Analysis of treatment response among more than 100,000 people underscores need for personalized treatments

  • Preoperative chemosensitivity appears key to outcomes
  • Treatment-resistant disease most common in people with aggressive subtypes
  • Researchers look to potential of immune checkpoint inhibitors

BUFFALO, N.Y. — Black patients with early-stage breast cancer who have residual disease after neoadjuvant chemotherapy were more likely to die from the disease than white patients in the same cohort, reports a multidisciplinary team of researchers from Roswell Park Comprehensive Cancer Center. Their findings, newly published in JAMA Network Open, highlight the importance of developing personalized treatment options for people of African descent who develop breast cancer.

Neoadjuvant chemotherapy (NACT) is given to try to shrink the tumor prior to surgery. The Roswell Park study shows that preoperative chemosensitivity — the tumor’s vulnerability to therapy — varies among people of different races and ethnicities. It is usually categorized as very sensitive, sensitive, or refractory — unresponsive to treatment.
The investigators discovered that Black or African American patients were more likely than patients of other races and ethnicities to have disease that was refractory to NACT, especially if they had aggressive cancer subtypes, such as HER2-positive and triple-negative breast cancer (TNBC). Black women are three times more likely than white women to develop TNBC.

Under the direction of Shipra Gandhi, MD, Assistant Professor of Oncology in the Department of Medicine, the Roswell Park team used data collected by the National Cancer Database (NCDB) between 2010 and 2018 for 103,605 patients who were treated with NACT for early-stage breast cancer. Among those patients, 43.2% had disease that was refractory to treatment, while 34.4% were sensitive to treatment and 22.4% were very sensitive.

“Our analysis shows that Black breast cancer patients with sensitive and refractory preoperative chemosensitivity after neoadjuvant chemotherapy had the most unfavorable clinical outcomes compared to all other groups,” says the study’s first author, Arya Mariam Roy, MBBS, a Roswell Park Hematology/Oncology Fellow, Class of 2024. “This was especially true for Black breast cancer patients who still had evidence of cancer following initial treatment.”

Asian and Hispanic patients in those groups had better survival in comparison to white patients, the authors report.

“Standard cancer treatments do not work equally well in people of all races. Our findings underscore the importance of determining predictive biomarkers for more breast cancer subtypes, expanding availability of biomarker-driven therapy for all breast cancer patients, and identifying alternative treatment strategies that may help more Black patients to achieve pathological complete response following cancer treatment,” adds Dr. Roy.

Outcomes varied according to breast cancer subtypes. Compared with other races and ethnicities, Black patients with TNBC had more refractory disease (38% vs. 30%-35%). Among patients with hormone-receptor-positive, ERBB2-negative breast cancer (formerly called HER2-negative), overall, patients had more refractory disease regardless of race or ethnicity (54%). Among patients of all races and ethnicities who had ERBB2-positive disease, Black patients had a lower percentage of very sensitive disease (32% vs. 37%-40%).

Regardless of disease subtype, among patients with refractory or sensitive disease, Black patients had a higher mortality rate than patients of other races and ethnicities. They also had significantly lower three- and five-year overall survival rates whether their disease was refractory, sensitive or very sensitive.

Could immune checkpoint inhibitors (ICIs), a type of immunotherapy, offer African American patients a superior alternative to NACT? Research currently underway at Roswell Park is exploring the potential of ICIs and how patients of different races respond to them. The work is supported by three National Cancer Institute (NCI) grants totaling $13.5 million that were awarded recently to Song Yao, MD, PhD, Vice Chair and Professor of Oncology in the Department of Cancer Prevention and Control, and Christine Ambrosone, PhD, Senior Vice President for Population Sciences and Chair of the Department of Cancer Prevention and Control at Roswell Park.

“Because immune checkpoint inhibitors are the backbone of the neoadjuvant treatment regimen in triple-negative breast cancer,” notes Dr. Gandhi, “we will be following the work of our colleagues with great interest, to see whether they determine that patients of African heritage tend to benefit more from these groundbreaking immunotherapies