NCI GRANT WILL HELP RESEARCHERS LEARN HOW BREASTFEEDING PROTECTS AGAINST TRIPLE-NEGATIVE BREAST CANCER

The National Cancer Institute has awarded a $2.2 million, five-year grant to help OSUCCC – James researchers led by principal investigator Bhuvaneswari Ramaswamy, MD, address cancer disparity by defining the molecular link between breastfeeding and triple-negative breast cancer (TNBC). 

Ramaswamy, associate professor in the Division of Medical Oncology at Ohio State and member of the Translational Therapeutics Program at the OSUCCC – James, and her colleagues state in their project abstract that African-American women with breast cancer face higher mortality rates due to a greater incidence of aggressive TNBC. The scientists note that population studies have linked reduced rates of breastfeeding among black women to this higher TNBC, but the mechanism for this circumstance is unknown.

With this grant, Ramaswamy’s team—which includes co-investigators Ramesh Ganju, PhD, Sarmila Majumder, PhD, and Gina Sizemore, PhD, all of Ohio State’s cancer program—proposes to define molecular changes that occur in the breasts after pregnancy, determine how a lack of breastfeeding leads to increased risk of TNBC and provide a treatment option for mothers who cannot breastfeed.

Their long-term objective is “to reduce the risk of developing aggressive TNBC, especially for African-American women, by discovering how prolonged breastfeeding protects the breast from this risk” and thereby to address the disparity of breast cancer outcomes among these patients.

The researchers state that they have developed mouse models for studying gradually involuting (GI-prolonged breastfeeding) vs. abruptly involuting (AI-short breastfeeding) mammary glands.

“We have shown dramatic shifts in cellular composition of the mammary epithelial cell compartment and global changes in inflammatory markers and, importantly, we have observed precancerous hyperplastic lesions within 120 days postpartum in the AI glands,” they write, adding that these precancerous glands highly express the transcription factor Elf5, a key gene expressed by luminal progenitor cells—the cell-of-origin for TNBC.

“Based on these studies, we hypothesize that lack of breastfeeding not only alters the cellular composition and increases inflammation, but also leads to a higher risk of developing TNBC through Elf5-mediated aberrant differentiation,” they write. “In this proposal, we will use innovative approaches, including novel mouse models and patient samples, to delineate the link between breastfeeding and TNBC.”

They believe their work will help reduce disparity in breast cancer-related mortality among African-American women by identifying preventive strategies for TNBC, and that it could also lead to a discovery of agents that could help women who are unable to breastfeed by reducing their TNBC risk.