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William J. Gradishar, MD, FACP, FASCO
William J. Gradishar, MD, FACP, FASCO
Posted: Thursday, November 3, 2022
Findings presented in the American Journal of Human Genetics demonstrated a characteristic genomic landscape in PTEN hamartoma tumor syndrome (PHTS) breast cancers, an entity that is currently treated similarly to sporadic breast cancers. These findings indicate a need for personalized strategies to treat this hereditary cancer predisposition syndrome, concluded Charis Eng, MD, PhD, of the Cleveland Clinic Lerner Research Institute, and colleagues. According to the investigators, this syndrome caused by germline mutations in PTEN increases the lifetime risk of breast cancer up to 85%, compared with 12% in the general population.
“Our findings reveal a distinct breast cancer biology in the context germline PTEN mutations that spotlights the need to develop more targeted, personalized strategies to effectively treat and, in time, prevent PHTS-associated breast cancers,” commented Dr. Eng in a Cleveland Clinic press release.
In this study, the authors performed and analyzed exome-sequencing data from 44 women with germline PTEN variants who developed breast cancer. A control cohort featured 497 women with sporadic breast cancers from The Cancer Genome Atlas data set.
The investigators found that PHTS-derived breast cancers had a distinct somatic mutational landscape when compared with sporadic counterparts. These unique PHTS-derived tumors had mainly second somatic hits in PTEN, distinct mutational signatures, and increased genomic instability.
Patients in the PHTS cohort had a significantly higher frequency of somatic PTEN variants compared with those in The Cancer Genome Atlas (22.7% vs. 5.6%, respectively). The PHTS group also had a lower mutational frequency in PIK3CA compared with somatic PTEN variants (22.7% vs. 33.4%). Somatic variants in PTEN and PIK3CA were mutually exclusive in PHTS, but that was not found to be the case in The Cancer Genome Atlas data set.
“As clinical genetic testing becomes more widely accessible, we undoubtedly will see a rise in the incidence of PHTS-associated breast cancer,” said Dr. Eng. “PHTS-associated breast cancers often develop at a younger age and may progress more aggressively than their sporadic counterparts....”
Disclosure: The study authors reported no conflicts of interests.
American Journal of Human Genetics
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