BRCA1/2 Mutations Raise Risk for Endometrial Cancer, Too

By Reuters Staff

April 02, 2021

NEW YORK (Reuters Health) - Women with a BRCA1 or BRCA2 mutation have an increased risk for endometrial cancer (EC), and the greatest risk is for the rare subgroup of serous-like and p53-abnormal endometrial cancers in BRCA1 mutation carriers, according to a Dutch study.

This study, say researchers, "adds critical evidence to the ongoing discussion whether or not EC is a BRCA1/2-associated disease, and further supports the mounting evidence that at least serous-like and p53-abnormal EC should be considered to be an integral part of the BRCA1/2-associated hereditary breast and ovarian cancer (HBOC) syndrome."

Women with a pathogenic germline mutation in the BRCA1 and BRCA2 breast-cancer genes have an increased risk for developing breast cancer, but whether BRCA1/2 mutations also increase a woman's lifetime risk for EC is unclear.

To investigate, Dr. Cor D. de Kroon of Leiden University Medical Center and colleagues studied nearly 6,000 BRCA1/2-mutation carriers, including 3,788 BRCA1-mutation carriers, 2,151 germline BRCA2-mutation carriers and 41 with both BRCA1 and BRCA2 mutations. They also studied 8,451 non-BRCA1/2-mutation carriers.

During roughly 22 years of follow-up, 58 BRCA1/2- and 33 non-BRCA1/2-mutation carriers developed EC.

BRCA1 and BRCA2 mutation carriers had a significant two- to three-fold increase in EC risk, with the highest risk increases found for two EC subgroups with "unfavorable" clinical outcomes: serous-like histology (8-10 fold) and p53-abnormal EC (11-12 fold), the researchers report in the Journal of the National Cancer Institute.

The increased risk cannot be fully explained by previous hormone therapy (HT) use and is therefore most likely causally associated with germline BRCA1/2 mutations, they note.

"Our results provide important additional information with regard to EC risks, that is essential for adequate genetic counseling of BRCA1/2 mutation carriers," they write.

"Despite the observed increased overall EC risks in BRCA1/2 mutation carriers, the cumulative overall EC risk (3.0%) and risk for EC of serous-like histology (1.1%) by 75 years remains low, as the life-time risk of developing EC is low in the general population," they add.

Given these observations, they say the "potential hazards and possible benefits of risk-reducing hysterectomy need to be carefully weighed, and shared decision making is crucial in order to conclude about an individually-tailored treatment advice with regard to risk-reducing surgery BRCA1/2 mutation carriers."

The study had no commercial funding and the authors have no relevant disclosures.

Dr. de Kroon did not respond to a request for comment by press time.

SOURCE: https://bit.ly/39rom01 Journal of the National Cancer Institute, online March 21, 2021.

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