Abstract P6-05-26: BORIS: A potential novel breast cancer biomarker

Abstract

Abstract Background: Breast cancer is the most common cancer in the UK excluding non-melanoma skin cancers. Worldwide 1.38 million women were diagnosed with breast cancer and caused 458,503 deaths (13.7% of cancer deaths in women) in 2008. Presently there are no early predictors for detection of breast cancer. There is a pressing need to identify “biomarkers” that complement or replace the currently available diagnostic tools. BORIS (Brother of the Regulator of Imprinted Sites) is a protein belonging to the cancer testis antigen gene family. It is present in early spermatocytes and is absent in women. It is aberrantly expressed in various malignancies. Our discovery of the appearance of BORIS in leukocytes and in cancer tissue of breast cancer patients offers a promise. As the patients who received neoadjuvant chemotherapy showed lower BORIS expression, BORIS may be an indicator of patient's response to treatment. We reasoned that the appearance of BORIS in the “high risk” women may predict the presence of the condition and hence BORIS may be considered as a potential early breast cancer biomarker. We also assessed the potential of BORIS as a marker of treatment monitoring in metastatic breast cancer (MBC). Methods: 1) Familial breast cancer study The aim is to recruit 300 women between 40 and 50 years of age who have high familial risk of breast cancer. Blood samples (10 ml) are collected from each participant every year for 5 consecutive years at the time of their annual mammogram. BORIS levels in leukocytes were assessed by Immunocytochemistry (measured as immunoreactivity score (IRS)) and Western Blot Analysis and were correlated with their respective annual mammograms. If a woman shows an increase in BORIS level and her corresponding mammogram is negative, she is offered MRI scan to confirm the presence or absence of the disease. 2) MBC study We recruited 64 patients who are either on chemotherapy or endocrine therapy. BORIS expression in the leukocytes of MBC patients was assessed in pre- and post- treatment samples by Immunocytochemistry and Western Blot Analysis. Results: 1) In the first year, 129 women have been recruited. Protein and RNA samples were obtained from the blood leukocytes and BORIS expression assessed by different methods. The BORIS expression measured as immunoreactivity score (IRS) was found to be higher in the family history group (IRS 0.36 ± 0.004) than in healthy donors (IRS 0.17±0.068). Positive BORIS expression was observed in 8% of participants on Western blot analysis. In one participant, BORIS was detected in leukocytes by both methods. This woman had a positive mammogram and had been histologically diagnosed of Invasive Ductal Carcinoma of breast. Clinically, mammograms of all other participants were negative. 2) BORIS was not found in the leukocytes of patients with advanced breast cancer. Conclusions: Presence of BORIS expression in the leukocytes of one woman correlated with the mammographic and histological evidence of breast cancer. Likewise, the absence of BORIS in remaining participants correlated with the negative results of their mammograms. These findings support the hypothesis that BORIS may be an early biomarker of breast cancer. Its absence in MBC patients rules out its use as biomarker for treatment monitoring. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-05-26.