Isabelle Bedrosian, MD

2012-2013 BCRF Project:
ASCO Conquer Cancer Foundation 2011 Advanced Research Award

Accrual to this clinical trial by Dr. Bedrosian to study whether DNA damage in normal breast tissue can identify women at risk of breast cancer continues steadily. Through the Army of Women organization, Dr. Bedrosian's team has now identified 284 cases of the 330 needed for the study. All these women had a benign breast biopsy prior to developing breast cancer, and the research team is coordinating retrieval of these benign biopsy tissue samples from sites across the country. To date, they have obtained 54 samples representing tissue from 31 women. They are in the process of collecting biopsy samples and questionnaires regarding breast cancer risk factors from these women for the biomarker analyses.

In addition, building on their observation that high levels of DNA damage lead to cell death rather than transformation to cancer, Dr. Bedrosian and her colleagues have started to examine additional conditions that may be of relevance in allowing damaged cells to advance to cancer. Using laboratory models, the investigators have identified one breast cancer relevant growth pathway that appears to be suppressed in normal breast cells exposed to cancer causing genes. They also have preliminary data that suggests that the addition of IGF-1 to the growth conditions of these cells overcomes the suppression this pathway. Blood levels of IGF-1 have long been associated with increased breast cancer risk. Their data suggest one means by which IGF-1 may promote breast cancer is to reverse the suppression of growth pathways normally seen when healthy, non-cancerous cells are exposed to DNA damage. Dr. Bedrosian will continue to validate this laboratory-based observation in patient tissue samples.

Mid-year Progress: In the last six months, Dr. Bedrosian's team has made much progress. They have collected tissue samples and questionnaires from 77 women in the control arm. Given the slow rate of tissue retrieval from institutions around the country, the researchers have modified their approach for analysis of the data from the cancer and cancer free controls in order to complete the study in the next six months. This approach, although less robust than initially designed, should provide the investigators with some preliminary observations about the role of DNA damage as a biomarker of breast cancer risk.

Secondly, building on their observation that high levels of DNA damage lead to cell death rather than transformation to cancer, Dr. Bedrosian's team is continuing to examine additional conditions that may be of relevance in allowing damaged cells to move forward towards cancer. Specifically, they have been investigating the role of one specific breast cancer relevant growth pathway and how it may be responsible for how cells fare under conditions of DNA damage. In the last six months, the investigators have moved this work from laboratory models to patient samples. Initial analyses from the patient samples show the same trends as Dr. Bedrosian's team saw in the lab, namely that this growth pathway appears to be suppressed in normal breast cells and activated with increasing risk of invasive breast cancer.