Principal Investigator: Lewis Chodosh, MD, PhD (University of Pennsylvania)

The Science: While animal models currently used to study BRCA-related cancers help to propel many research advances, they do not fully mimic BRCA biology and disease progression as it occurs in humans. 

This project aims to create new, more faithful animal models, particularly focused on recreating the effects of pregnancy on breast cancer risk. 

The Hope: These models would give researchers a powerful new platform to study the biology of BRCA mutations and their impact on cancer development. Such models would be especially useful as mimicking pregnancy-induced protection represents a potential approach to intercepting breast cancer development in BRCA mutation carriers.

Principal Investigator: Christine Edmonds, MD (University of Pennsylvania)

The Science: While BRCA1 is well known for its role in DNA repair, recent research shows it may also help cells manage energy, process fats, and protect themselves from harmful molecules — all of which could influence breast cancer development. This project builds on these discoveries by testing a new metabolic imaging technology in a pilot study, exploring its potential as a tool for early detection of breast cancer in people with BRCA1 mutations.

The Hope: This study could improve our understanding of how metabolism changes in BRCA1-related breast cancer and may lead to more accurate screening methods, helping detect cancer earlier when treatment is most effective.

Principal Investigators: Bryson Katona, MD, PhD and Sydney Shaffer, MD, PhD (University of Pennsylvania)

The Science: Recent research suggests that BRCA1/2 mutation carriers may be at an increased risk of gastric cancer, however, additional study is needed to fully understand this association. This project will identify the differences in the stomach lining of BRCA mutation carriers, as well as study the changes that lead to cancer formation. 

The Hope: By using a novel approach, researchers hope to learn more about the dynamics that predispose mutation carriers to cancer and uncover actionable targets for gastric cancer interception. 

Principal Investigators: Kara Maxwell, MD, PhD and Sydney Shaffer, MD, PhD (University of Pennsylvania)

The Science: In men who carry a BRCA2 mutation, losing the “backup” healthy copy of the gene is thought to trigger prostate cancer growth. But scientists still don’t fully understand how this loss actually leads to cancer. To explore this, the team is studying a large collection of prostate tissue samples from Penn Medicine and the VA.

The Hope: A deeper understanding of the processes behind prostate cancer development will lead to more precision treatment options and the discovery of potential targets to intercept BRCA-related prostate cancer at its earliest stages. 

Principal Investigators: Bruno Barufaldi, PhD and Anne Marie McCarthy, ScM, PhD (University of Pennsylvania)

The Science: Current breast cancer risk models primarily rely on imaging, genetic, or clinical data analyses, often using methods that fail to capture the complex interplay of these data. This fragmented approach limits the ability to provide personalized risk estimates for each woman. 

This project aims to unify these disparate data sources into a single multi-modal AI framework, improving the precision of risk predictions. 

The Hope: The goal is to enable dynamic, personalized AI breast cancer risk assessment to help equip patients with timely and accurate risk information to better determine whether and when prophylactic procedures and intensive screenings are most beneficial. 

Principal Investigators: Michiel Simons, MD, PhD (Radboud University Medical Center, Nijmegen, The Netherlands)

The Science: Serous tubal intraepithelial carcinoma (STIC) lesions are a precursor to ovarian cancer and are identified in 3-8% of women who undergo risk-reducing surgery. Prior research by Dr. Simons and their team has shown that supporting pathologist’s diagnostics with AI improves their ability to diagnose STIC. This project aims to expand the existing STIC detection AI model to detect fallopian tube cancers and to evaluate the full model’s performance in a clinical cohort. 

Principal Investigator: Iain McNeish (Imperial College, London)

The Science: Isolated pre-invasive serous tubal epithelial carcinoma (STIC) lesions are identified in 3–8% of women with BRCA mutations undergoing risk-reducing surgery for ovarian cancer. There is a significant risk of secondary advanced high grade serous cancer (HGSC) in women with isolated STIC lesions. This project will use whole genome sequencing and advanced imaging to compare the features of a rare group of STIC lesion that progresses to HGSC to a group that did not. 

The Hope: Researchers hope this work will help improve risk stratification for those undergoing risk-reducing surgery, potentially identifying those who require chemotherapy after surgery to prevent recurrence. 

Principal Investigator: Nur Yucer, PhD (University of Texas Health San Antonio)

The Science: While PARP inhibitors have transformed treatment of BRCA-related prostate cancer, there is still a subset of patients who do not respond to this treatment. This project aims to study the differences between BRCA2-related prostate cancer using a new technique that combines 3D models of prostate cancer with CRISPR and RNA gene sequencing.