Alvaro Monteiro, PhD

Titles and Affiliations

Senior Member, Population Sciences Division
H. Lee Moffitt Cancer Center
Professor, Department of Oncologic Sciences
University of South Florida College of Medicine

Research area

Identifying and stratifying BRCA1 and BRCA2 gene variants that confer intermediate risk of developing breast cancer.

Impact

Women with family history of breast and ovarian cancer often undergo genetic testing for mutations in the BRCA1 and BRCA2 genes, which are known to significantly increase breast cancer risk. Carriers of pathogenic BRCA1 and BRCA2 gene variants are offered prevention options that include more frequent screenings and prophylactic surgery. There are, however, BRCA gene mutations (variants) of uncertain clinical significance, meaning that association with risk cannot currently be assessed. Carriers of these mutations have no actionable information and cannot benefit from established clinical recommendations. Recently, several mutations in BRCA genes have been identified as intermediate risk variants, meaning they confer a higher-than-average risk but not as high as pathogenic BRCA variants. Many remain categorized as variants of uncertain significance or are incorrectly classified as benign. Currently, it is unclear which BRCA gene variants belong to the intermediate risk category and no specific clinical recommendations exist for carriers. Dr. Monteiro’s objective is to formally define a new category of intermediate risk BRCA variants and delineate the spectrum of risk in variants of breast cancer susceptibility genes.

Progress Thus Far

Dr. Monteiro and his team assessed data for hundreds of BRCA1 and BRCA2 gene variants and found that several hundred of them fall into the intermediate risk category compared to high-risk variants. The team is now assessing these candidate intermediate risk variants to develop guidelines for selecting this category of risk. They also found BRCA gene variants that may be less pathogenic than previously thought. The reduced risks associated with these variants provide the foundation to shift the paradigm of inherited risk; Dr. Monteiro is leading discussion in the field about classifying inherited risk on a continuum (scale) rather than a binary no risk or high risk. Ultimately, this work will help realize the goal of providing personalized and optimized risk assessment and care.

What’s next

Next, Dr. Monteiro will conduct validation studies of intermediate risk variants using confirmed intermediate risk variants as reference standards to identify those that are clinically relevant. Lastly, Dr. Monteiro will initiate discussions with clinical consultants to develop the framework of clinical guidelines that improve risk-appropriate cancer prevention for carriers of intermediate risk BRCA1 and BRCA2 gene variants.

Biography

Alvaro Monteiro, PhD is a senior member in the Population Sciences Division at the Moffitt Cancer Center and a professor in the Department of Oncologic Sciences at the University of South Florida College of Medicine. He is the Scientific Director of the Molecular Genomics Shared Facility and directs the Laboratory of Cancer Genetics & Genomics. He earned his doctorate in biochemistry at the Federal University of Rio de Janeiro, Brazil and did postdoctoral work in molecular biology at the Rockefeller University. Before moving to Moffitt, he was an assistant professor at the Weill Medical College of Cornell University in New York City. The main theme of Dr. Monteiro’s laboratory is the integration of systems biology and genetics to explore the role of genetic variation in cancer predisposition, development, and treatment. He aims to understand how rare and common genetic variation impacts on signal transduction networks and its role in disease with a focus on breast cancer. The laboratory has pioneered functional assays for BRCA1 and contributed to the development of tools for clinical annotation of rare variants in BRCA1, BRCA2, PALB2 and CHEK2 in hereditary breast and ovarian cancer syndrome. The laboratory also has an interest in common genetic variation in cancer susceptibility loci and have played an active role in the NIH/NCI GAME-ON (Genetic Associations and Mechanisms in Oncology) consortium as a member of its Functional Working group. Dr. Monteiro participates in training of molecular epidemiologists specializing in cancer since 2014 as a faculty member in the AACR Workshop on Integrative Molecular Epidemiology.