Genetic predisposition to cancer – implications for selective screening


Session type:

Harry de Koning1
1Erasmus MC & Johns Hopkins Bloomberg School of Public Health, Rotterdam, The Netherlands


Nationwide screening programmes for cancer are often directed towards average risk women or men. Separate guidelines may exist for high-risk persons, but evidence is much more limited on effectiveness or cost-effectiveness for different high risk groups. Randomized controlled trials for these risk groups are limited, so pooling of data and/or modeling are crucial. In this lecture, the experiences for breast cancer will be illustrated, and if time allows for colorectal cancer screening.

It is recommended that BRCA1/2 mutation carriers are screened for breast cancer with Magnetic Resonance Imaging (MRI) because of their very high cancer risk and the high sensitivity of MRI in detecting invasive cancers. Clinical observations however, suggest important differences in natural history between BRCA1 and BRCA2 tumors, which may warrant distinctive screening guidelines.

I will show the results from 3 large international studies of BRCA1/2 mutation carriers using annual MRI and mammography. For both BRCA1 and BRCA2, separate natural history models were calibrated to the results of these studies and used to predict the impact of various screening protocols on both detection characteristics and mortality.

Our combined screening data and subsequent modeling show for BRCA1 mutation carriers little benefit of adding mammography to MRI screening before age 40. Mammography does contribute to the tumor detection in BRCA2 mutation carriers, also below age 40 and there are important clinical differences in natural history between the two risk groups. MRI screening is of paramount importance for mortality reduction in both BRCA1 and BRCA2 mutation carriers aged 25-60. More data are needed to define the optimal screening of BRCA1/2 mutation carriers above age 60 yrs.