Judith Balmaña, MD, PhD

Titles and Affiliations

Head of the Hereditary Cancer Genetics Group
Clinical Research Program

Research area

Testing innovative approaches for routine genetic counseling to tailor prevention and early detection strategies for individuals at variable risk of developing breast and ovarian cancer.

Impact

The current clinical approach for assessing breast and ovarian cancer risk relies on the evaluation of family history and performing genetic testing to detect pathogenic variants in genes associated with breast and ovarian cancer. However, there are additional genetic variants associated with disease susceptibility that are not captured by common tests. This wider genetic variation may modify the average risk attributed to carriers of pathogenic variants and may also explain the “currently unknown” genetic susceptibility in people who do not carry these variants. Polygenic risk scores (PRS) are a composite of common genetic variation that can be used to refine a person’s susceptibility to diseases that cannot be solely explained by pathogenic variants, thus personalizing hereditary cancer risk assessment. Previous work by Dr. Balmaña’s group using gene panel testing and genotyping arrays has demonstrated the potential of applying PRS for expanding risk assessment of breast and ovarian cancer in healthy individuals.

Progress Thus Far

Dr. Balmaña and her team are focusing on implementing a predictive breast cancer risk model called BOADICEA V6, which incorporates polygenic risk scores (PRS), carrier status of pathogenic variants, and non-genetic factors, including breast density. She and her team conducted a pilot study of 20 participants, all of whom consented to whole genome sequencing (WGS) and to receiving secondary findings, including those associated with other cancers and non-cancerous conditions such as cardiovascular disease. The team calculated personalized breast cancer risk scores obtained from WGS and compared the results with routine panel testing. Then, they evaluated the impact of incorporating PRS and breast mammographic density in 240 unaffected women who are carriers of a pathogenic variant in the genes PALB2, ATM, CHEK2, RAD51C, RAD51D, or BARD1. This led to a change in 10-year risk category in 26 percent of the cases, supporting the role of including PRS and breast density in refining breast cancer risk estimates.

What’s next

Over the coming year, Dr. Balmaña and her team will continue to work on evaluating PRS to improve personalized breast and ovarian cancer risk prediction. The team will recruit more participants with clinical suspicion of hereditary breast and ovarian cancer (HBOC) as well as those undergoing single gene testing for WGS. To further examine the analytical utility of WGS, the team will compare its performance with their previous genotyping platform for low-risk variants included in the polygenic assessment. They also plan to obtain ovarian cancer PRS from WGS data and calculate personalized estimations of ovarian cancer. In parallel, Dr. Balmaña and her team are designing a digital tool to enhance patients’ understanding of HBOC genomic information, offer personalized risk, support their needs, and facilitate genetic testing in relatives of carriers of a pathogenic variant.

Biography

Judith Balmaña is the Head of the Hereditary Cancer Genetics Group at Vall d’Hebron Institute of Oncology (VHIO). In 2005, she established the Familial Cancer Program in the Medical Oncology Department at Hospital Vall d’Hebron (HVH). Since then, she has been leading this program and serving as an Attending Physician in the Breast Cancer Unit. She obtained her PhD in Medicine in 2009 from Universitat Autònoma de Barcelona and completed her residency in medical oncology at the Hospital Sant Pau, Barcelona, Spain.

She is a Professor at the Faculty of Medicine in the International University of Catalonia, and the hereditary cancer track coordinator of the Master in Genetic Counseling (UAB). She has actively been working in national and international hereditary breast cancer guidelines, including SEOM, ESMO, ASCO and ACMG (American College of Medical Genetics). Dr. Balmaña is the chair of the Hereditary Breast Cancer Thematic Group within the European Reference Network in Genetic Tumor Risk (ERN-GENTURIS) since 2017, co-chair of the ESMO Preceptorship in Hereditary Cancer since 2019, and member of the international research consortium CIMBA. She is also a member of the SOLTI’s Cooperative Group in breast cancer.

Dr. Balmaña is interested in unraveling the challenges of implementing the scientific advances in hereditary cancer susceptibility to clinical practice. She is proactively working on implementing the gene panels for hereditary cancer, a personalized breast cancer risk estimation and surveillance, and delineating the professional framework to provide an adequate genetic counseling process for individuals undergoing genetic testing.

Her clinical research group is currently investigating methods to implement analysis of polygenic risk to breast and ovarian cancer and its clinical impact on risk-based surveillance and prevention.