Metastatic Triple-Negative Breast Cancer: The Urgent Need for Research

The racial disparities in metastatic triple-negative breast cancer are sobering. Research shows Black women have nearly three times the risk of getting it. They’re also 28% more likely to die from the disease. 

“There’s an urgent need for clinical research surrounding racial disparities and metastatic disease,” says Ricki Fairley, CEO and co-founder of TOUCH, The Black Breast Cancer Alliance. Fairley is also a survivor of metastatic triple-negative breast cancer. “We know Black women are more likely to develop this form of breast cancer, but we don’t know why. When they do develop the disease, there are very few treatments available for them.” 

Most often, treatment is usually chemotherapy or immunotherapy. Doctors will use several systemic treatments until the disease gets worse or there is an unacceptable toxicity that puts the person’s overall health at risk. 

 Additionally, triple-negative breast cancer itself makes up only about 10% to 15% of all breast cancers. 

“It’s such a small number that drug companies aren’t focused on that audience when they can develop drugs for the other 90% of breast cancer patients.” 

In addition, Black metastatic breast cancer patients only represent about 3% of people in clinical trials. 

“As a result, we don’t know or even have a good sense of how well these drugs work in Black women,” says Marya Shegog, PhD, health equity and diversity director for the Lazarex Cancer Foundation in Danville, CA. “But that information is crucial if we are going to make a dent in these racial disparities.”

What Might Be Some Reasons Black Women Are More at Risk?

“Anecdotally, we do know they do tend to be diagnosed with the condition later,” says Fairley. She recalls one 38-year-old Black women who went to her doctor with a breast lump. Her doctor dismissed her concerns for 2 years, until her first mammogram at age 40 revealed stage III triple-negative metastatic breast cancer. “She ended up dying, and if her cancer had been caught 2 years earlier, that might not have happened,” says Fairley.

But more research needs to be done into the genetic reasons why Black women are at higher risk for triple-negative breast cancer, says Fairley. The International Center for the Study of Breast Cancer Subtypes (ICSBCS) at New York-Presbyterian/Weill Cornell Medical Center in New York City is currently conducting a study. That research has shown that triple-negative breast cancer is associated with African ancestry, particularly Western Sub-Saharan African ancestry. 

One theory is that this is due to a mutation in ACKR1. About 70% of Americans with West African ancestry carry a mutation in the ACKR1 gene, which protects them against malaria. But it also may make Black women with this ancestry more likely to have cellular changes that can cause aggressive triple-negative breast cancer, says Fairley. 

A 2022 study took triple-negative breast cancer cells from Black and white women, then grew them in a laboratory setting. They found that the cells from Black women grew more quickly, and when they were placed into mice, they grew into new tumors faster and spread more quickly. 

“When we analyzed these cells, we found that two genes, GLI1 and Notch1, were more active in cells that came from African American women,” says study author Dipali Sharma, PhD, a professor of oncology at the Johns Hopkins University School of Medicine in Baltimore. 

She’s currently studying using several experimental inhibitors for each of these two genes with various chemotherapies. 

“Eventually, hopefully we’ll be able to find one that works well, and test it in patients,” she says. “Our hope is that this research can lead the way to close the survival gap between Black and white women with triple-negative breast cancer, particularly metastatic triple-negative breast cancer.”

Clinical Trials for Metastatic Triple-Negative Breast Cancer

There is also some promising research on treatments for metastatic triple-negative breast cancer. They include:

Sacituzumab govitecan-hziy (Trodelvy) + pembrolizumab (Keytruda). Sacituzumab govitecan-hziy is approved as a second-line treatment for women with metastatic triple-negative breast cancer. Researchers are studying whether it can be used along with pembrolizumab as a first-line treatment for women with locally advanced or metastatic triple-negative breast cancer. Sacituzumab govitecan-hziy targets cancer-expressing cells, while pembrolizumab stimulates the immune system. The thought is that people given this combination will have a better response, says Oluchi Oke, MD, an assistant professor in the Department of Breast Medical Oncology at the University of Texas MD Anderson Cancer Center.

