The FDA Office of Women’s Health (OWH) awards research grants for 1-2 year studies to support FDA regulatory decision-making and advance the science of women’s health. OWH has funded research projects that address health issues affecting women across their lifespan. This page highlights OWH-funded research related to cardiovascular disease.
Verification of Novel Predictive Biomarkers of Doxorubicin-induced Cardiotoxicity in Breast Cancer Patients - Li-Rong Yu, PhD/NCTR
Chemotherapy is a major treatment option for cancer patients and anthracyclines (e.g., doxorubicin (DOX)) are commonly used for treating a wide range of cancers. However, they can cause life-threatening heart damage (cardiotoxicity) for some patients. Currently, non-invasive medical imaging tests are the most practical cardiotoxicity monitoring tools; nonetheless they are not sensitive enough for early detection of heart damage. In a preliminary analysis of blood samples from 70 female breast cancer patients taken before and after the first and second cycles of DOX treatments, we identified potential novel blood protein and metabolite biomarkers for predicting heart injury resulted from the treatment. The goal of this study is to verify the predictive performance of these biomarkers in a separate group of 120 new patients. Ultimately, these predictive biomarkers may provide an earlier and better individualized risk assessment in female breast cancer patients of chemotherapy-induced cardiotoxicity, thus providing opportunities for prevention or therapeutic intervention of cardiac injury.
These novel biomarkers could enable personalized female breast cancer therapy tailored toward maximal efficacy and minimal cardiotoxicity and have a potential to assess the safety of promising new therapies.
Effect of Sex Differences on the Drug Absorption, Biological Responses and Adverse Events Elicited by Paclitaxel Containing Medical Devices - Vaishnavi Chandrasekar, PhD/CDRH
According to the American Heart Association, cardiovascular disease is the leading cause of death among women in the United States, accounting for approximately 1 in every 3 female deaths. Peripheral arterial disease (PAD) is associated with reduced blood flow to the extremities due to the buildup of atherosclerotic plaque in the femoropopliteal artery. Recent studies report a high prevalence of PAD in women, particularly at the extremes of ages (>80 years and <40 years). Paclitaxel coated stents and balloons are used to treat PAD. Notably, recent reports of a link between these treatments with increased 2 to 5-year patient mortality rates prompted FDA to urge caution in using these devices. Unfortunately, mechanistic insights are currently lacking, and causes of death have not been determined. The goals of this project are (1) to characterize differences in the uptake, distribution, and accumulation of paclitaxel within atherosclerotic tissues between men and women due to sex-based differences in the plaque composition; and (2) reveal clues about why accumulation and release of paclitaxel from atherosclerotic tissues may increase mortality rates. Different paclitaxel levels in plaques of men and women can potentially affect its ability to inhibit restenosis. Additionally, reservoirs of paclitaxel gathering in the vessel tissue can lead to its slow release in the circulation and accumulation in tissues of downstream organs. We hypothesize that accumulation of paclitaxel in downstream tissues causes a loss of microvasculature in the organs over time contributing to the reported mortality rates in patients receiving paclitaxel-coated stents/balloons. Potential sex-based differences revealed from the proposed studies will be complemented by statistical evaluation of clinical data and adverse event reports to determine clinical significance of our observations. Outcomes from this research will enable FDA to make informed decisions regarding current and potential future use of paclitaxel.