PhD defence M.A.C. (Maartje) Schreurs

Below is a brief summary of the dissertation: 

As part of HEreditary Breast and Ovarian cancer study the Netherlands (Hebon) cohort, we identified women who were tested in one of the clinical genetic centers for the CHEK2 c.1100delC variant. In total, we have included 1374 heterozygotes, 24 homozygotes and 404 tested non-carriers. Using their information, we looked into breast cancer risk prediction, risks of other cancers within these families, and clinical outcomes.

First, we found that adding polygenic risk scores, lifestyle factors and breast density to family history and genetic status resulted in a broader range of lifetime breast cancer risk compared to only using family history and genetic status. Approximately one in three would be classified differently and should therefore be eligible for a different screening regimen. This could potentially help in personalized breast cancer risk estimations and optimizing surveillance strategies in CHEK2 c.1100delC women and non-carriers from CHEK2 families. Second, we studied the pedigrees from heterozygotes. Within these families, we found an increased risk of breast cancer, colorectal cancer and heamatological cancers in women. In men, we found a possible underreporting of cancer. Finally, we studied the clinical outcomes after breast cancer. While previous studies reported a significant worse survival, we did not find this in our Dutch cohort. Possible explanations for that include the later years of diagnosis (>2006) and the modern treatment regimens. However, further research is needed to validate these findings.