Carol J. Fabian, MD

To develop strategies to prevent breast cancer in moderate- to high-risk women that also improve their overall health and quality of life.

Impact

Breast cancer prevention drugs such as tamoxifen or aromatase inhibitors dramatically reduce the risk of developing breast cancer, but many women will discontinue their use due to side effects that can initiate or worsen menopausal symptoms. Dr. Fabian is focusing on finding prevention strategies that women are more likely to adopt, ones that not only lower breast cancer risk but also help with common health issues like menopause symptoms, weight management, or cholesterol. By combining cancer prevention with improvements in quality of life, Dr. Fabian may be able to expand options for women at higher risk and reduce barriers to prevention.

Progress Thus Far

Dr. Fabian and her team completed an initial pilot study testing bazedoxifene and conjugated estrogens (BZA/CE, Duavee®) preventative agents. Initial tests suggest this drug combination improves cholesterol and insulin sensitivity. They are also testing the diabetes drug tirzepatide (Mounjaro®/Zepbound®) in a trial of high-risk women with obesity. The study has enrolled quickly and has already shown that the target receptor of one of tirzeptide’s actions is present in breast tissue. This suggests tirzepatide may act directly on breast cells, offering a possible explanation for how it could reduce cancer risk beyond its benefits for weight and metabolism. They also launched two new trials: one comparing acolbifene (an experimental anti-estrogen drug with potentially fewer side effects) to low-dose tamoxifen in younger women, and another testing whether omega-3 fatty acids can boost the effectiveness of low-dose tamoxifen in older women.

What’s next

Over the next year, she and her team will assess changes in mammographic breast density, body composition, and metabolic health across multiple ongoing trials. They plan to expand genetic testing in tissue samples, including markers of estrogen response and resistance, to better understand how these drugs work at the cellular level. In the tirzepatide trial, they are exploring cutting-edge approaches such as spatial transcriptomics and circulating biomarkers, which may provide a non-invasive way to track changes in breast cancer risk. Together, these efforts will allow them to refine biomarkers, compare different prevention strategies, and move closer to offering women safer and more acceptable options for lowering breast cancer risk.