compared with early-stage disease. These mutations included TP53 (29%), KMT2C (13%), NCOR1 (8%), NF1 (7%), RB1 (4%), C16orf3 (2%), FRG1 (6%), ESR1 (21%), RIC8A (4%), AKT1 (7%), and PLSCR5 (2%). No gene alterations were enriched in patient with metastatic HER2-overexpressing or triple-negative disease.
The majority of patients (73%) with HR-positive/HER2-negative metastatic disease had an actionable alteration compared with only 55% of patients with early-stage disease (P < .01).
The researchers also assessed mutational signatures to understand which mutational processes could drive cancer progression and found that in metastatic HR-positive/HER2-negative disease there was an increase in APOBEC, S3 (HRD), S10 (POLE-associated signature), and S17 signatures compared with early-stage disease.
Read more of Cancer Therapy Advisor's coverage of the SABCS 2018 meeting by visiting the conference page.
ReferenceAndre F, Filleron T, Ng C, et al. Genomic characterization of metastatic breast cancer. Oral presentation at the 2018 San Antonio Breast Cancer Symposium; December 4-8, 2018; San Antonion, TX. Abstract GS1-08.