Weight is a critical factor contributing to an increase in the incidence of breast cancer (BC) and reduced survival outcomes for women after menopause. More than 50% of all women and 70% of post-menopausal women newly diagnosed with BC are overweight, putting them at increased risk for larger and more aggressive tumors containing markers of high proliferation, more recurrence-prone hormone receptor positive tumors, and a death rate nearly two times higher than women with BC who are at a healthy weight. Nearly 90% of women with BC will gain weight during or following chemotherapy treatment, with those already overweight likely to add the most new weight into survivorship. Treatment associated weight gain is correlated with poorer treatment outcomes, BC recurrence, and reduced survival odds; risks exacerbated in women following menopause where weight gain as well as deposition and redistribution of adipose around waist and hips is linked to reduced levels of ovarian produced estrogen. Clinical studies have been unable to correlate diet or exercise patterns with chemotherapy associated weight gain or to demonstrate diet and exercise interventions reliably lead to weight loss in this population. Adipose is recognized as metabolically active tissue producing cytokines and hormones that work together with skeletal muscle to regulate intake behaviors, satiety, glucose uptake, fat metabolism, and energy expenditure. However, adiposity associated low level chronic inflammation, dysfunctional glucose homeostasis, and increased insulin resistance remain underexplored factors contributing to treatment associated weight gain. The purpose of this study is to explore treatment associated weight and metabolic profiles using a clinically relevant chemotherapy triplet across two well explicated mouse models of reproductive senescence. The findings of this study will be used to generate testable hypotheses to explore mechanisms underlying this weight gain and to support intervention studies to complement ongoing human symptom science studies. Further, this project is designed to broadly expose studies to symptom science research as well as create compensated opportunities for student engagement in specific research endeavors related to this project. The School of Nursing at the University of Maryland, Baltimore has a diverse student body, graduating more than 600 entry into practice students each year as well as more than 100 advanced practice nurses educated at the doctoral level. In addition, we maintain a full enrollment of research focused doctoral students, graduating on average 12 per year. Strategies outlined in this proposal are designed to build on existing infrastructure as well as talents and skills of faculty to enrich the research environment here at UMB.
Weight is a critical factor in the incidence of breast cancer in women after menopause. In addition, nearly 90% of post-menopausal women with breast cancer will gain new weight during and after chemotherapy, resulting in poorer treatment outcomes, increased risk for breast cancer recurrence, and reduced survival odds. Animal models proposed in this study will aid in understanding mechanisms underlying this poorly understood weight gain with great potential to design interventions to moderate this increasingly significant clinical problem in cancer care.
