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

The Science: Breast cancer recurrence is a major concern for early-stage BRCA-related breast cancer patients. This research aims to study the biology of residual tumor cells (RTC), which give rise to recurrent tumors. It will also study the role of BRCA on tumor cell dormancy and recurrence. 

The Hope: This research aims to uncover unique vulnerabilities in BRCA-mutant RTCs that can be targeted and eliminated before they lead to a cancer recurrence. This represents a promising strategy for preventing cancer recurrence in  patients with BRCA-related breast cancer. 

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: 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.