Background: For African American (AA) women in the US, breast cancer (BC) is the leading cancer diagnosis and the second leading cause of cancer death. The rising prevalence of obesity and related comorbidities are important contributors to widening racial disparities in BC outcomes. 82% of AA women are obese or overweight, compared to 64% of Non-Hispanic White (NHW) women. BC mortality rates are 40% higher in AA women, and incidence rates surpassed NHW women in 2013. Obesity is linked to poorer BC outcomes through upregulation of leptin, cytokines, and hormone expression. Conversely, weight loss and/or increased physical activity decrease inflammation and estrogen expression, decrease cellular growth factor signaling and angiogenesis, increase antitumor immunity, and reduce overall BC risk. Methods: Between 2011 and 2014, 246 AA breast cancer survivors were recruited and randomized to either the Moving Forward interventionist-guided or self-guided weight loss program. Results showed significant weight loss, improved diet, increased physical activity, and increased social support. In addition to collecting anthropometric and behavioral data, the study team banked serum samples for the majority of participants at baseline, six months (post-intervention) and twelve months (follow-up). For all samples, weight loss outcomes were recorded, and potential biomarkers were explored between groups. Results: Interventionist-guided study participants exhibited greater improvements than self-guided control participants for weight loss (-3.49kgs vs -1.27kgs, p = <0.0001) and % weight loss (3.6% vs 1.4%, p = 0.001). Among all participants, those losing >5% of their body weight showed significant improvements in leptin (65.6 ± 28.3 vs. 45.0 ± 23.3 at baseline and 6 months, respectively, p = <0.0001) and c-peptide (805.3 ± 470.6 vs. 632.3 ± 453.4 at baseline and 6 months, respectively, p = 0.0001). Planned studies will utilize RNA sequencing approaches to fully elucidate the role of non-coding RNAs in lifestyle intervention outcomes. Conclusions: Early changes in triglycerides, leptin, and HbA1c are detectable in participant serum samples and are likely linked to alterations in body composition, inflammatory cytokines and mitochondrial bioenergetics. Our future directions for this study are completely novel in their use of next generation sequencing to examine noncoding RNA-mediated mechanisms of reduced breast cancer risk, and the first to focus specifically on outcomes of lifestyle intervention in AA women.

Citation Format: Jessica Olson, Patricia Sheehan, Giamila Fantuzzi, Lisa Sharp, Melinda Stolley. Mechanistic pathways and novel prognostic indicators of lifestyle intervention outcomes for African American breast cancer survivors [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr A076.