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Abstract
Benign breast disorders are a significant cause of morbidity and are common among adolescents and the community at large. Macromastia and gynecomastia represent two of these disorders. The broad goal of this study is to use surgically resected adolescent breast tissue to determine the local role of hormones (principally estrogens, androgens, and leptin) and the PI3K/AKT pathway in the pathophysiology of macromastia and gynecomastia. The pathophysiology of tissue overgrowth in macromastia and gynecomastia remains largely unknown. Most cases are idiopathic, and affected patients routinely have normal levels of circulating reproductive hormones. It has been hypothesized that idiopathic macromastia/gynecomastia is a consequence of enhanced end-organ sensitivity to normal levels of gonadal hormones, particularly estrogen. Elevated local estrogen production due to excess aromatization is another proposed mechanism. Our group will test the proliferative and aromatizing influence of estradiol, testosterone, and leptin on cells isolated from adolescent breast tissue. We will acquire surgically resected adolescent breast tissue (overgrowth and control tissue), and use fluorescence-activated cell sorting to isolate luminal epithelial, myoepithelial, and adipocyte cell populations. Western blot and qPCR will confirm and quantify the presence of estrogen, androgen, and leptin receptors. We will perform proliferation assays on the isolated cells, both at baseline and with separate exposure to estradiol, testosterone, and leptin. Finally, we will test the influence of leptin on cellular aromatization. We will compare assay results both within and between cell populations. The PI3K/AKT pathway plays a critical regulatory role in cellular growth, proliferation, and apoptosis. PTEN is an essential negative regulator of this pathway. PTEN deletions/mutations cause breast tissue overgrowth in mice and have been identified in human breast cancer. Somatic gain-of-function PIK3CA mutations are also of interest in this pathway. PIK3CA mutations are common in breast cancer, and recently our group detected PIK3CA mutations in macromastia and gynecomastia tissue. We plan to use immunohistochemistry, western blot, and qPCR to measure PIK3CA, PTEN, and AKT expression in our samples, and compare results between macromastia/gynecomastia and control tissue. Digital droplet PCR and molecular inversion probe sequencing will be employed to identify PIK3CA mutations.

Biography
Dr. Brian Labow is a pediatric plastic and reconstructive surgeon in the Department of Plastic and Oral Surgery at Boston Children’s Hospital. His primary professional activities include clinical practice, translational investigation, and resident education. An overarching theme that links Dr. Labow’s clinical and research activities is the treatment of benign adolescent breast disorders. He founded the Adolescent Breast Center at Boston Children’s Hospital, a service that integrates and coordinates care across multiple disciplines including plastic surgery, adolescent medicine, endocrinology and general surgery. The Center’s registry, of roughly 1300 patients followed longitudinally, provides invaluable information in assessing clinical outcomes and establishing new treatment guidelines. We are now striving to better understand long term surgical outcomes in this population.