Grant: Collaborative Health Research Projects (NSERC partnered)

"Hormonal factors are critical in determining a woman's risk of developing breast cancer. This is true both for women in the general population and for women with an inherited BRCA1 or BRCA2 mutation. Much of the evidence for hormonal breast carcinogenesis comes from clinical and epidemiologic studies of circulating estrogen and other hormones; however, it is believed that local breast tissue levels of hormones are much more relevant than blood levels. Traditionally, scientists and clinicians have not been able to measure breast tissue levels with accuracy because of inadequate technology and access to samples. This problem could be solved if an assay were developed to reliably measure representative hormone levels in a very small amount of breast tissue obtained through a needle biopsy. Surgical removal of the ovaries (i.e., oophorectomy) among women with a BRCA1 or BRCA2 mutation is associated with significant reductions in breast and ovarian cancer risks. We have recently shown that the reduction in risk associated with surgical menopause is much stronger than that associated with natural menopause. This suggests that the postmenopausal ovary is producing hormones that contribute to the risk of breast cancer. Studies directly quantifying levels of androgens, estrogens and aromatase activity in the both the pre- and postmenopausal breast tissue will help elucidate a role of endogenous hormones. We will evaluate a new technology that uses a miniaturized, integrated method for hormone analysis that relies on digital microfluidics and only requires one-microliter in a group of high-risk women by quantifying breast hormone levels before and after oophorectomy. We can then measure the impact of oophorectomy on the tissue levels of these hormones. We propose to develop the technology for this series of experiments. We will collect blood and breast tissue samples using fine-needle microaspiration, a relatively non-invasive "