The laboratory of Thea Tlsty, Ph.D., professor at the University of California, San Francisco, studies the regulation of cancer initiation in human tissues. At the conference, she will be discussing the use of biomarkers to evaluate the risk of future breast tumor formation in women diagnosed with ductal carcinoma in situ (DCIS).
Fifteen to thirty percent of women with DCIS go on to develop tumors within ten years after a lumpectomy. Unfortunately, many patients end up being treated too aggressively (needless mastectomies) or not aggressively enough.
Nuclear grade, surgical margins, and tumor size are all measured in the clinic, but none have been found to have strong enough predictive value to affect therapeutic decisions.
Interestingly, Dr. Tlsty found that cells expressing high levels of p16 and/or COX-2, when coupled with proliferation, go on to become basal-like invasive tumors. These particular biomarkers indicate an abrogated response to cellular stress; cells overexpressing them that continue to proliferate have bypassed pRb-mediated signals to senesce.
In contrast, cells with high p16 and/or COX-2, but low proliferation, have an intact Rb checkpoint and senescent program and do not go on to become tumorigenic. These biomarkers can be measured years before tumors actually arise, and thus can be used clinically to help dictate individualized treatment options.
Richard Bender, M.D., the chief medical director of Agendia, will be talking about the company’s development of genomic biomarkers for prognosis and prediction in early-stage breast cancer. Agendia is marketing MammaPrint, which measures the expression profiles of 70 different genes in early-stage breast cancers.
MammaPrint was designed to specifically predict which 30% of patients are at a high risk of recurrence, which it does remarkably well, according to Dr. Bender; it has a hazard ratio of 10, whereas most prognostics hover around 3–4. As a side benefit, these are the same 30% that are sensitive to chemotherapy. Dr. Bender notes that this type of gene-expression profiling is a “way of personalizing treatment for patients.”
Agendia also has TargetPrint, which quantitates ER, PR, and HER2 expression in breast cancer. In contrast to MammaPrint, this test was designed to determine which drugs should be given to which patients.