Increased risk of endometrial cancer associated to mutations of the BRCA1 and BRCA2 genes

1 April 2021• NEWSITEM

Marthe de Jonge, a PhD student at the Leiden University Medical Centre (LUMC), is interested in exploring the genetic risks associated to endometrial cancer (EC). In a recent study, De Jonge and colleagues provide evidence that a correlation between increased EC risk and mutations in the breast cancer genes BRCA1 and BRCA2 (BRCA1/2) exists. The findings were published in the Journal of the National Cancer Insitute. De Jonge will defend her thesis “exploring the role of homologous recombination deficiency and BRCA1/2 mutations in endometrial cancer” after the summer.

Marthe de Jonge is a pathology resident and a PhD student of the Pathology Department. Her research focuses on the increased risk of EC and its relation to mutations in the breast cancer genes BRCA1/2.  In a recent study published by the Journal of the National Cancer Institute, De Jonge and colleagues provide the strongest evidence to date that women with certain BRCA1/2 mutations have, in fact, a higher risk of developing EC. She explains: “our findings are critical to the ongoing discussion of whether or not EC is a BRCA1/2-associated disease. Furthermore, understanding the genetic risks of EC pose unique opportunites for effective detection, and prevention”.&

Multicentre cohort study

According to De Jonge, many of the previous studies addressing EC risks among BRCA1/2 patients were limited due to various reasons, such as small sample sizes or insufficient follow-up data. “Due to our collaboration with the on-going Hereditary Breast and Ovarian Cancer – Netherlands (HEBON) multicenter cohort study, strengths of our analysis included a large sample size, high-quality data based on lengthy follow-ups and gave us the opportunity to perform pathology review”. 

Effective detection treatment and prevention

“Given the potential for BRCA1/2 mutations to generate carcinomas not only in the fallopian tube and ovary, but also of the endometrium, we believe genetic screening should be extended to women receiving certain EC diagnoses”, says De Jonge. This may detect new carriers and provide family members with the opportunity to decide about testing and, once finding out that they are carriers of the mutation as well, adequate counseling, prevention and screening. Moreover, women with EC in the context of BRCA1/2 mutations may benefit from treatment targeted at the BRCA1/2 mutation shown to be highly benefical in women suffering from BRCA1/2 related ovarian cancer. 

Finally, the increased risk should be considerd to be included in genetic counseling in order to raise awareness for the increased EC risk. By combining the study findings and her PhD research, she aims to gain further biological understanding of BRCA mutations and their association to EC: “In this way, we will be in a better place to derive evidence-based guidelines in the future”. 

Read the whole paper: Endometrial Cancer Risk in Women with Germline BRCA1 or BRCA2 Mutations: Multicenter Cohort Study.

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