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Investigating the Biology of Black Women’s Metastatic Breast Cancer: A Q&A with Dr. Nikhil Wagle

By BCRF | July 2, 2021

The BCRF researcher talks about his current BCRF-supported project dedicated to researching metastatic breast cancer in Black women

There’s no single silver bullet to eliminate the devastating disparities Black women face in breast cancer care and outcomes. But we do know that Black women have long been underrepresented in breast cancer trials and that decades of research have suggested biology may play a role in how the disease affects them.

BCRF investigator Dr. Nikhil Wagle’s new research project, supported by The Estée Lauder Companies, Inc., aims to attack disparities from both of these key angles. He and his team will actively recruit and enroll 1,000 Black women living with metastatic breast cancer and then perform genomic sequencing on 250 of their tumors to identify molecular features that could inform further research and potential targeted therapies.

BCRF spoke with Dr. Wagle about breast cancer disparities, unanswered questions in metastatic disease research, and more.

Your work is focused on breast cancer genomics and understanding the biology of metastatic disease. How did you get interested in these areas?

My work is an intersection of a bunch of different experiences that largely came out of my training as an oncologist. One of the first things that was really striking to me at the time was that patients with advanced breast cancer, across all tumor types, eventually develop resistance to treatments. Then we don’t have good therapeutic options for them. And so very quickly I decided I wanted to focus my attention on finding better therapies and ways to overcome resistance for patients with metastatic breast cancer. Secondly, while I was training, there were also increasing opportunities for precision medicine, where we could molecularly profile a tumor to identify vulnerabilities, and then in some cases, that would lead us to use a therapy. We sometimes saw dramatic responses, even if they were short-lived. This highlighted the opportunities of genomic profiling and precision medicine. These areas really stuck out to me as places that urgently needed research. I ultimately started my own lab focused on cancer genomics (looking at the underlying DNA, RNA, proteins, and more within a tumor cell), precision medicine, and therapeutic resistance across a variety of cancers before honing in on my initial clinical interest in metastatic breast cancer.

Several large studies have looked at the genomic landscape of breast cancer. Why is further research still needed?

We have really important genomic and molecular studies in breast cancer—with the Cancer Genome Atlas funded by the US government being one of the largest and most important. But there were a bunch of gaps in the data that need to be filled in. Some of those gaps are because of what was profiled and who was enrolled. Most earlier studies didn’t focus on metastatic disease, didn’t have any information about treatments, often didn’t collect multiple samples over time to look at tumor evolution and resistance, and didn’t have the opportunity to collect parallel types of information from patients. There was definitely an opportunity for more studies focusing exclusively on metastatic breast cancer, which, for example, is the motivation for BCRF’s Founder’s Fund and the AURORA US and EU studies.

Overlaid on all this is the question of representation. I would say that in the cancer genomics field, in general, there’s been a dearth of inclusion and equal representation. Black and brown patients and other underrepresented minorities have not been included in studies to a degree that would make them truly representative. And that’s not to say that studies don’t exist. The Cancer Genome Atlas did have representation. Other studies have tried to remedy this, but we definitely need more. This project funded by BCRF gives us the opportunity to study metastatic breast cancer with accompanying information—like clinical data, patient-reported data, and serial samples—and ask questions on metastatic breast cancer in Black or African American patients that haven’t been well-answered.

Why is it important that breast cancer research include more Black women? Why have these patients been so understudied?

One is because of the disparities that exist in breast cancer. Black women die at younger ages and get more aggressive or widespread disease. We don’t fully understand the reasons for those disparities, so more research is needed. Research needs to represent people, so that advances are meaningful to all. The fact that Black women have been underrepresented in breast cancer research and clinical trials means that we don’t necessarily know whether conclusions drawn from those studies are applicable to them. We actually know that in some cases they’re not. A lack of knowledge coupled with disparities makes this an urgent issue.

What is the Metastatic Breast Cancer Project for those who are unfamiliar, and what role is it playing in your BCRF-supported project?

The Metastatic Breast Cancer Project (MBCproject) is a patient-partnered research project we’ve been running for about five-and-a-half years. We ask patients with metastatic breast cancer across the United States and Canada to partner with us and share their medical information, their biospecimens (including saliva, blood, and tumors), and their voices and experiences. The goal is to let everyone with metastatic breast cancer be counted. BCRF has supported the MBCproject now for many years. I’m really grateful. BCRF saw this was an opportunity to include people who have not traditionally been included in this type of research.

Patients just go to our website and register. We ask them to send a consent form that gives us permission to obtain and analyze their tumor specimens and medical records, which our team handles so patients don’t have to. We mail patients a saliva kit and a form to take to their next blood draw. They just need to drop those in the mail back to us. Then we do comprehensive genomic and molecular analyses, and we link all that information with the data we get from patients’ medical records and surveys. After we strip out all personal identifiers, we put this information in a publicly available database multiple times a year. Traditionally, researchers keep all data to themselves until they write a paper and then maybe they share data. Our data is shared first so research happens simultaneously.

Tell us about the goals of your current BCRF project.

This project builds on the framework of the MBCproject and allows us to focus in on patients who are Black or African American and who have metastatic breast cancer. There are two components.

The first is a real focus on outreach and enrollment. This is not the scientific part of the project, but I would say it’s equally important. It’s about building trust in the community and figuring out the right ways to engage and enroll patients in this project. We’re doing this through a variety of mechanisms, including forming relationships with African American communities, involving patient advocates, and developing social media campaigns, videos, and communications.

Then the second part of the project, after we collect these specimens, involves performing our analyses. We’re asking: What molecular and genomic features can we identify in Black patients with metastatic breast cancer? We’ll then share that data to create a resource that will help further our understanding of metastatic disease resistance and potential initial targets for treatment.

BCRF has clearly been committed to this important area of research, and I really appreciate the support for this project.