Inmunologically active proteins on a T-cell: T-cell receptor, CD-4, CD-28, PD-1 and CTLA-4 and a calcium channel
Immunologically active proteins on a T-cell. TCR (blue), CD-4 (light blue), CD-28 (dark blue), PD-1 (magenta), CTLA-4 (violet), Ca-channel (dark violet). The T-cell receptor, CD-4 and CD-28 activate T-cells, while PD-1 and CTLA-4 inhibit the activation of T-cells. [selvanegra/GEtty Images]

New immunotherapy treatments offer promise for an aggressive and difficult-to-treat form of breast cancer called triple negative breast cancer, but not all people have equal access to the treatments. Triple negative breast cancer makes up roughly 15% of all breast cancer in the general population, but in African American women that number can be as high as 40-50%. Despite shouldering a much larger burden of disease, African Americans remain severely underrepresented in clinical trials, in some cases comprising only four percent of the cohort population. 

But now, researchers at the Yale Cancer Center have taken a first step in correcting this. In research published on July 29 in the journal Clinical Cancer Research, a large immunotherapy trial looking at efficacy of durvalumab concurrent with neoadjuvant chemotherapy for stage I-III triple negative breast cancer re-opened enrollment to African American women. They extended the trial enrollment so that the patient cohort was representative of the population. The study, which ended up accruing enough patients for African Americans to make 31% of the cohort, found that  there was no difference in the three-year overall survival rate or event-free survival rate by race.

“By excluding a population from studies, we don’t really learn about the efficacy and the toxicity of a particular drug in that group.” said Lajos Pusztai, professor of medicine at Yale School of Medicine and senior author of the study. “By employing a very simple set of administrative measures we made the clinical trial representative of the population,” he said.

Triple negative breast cancer is a very aggressive form of breast cancer that is more likely to spread and recur. The cancer lacks hormone receptors that respond well to targeted treatments, which has traditionally left patients with limited treatment options. Typically, patients had to rely on chemotherapy alone and survival rates hover around 70 percent. But, new immunotherapies have changed the outlook for patients with this devastating type of breast cancer. 

In a previously published clinical trial, Pusztai and his team showed that durvalumab, a checkpoint inhibitor drug, used  in combination with chemotherapy prior to surgery benefited patients with non-metastatic triple-negative breast cancer. Other trials have shown similar results as well. The KEYNOTE-522 trial, for example, which evaluated the immunotherapy drug pembrolizumab plus chemotherapy, boosted the 3-year event-free survival rate to 84.5% compared to 76.8% with chemotherapy alone. 

But, Pusztai’s initial trial did not enroll patients that reflected the racial and ethcni makeup of the surrounding neighborhood in New Haven, Connecticut nor the population that has the greatest burden of disease. To better understand how this treatment benefits African Americans, Pusztai and colleagues created an extension cohort to enroll more patients. They enrolled an additional 67 patients, 21 of whom identified as Black (31 percent of the total cohort). 

The researchers found that there were no statistically significant differences between African American and non-African American patients in s pathologic complete response rates, which were 43 versus 48 percent respectively. In addition there were no significant differences between the rates of metastatic recurrence, which were 14 percent in African American and 17 percent in non-African American patients. 

Pusztai said he was not surprised by the results. “I think when people get the same treatment the same way, their outcomes are very similar.” He believes that marginalization of groups, rather than biology, is to blame for the disparities in this type of cancer. He hopes that in the future, clinical trials will mandate the accrual of patients that are representative of the population. Not only will this ensure treatments are effective across different racial and ethnic groups, but also improve equity and access to better cancer drugs. 

“All groups deserve an opportunity to receive tomorrow’s therapies today,” he said.

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