Development of a blood based breast cancer test for Indian population.

Abstract

#5013 Background: The incidence of breast cancer (BC) in India is increasing as the society becomes more westernized. No national screening program exists and there is a high mortality rate which may be linked to the late detection of the disease. Here we report the development of a gene expression based blood test to detect BC. We have previously presented data from European/US cohort with accuracies ranging between 75% - 82% suggesting that test can be developed to early detect breast cancer. We now report the findings from a multi-centre study initiated to test the efficacy of the test for early detection of breast cancer (BC) in an Indian population.
 Methods: A multicentre-study was initiated where blood samples were collected from women recruited in 5 different groups 1) early stage BC, 2) late stage BC, 3) women at high risk - without BC, 4) benign breast lesions, 5) without abnormal mammographic findings. The women recruited in group 3 is a part of ongoing prospective study. Recruitment was balanced between pre- and post-menopausal women among the remaining groups. Samples were collected in PAXgene tubes and shipped to a central laboratory where RNA extraction and quality control. Gene expression analysis was performed using TaqMan® low density arrays (LDA's) containing a BC-specific gene signature in a 96-gene assay format. A total of 442 samples from groups 1, 2, 4 and 5 were used to develop the India model and estimate its prediction efficacy. The 442 samples were divided between a training cohort (N=292) and a test cohort (N=150). Gene expression data of the training cohort were used to develop the breast cancer specific diagnostic model and its performance was determined by predicting the class of the independent test cohort.
 Results: The developed model correctly predicted the class of 110/150 test samples, resulting in an overall accuracy of 73%. Prediction performance was similar for early and late stage cancer and for benign and healthy (no mammographic findings). No significant difference in diagnostic performance was seen between pre- (57/75 correctly predicted) and post-menopausal (53/75 correctly predicted) women indicating the clinical value of our test in younger women.
 Conclusion: The Indian multi-centre study demonstrates the utility of the BC-specific 96 assay signature in detecting BC in an Indian population with similar diagnostic performance seen between women with late stage (stage 2+) and early stage BC. We have previously presented data from European and US cohorts with similar diagnostic performance suggesting the broad applicability of our test. The Breast Cancer test showed the same high level of accuracy in pre-menopausal as in post-menopausal women indicating its clinical applicability in younger women where mammography is of less value due to dense breast tissue. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5013.