Breast cancer test may make bad chemotherapy recommendations for Black patients, UIC study shows

While the rest of the world was in the throes of the pandemic, Valletta Howard was wrapping her mind around a breast cancer diagnosis.

After finding a lump in her left breast in April 2021, she confirmed it with a mammogram and ultrasound in May 2021. It was invasive ductal carcinoma, grade 2, she recalled. Two weeks later, Howard underwent outpatient surgery to have it removed. She was optimistic that she wouldn’t have to endure chemotherapy or radiation. But the medical professionals sent the tissue sample out for testing, and chemotherapy and radiation became a reality.

“It was a big shock. I was not ready for that due to the fact in October 2020, my mom was diagnosed with pancreatic cancer. So from October 2020 up until May, when I found out I had breast cancer, I was helping her go through her treatment,” Howard said. “(Initially) she was happy that I didn’t have to go through chemo because she had gone through it herself. Then when I had to start chemo, she started taking care of me. When I found out I had to have chemo, my mom was devastated because she didn’t want me to go through what she had went through.”

The Austin resident endured chemo once a week, every other week, from August through December of 2021, and 30 days of radiation four days a week after that.

On the heels of Howard’s cancer journey, Dr. Kent Hoskins, professor of oncology at University of Illinois Chicago, wants to make sure a test that’s often used to decide whether breast cancer patients should get chemotherapy is as effective for Black women as it is for other populations.

Hoskins, the senior author of a recent study published in the Journal of the National Comprehensive Cancer Network, and other researchers found the oncotype test, which tests tumor tissue for a group of 21 genes, could be problematic. The commonly ordered biomarker test is used to guide doctors’ recommendations for patients with estrogen receptor-positive breast cancer and helps identify which tumors are likely to be most aggressive; that translates to who makes a good candidate for chemotherapy. Hoskins said such a test may be making bad recommendations for some Black women, leading them to forgo chemotherapy when it might have helped.

“We know there is underrepresentation of Black women in trials that were used to develop this test; we know that Black women are more likely to have biologically aggressive tumors and that there are differences in tumor biology,” Hoskins said. “That concerns us that maybe this test is not fully and accurately reflecting prognoses for Black women.”

Researchers conducted analyses on a national database that included test results and death records for more than 70,000 women with early-stage, estrogen receptor-positive tumors. Although more research needs to be done, the exploratory investigation found the test’s cutoff point for recommending chemotherapy for Black women should be lowered.

Researchers and Hoskins suspect the cause of the treatment gap is due to Black women’s tumors being less likely to respond to estrogen-blocking pills than tumors in other women. So chemotherapy would help improve outcomes for Black women more than it would for women who benefit from the pills alone, Hoskins said.

The UIC team is continuing to add to the research. Previous research found that although Black women are more likely than white women to get triple-negative breast cancer, they aren’t more likely to die from it. Yet they are more likely to die from the more common estrogen-receptor-positive form. And while much attention has been paid to the negative outcomes for Black women who have triple-negative breast cancer, that type of cancer makes up only about 20% of breast cancer cases for Black women, Hoskins said.

“Remember that all women are getting endocrine therapy, and some got chemotherapy in addition,” Hoskins said. “What we’re looking at is how much better is the survival rate if you add chemotherapy versus the endocrine therapy alone. The difference was greater in young Black women in particular compared to young white women. Now the question becomes: Is that because the chemotherapy works better, or because the endocrine therapy doesn’t work as well in Black women? Either one of those would give you a bigger difference.

“This needs to be confirmed with additional study, but in our study, the chemotherapy effect appeared the same,” Hoskins said. “What appeared to be different was how well the endocrine therapy worked. It looks like it doesn’t work as well in Black women. Therefore, if you give chemotherapy, you can overcome that, negate that difference.”

Endocrine therapy slows or stops the growth of hormone-sensitive tumors by blocking the body’s ability to produce hormones. Chemotherapy, which is usually given intravenously, uses drugs to destroy cancer cells and prevent tumor growth.

Hoskins said the UIC study shines a light on what happens years later, if inclusion and diversity is not in the mix when data is being collected in clinical trials: The exclusionary deficits snowball. He said everyone needs to work harder to improve inclusion in research, funding and pharmaceutical areas.

“If you have underrepresentation in the original trial, not only can it potentially skew the results of the original trial, but what has happened more and more is people trying to leverage information from one trial for other purposes,” Hoskins said. “You just magnify the problem. Now we have a test that was developed and validated in populations that do not reflect the U.S. population demographically, and in particular, that have underrepresentation of racial and ethnic minority women.

“If there were no differences in anything, then that wouldn’t be a problem,” he said. “But there are differences. We’re assuming that a test developed in one population is going to perform exactly the same in other populations, which maybe that’s true, but good chances are it’s not true.”

A new initiative by the Lynn Sage Breast Cancer Foundation is trying to rectify underrepresentation in cancer clinical trials. The Chicago Breast Cancer Research Consortium is a partnership among University of Chicago Medicine, the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, and RUSH University System for Health. The consortium will allow patients to participate in drug trials previously unavailable to them without leaving their own providers. It will create a network of trial sites that diversifies the patient pool.

The Chicago Department of Public Health commended the consortium for its joint initiative to improve access to clinical trials, particularly for minority populations and those who face barriers to participation.

“This focus reflects CDPH’s own investments in comprehensive breast health programs that, through partners, provide screening mammograms, navigation support and innovative community outreach to Black and Latina women,” said Dr. Olusimbo Ige, commissioner of the Chicago Department of Public Health.

The Lynn Sage Breast Cancer Foundation is giving the initiative $1.8 million in an attempt to remove barriers for those who cannot afford to participate in trials. Part of the donation will be earmarked for expenses like travel and child care to ensure equity among all cancer patients.

“This might be a lifeline and also a ray of hope,” said Laura Sage, co-chair of the Lynn Sage Breast Cancer Foundation. “2024 is about putting the infrastructure in place. We do really want to launch at least one trial in 2024, but the aspiration is to have at least three to five trials by 2026.”

Dr. Rita Nanda, director of breast oncology at UChicago Medicine; Dr. William Gradishar, chief of hematology and oncology at Northwestern Medicine; and Dr. Ruta Rao, oncologist and medical director at RUSH University Cancer Center, are all on board with handling the consortium at their respective institutions.

Nanda said the infrastructure for the network will be housed at the University of Chicago, but all three colleagues will work collaboratively as part of a steering committee to enroll patients in the trials and help implement the research and design.

“Our goal is to focus on those who are underrepresented in clinical trials,” Nanda said. “We have a real opportunity here with the diversity that we’ve got in Chicago to improve on that. We’re starting with the three academic centers in the city that already have the infrastructure to do trials. We’ll start there, and try to build.

“My hope is that we’re going to see some great success in the first couple years,” Nanda said. “And then we can reach out to other organizations in the Chicagoland area, not just in the city, but beyond, wherever patients may want to participate in trials.”

Sage envisions the consortium expanding beyond the three institutions, and perhaps being a model for other areas.

“Breast cancer, like all other cancers, is not just one disease; the more data sampling we can get, the more that we can help patients,” Sage said.

Howard, who will be on medication for six to seven more years to make sure the cancer stays at bay, said she is open to participating in a study.

“I caught it early on,” she said. “I’m an advocate now. When anybody talks about breast cancer, I do put it out there for people, family, friends, everybody: ‘Don’t wait; go immediately.’ A lot of women don’t do it. I was lucky.”