Meet Our Researchers

Nikhil Wagle

Associate Member at the Broad Institute
Assistant Professor at Harvard Medical School
Deputy Director, Center for Cancer Precision Medicine, Dana-Farber Cancer Institute
The Question

Breast cancer is the leading cause of cancer-related deaths in women age 40 and younger, and survival rates for young women are lower than for older women, even though younger women usually receive more intensive therapy. Young women are more likely to develop more aggressive subtypes of breast cancer and have lower survival rates for some subtypes that have a relatively good prognosis in older women.

While the reasons for the age-dependent outcome differences are not well understood, one hypothesis is that survival differences result from biological differences in the tumors diagnosed in younger versus older women. The goal of our BroadIgnite project is to characterize the tumor cells and germline cells—the cells that transfer genetic material from one generation to another—from an initial group of eight young patients with metastatic breast cancer in order to better understand the biological mechanisms for these age disparities.

The Approach

With BroadIgnite funding, we’re pursuing this work through an initiative called the Metastatic Breast Cancer (MBC) Project (mbcproject.org), a direct-to-patient platform developed at the Broad to identify and study metastatic breast cancer patients from around the world.

We selected eight young metastatic breast cancer patients under age 40 and performed germline whole-exome sequencing, tumor whole-exome sequencing, and tumor RNA sequencing to gain insight into the mechanisms that may be responsible for the striking differences among older breast cancer patients and young patients.

The Results

Nearly 3,400 patients have registered since the program's launch in October 2015. Our team has successfully sequenced 67 patient samples, including six of the patients under age 40. Our preliminary data helped us secure a $375,000 grant from a major breast cancer foundation. That grant will allow us to sequence an additional 40 young women with metastatic breast cancer, bringing us closer to our ultimate goal of sequencing more than 100 young women for this study.