Identification of germline variants to predict breast cancer subtype risk and outcome
Through several large national and international studies, including those within BCAC, we aim to identify germline variants that influence the development of breast cancer subtypes and variants that affect prognosis through treatment response and other mechanisms. To translate these insights into clinical benefit, we work collaboratively to integrate germline and tumour genetic variants, as well as molecular tumour markers, into (online) prediction models. For instance, we contribute to improve outcome prediction tools such as PREDICT, helping to refine individualized treatment and follow-up decisions for breast cancer patients, We manage several large data resources for this work including those of the BCAC and B-CAST.
We are active members of the Breast Cancer Association Consortium (BCAC), which has identified many novel breast cancer susceptibility loci. Our group maintains the BCAC clinico-pathological database, which includes detailed tumour characteristics, clinical diagnostics, treatment information, and follow-up data from more than 70 studies comprising over 110,000 patients.
Understanding and predicting risk of contralateral breast cancer
Contralateral breast cancer, a new primary tumour in the opposite breast, is a relatively rare event, with a 10-year cumulative incidence of around 4%, but it can be associated with poor outcomes. Improved risk prediction and a better understanding of the disease’s aetiology are essential to identify women at high or low risk of developing contralateral breast cancer, thereby optimizing the decision-making regarding contralateral preventive mastectomy and personalized follow up strategies.
To this end, we developed and validated the PredictCBC risk prediction model, using data from multiple studies that include patient, genetic, tumour, and treatment information. We are expanding the model with additional informative factors, such as a polygenic risk score, treatment for the first breast cancer, and breast features to improve its accuracy and clinical usefulness.
Familial breast cancer and ovarian cancer
Hebon
Early detection of cancer
Marjanka Schmidt, in addition to her role as group leader at the NKI, is theme leader of the research theme Early detection.
In collaboration with the AVL Centre for Early Detection, the Netherlands Cancer Institute provides the infrastructure to develop and test novel methods and to integrate successful innovations into clinical practice, aiming for earlier diagnosis, less invasive treatment and better outcomes.
Ethical legal and societal issues (ELSI)
We have made significant contributions toward improving consent and information procedures for the (secondary) use of residual tissue, images, and data in scientific research. Although most patients support the use of their materials and data, our studies revealed that they desire greater transparency regarding how these are used. In response to evolving societal norms and increasing demands, the Netherlands Cancer Institute implemented, in mid-2018, a new consent procedure informing all patients about potential research use and actively seeking their consent.
To further support responsible research practices, our national ELSI servicedesk provides information and advice on ethical, legal, and social issues in precision medicine and health research. We also conduct applied research projects on topics such as informed consent, patient communication, return of results, big and genomic data, and legal aspects of using patient materials and data for research.