Enhertu. This drug is being studied for HER2-low breast cancer. Recent research has found that it cuts the risk of disease progression or death by 50%, and the risk of death by 36%, compared with chemotherapy. The hope is that it will soon be studied – and have similar effects – in those with triple-negative breast cancer, says Dorraya El-Ashry, PhD, chief scientific officer of the Breast Cancer Research Foundation. 

ARTEMIS. This is a novel clinical trial at MD Anderson Cancer Center that develops personalized therapies for women with triple-negative breast cancer. “We know that half of triple-negative breast cancer patients go into remission with standard chemotherapies,” says Oke. “But about half don’t, and they may go on to develop metastatic breast cancer. So we are using different immunotherapies and targeted therapies on them, to see if any help.”

Barriers to Clinical Trials

Unfortunately, while these trials are all promising, there are many barriers, says Oke. 

“In general, we’ve seen a decrease in enrollment in clinical trials among African American patients across the board,” she says. But there are a few barriers for clinical trials on metastatic triple-negative breast cancer in particular:

Implicit bias. “Doctors do not invite black women into trials. They assume that since a woman is a single mom, she won’t comply or drop off, or she won’t have transportation to get there,” says Fairley. A survey by the Metastatic Breast Cancer Alliance, for example, found that while 80% of Black patients with metastatic breast cancer said they would consider joining a clinical trial, only 40% were offered the chance. 

Medical mistrust. “Every day, I speak to Black women with metastatic breast cancer who have a fear of the unknown, and that includes clinical trials,” says Fairley. “They don’t trust doctors, or researchers, or scientists. But once I explain to them what a clinical trial is, and how there are standards of care and no one gets a sugar pill and dies, they are much more willing to sign up.”

Poor marketing. “Medical researchers still don’t recruit in minority or poorer communities,” says Fairley. “Drug companies themselves also don’t know how to reach out to them. If you look at commercials for some of the breast cancer drugs, for example, there are images of beautiful white women sailing on boats or playing golf. That is not the life of a Black woman. They need to see women who look like them getting a certain drug.”

“I tell every Black woman with metastatic triple-negative breast cancer that her best option is to get involved in a clinical trial,” says Fairley. 

But it can be daunting to look for one on your own. One of the best ways to find one is to reach out to TOUCH, which has a wide array of resources for Black breast cancer patients. They also have a clinical trial locator at Search Clinical Trials | When We Trial. Other resources include:

BreastCancerTrials.org 

Triple Negative Breast Cancer Foundation

Metastatic Breast Cancer Alliance

Photo Credit: KTSDesign / SCIENCEPHOTOLIBRARY / Getty Images

SOURCES:

Ricki Fairley, CEO and co-founder of TOUCH, The Black Breast Cancer Alliance.

Dipali Sharma, PhD, professor of oncology, Johns Hopkins University School of Medicine, Baltimore.

Oluchi Oke, MD, assistant professor, Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston.

Dorraya El-Ashry, PhD, chief scientific officer, Breast Cancer Research Foundation.

Marya Shegog, PhD, health equity and diversity director, Lazarex Cancer Foundation, Danville, CA.

Cancer Medicine: “Relationship of Established Risk Factors with Breast Cancer Subtypes.” 

JAMA Oncology: “Evaluation of Racial/Ethnic Differences in Treatment and Mortality Among Women with Triple-Negative Breast Cancer.” 

American Cancer Society: “Triple Negative Breast Cancer.” 

Breast Cancer Research Foundation: “ASCO 2022 Metastatic Breast Cancer Research Update.” 

University of Illinois Cancer Center: “Is an Anti-Malaria Gene Tied to Triple-Negative Breast Cancer?” 

eLife: “Concomitant Activation of GLI1 and Notch1 Contributes to Racial Disparity of Human Triple Negative Breast Cancer Progression.” 

Gilead Pharmaceuticals: “Gilead Announces Clinical Trial Collaboration with Merck to Evaluate Trodelvy in Combination with KEYTRUDA.” 

Metastatic Breast Cancer Alliance: “BECOME: Black Experience of Clinical Trials and Opportunities for Meaningful Engagement.”

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