Influence of oncogenic protein sequestration by platelets on early and stage-specific breast cancer detection.

e12601 Background: Mammography remains the standard modality for breast cancer (BC) screening but has several limitations. There is a critical need for minimally invasive markers that can aid in distinguishing benign, non-invasive lesions from those likely to progress to invasive BC. Platelets are nature’s transport mechanism for delivery of growth factors and inhibitors. Assaying the platelet proteome, Hessian Labs developed HeLP (Hessian Labs Personalized) test designed to identify early malignancy, as well as its grade, and invasiveness. The test is based on a discovery that platelets sequester oncogenic regulators against a concentration gradient in plasma early in tumor development. Hence, it has the potential to differentiate benign from invasive BC at various stages, stratifying the need for intervention. Methods: Platelet samples from 120 women with BC were analyzed using a discovery data-independent acquisition mass spectrometry (DIA-MS). The identified differentially expressed platelet-associated proteins, were prioritized using ClariaIQ , a proprietary computational platform that ranks proteins based on their relevance to stage-specific oncogenic pathways and established Cancer Hallmarks, to identify stage- and grade-associated proteomic signatures and create the HeLP panel. Results: DIA-MS identified multiple platelet sequestered proteins that were differentially expressed between indolent disease and invasive BC. ClariaIQ prioritization resulted in the selection of 13 proteins for inclusion in the HeLP breast cancer assay. We present two examples: SAA1 and SERPIN proteins demonstrated differential expression between healthy, benign breast lesions and malignant invasive disease (Table 1). SAA1 peaks in early BC and SERPIN in advanced stages. With SAA1, in HER negative BC the levels rise to an average of 285,000 RE units when compared to HER2 positive BC. Conclusions: Platelet sequestered protein signatures provide clinically relevant information regarding breast cancer status, grade, and invasiveness. The findings support the robustness of the signal, and a more patient-specific signature than traditional plasma or serum biomarkers. It suggests a role for HeLP as a minimally invasive adjunct to mammography to improve diagnostic stratification and therapeutic decision-making. Disease Group SAA1 Mean (RE) SAA1 SD (RE) SERPIN A3 Mean (RE) SERPIN A3 SD (RE) Healthy Controls 119,592 206,349 490,231 279,017 Benign Breast Lesions 622,187 50,855 341,102 153,144 Stage I Breast Cancer 1,223,865 1,878,654 742,409 466,468 Stage II Breast Cancer 663,369 1,970,265 922,381 844,512 Stage III Breast Cancer 437,853 662,211 705,994 597,399 Stage IV Breast Cancer 225,265 384,826 1,068,874 1,415,934 RE=Relative Expression units. N=20 subjects included in each group.