Women’s Health and Breast Cancer

Biography

Biography: Linda A. deGraffenried

Abstract

Multiple studies have demonstrated that obesity is associated with a worse outcome for most breast cancer subtypes and that obese breast cancer patients do not respond as well as normal weight patients to hormone therapy as well as chemotherapy. While a number of reasons have been proposed to explain this link, including diagnosis bias and complications caused by co-morbidities such as Type II diabetes, recent studies have provided evidence that elevated local cyclooxygenase-2 (COX-2) expression and the resulting increase in prostaglandin E2 (PGE2) production may play an important role. COX-2 upregulation in breast tumors is associated with a poor prognosis, a connection generally attributed to PGE2's direct effects on apoptosis and invasion as well as its stimulation of pre-adipocyte aromatase expression and subsequent estrogen production. Research in this area has provided a strong foundation for the hypothesis that COX-2 signaling is involved in the obesity-breast cancer link. Our recent pre-clinical and clinical data suggest that this inflammation-related signaling modulates several pathways critical to cancer progression in the obese breast cancer patient – but importantly – suppression of this signaling through fairly non-toxic approaches may provide significant clinical benefit and improve response to standard therapies – which will be critical as obesity reaches epidemic levels world-wide