Current Research and Scholarly Interests
Together with collaborators at Stanford and in Vancouver, British Columbia, I have worked to define an immunohistochemical correlate to a gene expression panel originally developed at Stanford, that was applied to a series of approximately 900 breast cancers on a tissue microarray and showed a similar outcome stratification (see Nielsen et al). The combination of gene and protein (immunohistochemical) expression analysis of breast cancer has redefined the clinical understanding of breast cancer biology (including description of the "basal-like" subset of tumors), and will have significant impact on future clinical diagnosis and treatment of this disease.
In addition, ongoing work arising from the initial tissue microarray immunohistochemical studies has identified an interesting expression pattern of the fatty acid synthase protein, raising the possibility that this protein may highlight a reserve cell or stem cell population in the breast. This is especially interesting, as the gene that corresponds to this protein co-clusters with genes that define the "basal-like" subtype of breast cancer, supporting the hypothesis that these particularly aggressive tumors arise from a breast stem cell population.
Ultimately, I hope to improve techniques to amplify tumor cell RNA so that gene expression studies can be performed on fine needle aspiration material. With a limited panel of genes, breast tumors could then be stratified into variious "good-acting" and "bad-acting" subtypes, information which could direct neoadjuvant treatment using a relatively non-invasive and rapid procedure (fine needle aspiration biopsy). As therapeutic targets are discovered with refined gene analysis and subsequent drug development, neoadjuvant therapy will likely play a larger role in breast cancer treatment, and diagnosis and risk stratification using material obtained from fine needle aspiration would be ideal in this setting.
While adjunct research tools are exciting and interesting, the role of traditional cytomorphologic diagnosis and correlation with imaging features cannot be underestimated, as these two tools along with clinical examination, are the mainstay of early detection and diagnosis programs. I am currently completing a project correlating radiologic features to cytologic impression and histologic diagnosis to show the overall accuracy and efficacy of ultrasound-guided fine needle aspiration biopsy with immediate cytologic adequacy assessment.