Researchers at the Indiana University Melvin and Bren Simon Comprehensive Cancer Center are spearheading a pioneering study to unravel the biological underpinnings of aggressive breast cancers in Black women. Led by Dr. Harikrishna Nakshatri, a breast cancer researcher at the IU School of Medicine and a key researcher at the Vera Bradley Foundation Center for Breast Cancer Research at the IU Simon Comprehensive Cancer Center, the investigation holds promise for targeted treatments that could significantly reduce disparities in breast cancer outcomes among Black women.
While breast cancer incidence is now considered lower among Black women, they face significantly poorer outcomes, often developing more aggressive triple-negative breast cancers at a younger age. “Even after you correct for socioeconomic and healthcare access factors, African ancestry is still associated with the worst outcomes,” Nakshatri emphasized. Nakshatri’s lab has been dedicated to uncovering the influence of genetic ancestry on the biology of normal breast tissue and its implications for developing aggressive breast cancers.
Women of African descent had more PZP cells in their normal breast tissue than women of Caucasian descent, according to a previous study under Nakshatri’s direction. Notably, PZP cell numbers increase when Caucasian women develop breast cancer, while they are naturally more abundant in Black women.
Adding to this, Nakshatri and his team showed that PZP cells have a significant effect on how cancer cells behave and grow, especially when they interact with epithelial cells, which is where breast cancer usually starts. Researchers have also found that PZP cells are one of the sources of metaplastic breast cancers (MBC), which are rare and aggressive and make up less than 1% of all breast cancers. The team drew upon tissue samples from the Susan G. Komen Tissue Bank at the IU Simon Comprehensive Cancer Center, the world’s sole repository of healthy breast tissue, to conduct this research.
“When these PZP cells interact with epithelial cells, they trigger the production of a crucial protein called interleukin-6. This prompts distinct behavior in the epithelial cells and activates a signaling pathway known as STAT3,” Nakshatri explained. “This is what makes tumors originating from the epithelial cells more aggressive.”
The findings have laid the foundation for an upcoming clinical trial led by Kathy Miller, MD, a prominent figure in oncology at IU School of Medicine. Miller also serves as the Ballvé Lantero professor of oncology and holds the position of associate director of clinical research at the cancer center, in addition to her role as a researcher at the Vera Bradley Foundation Center.
“This study could help us determine if physicians need to consider the genetic ancestry of the person when deciding on possible treatments for breast cancer,” Nakshatri stated. Based on the biology of normal breast tissue, he said the study represents a significant departure from conventional treatment approaches, offering new hope for more effective, targeted treatments in the fight against breast cancer.
