Model building and quantitative analysis of a tandem immuno-capturing assay as a screening tool for breast cancer.

ABSTRACT

The onset of breast cancer appears to occur, on average, a decade earlier in Mexican women in comparison to American or European women. Early detection and prevention of breast cancer are of crucial importance to increase survival and improve quality of life. Based on the molecular elucidation of critical events leading to breast carcinogenesis, a tandem immuno-capturing blood test was developed as a quantitative population screening assay in view of providing a cost-effective and non-invasive alternative to population screening. Clinical analysis of 63 Mexican women within an age group of 35-70, revealed that Interstron activity increases from 800+/-65 IUJPA (Interstron Units) in the asymptomatic normal women to 994+/-100 IUJPA in the symptomatic/benign group, reaching 1289+/-81 IUJPA in the cancerous group. Accordingly, activity thresholds were established at 800 and 1200 IUJPA respectively, encompassing three risk groups (i) Healthy Otherwise Normal (<800 IUJPA); (ii) Grey Risk Area (>800 and <1200 IUJPA), and (iii) At Risk group (>1200 IUJPA). Taking into account both baseline and clinical case reports, the Healthy Otherwise Normal group and the At Risk group were mostly homogeneous in nature, comprising a population of normal and cancer patients respectively. The Grey Risk group is heterogeneous, likely reflecting a transitional nature towards a potential early stage of breast disease development. Based on these results, a screening algorithm was developed as the underlining principle for population surveillance encompassing over 30,000 Mexican women. The current screening results have enabled us to objectively prioritize medical attention to approximately 1 in 8 women out of the general population mapped within the At Risk group. Overall, our findings suggest that monitoring Interstron activity units provides a valuable quantitative screening analysis as to selectively streamline the population of women in need of early medical counseling and/or mammography, thereby enhancing both the quality and cost-effectiveness of preventative population surveillance programs targeting breast cancer.