Abstract P4-07-17: Association between plasma-based sequential windowed acquisition mass spectrometry (SWATH-MS) and invasive disease free survival (iDFS) in HR+/HER2- early breast cancer in the CANTO cohort

Abstract Background: The definition of breast cancer (BC) prognosis has historically relied on clinico-pathological factors. Novel omics markers including proteomic analyses could improve our understanding of the biological host drivers of breast cancer recurrence and survival. We aimed at identifying patients (pts) at high risk of recurrence based on proteomic markers in plasma.Methods: CANTO is a multicenter, prospective cohort study of stage I-III BCS (NCT01993498). Plasma samples were collected on HR+/HER2- pts at diagnosis (dx) and analyzed by SWATH-MS, implemented by Biognosys AG (Schlieren, Switzerland), resulting in a relative quantification of the abundance of 500 proteins in the plasma. A Cox model was fitted to estimate to associate proteomic and clinical variables with the primary endpoint IDFS Clinical covariates consisted of age, stage and grade. An adaptive Lasso method was used to perform model selection. The discrimination performances of the model were assessed on 100 random train-test partitions of the cohort. Results: There were 457 pts with analyzed plasma samples. The median age at dx was 59.3 years, and the repartition of cancer stage was 52% for stage I, 37% for stage II and 11% for stage III. The mean duration of follow-up was 5.4 years, and 53 (11.5%) IDFS events (non local recurrences, second primary cancers and deaths) were reported. In total, 7 proteins were selected by the adaptive Lasso process; associated with the age, the stage and the grade at dx, 3 proteins were retained as having a significant impact on the IDFS: GTP-binding nuclear protein Ran (RAN), involved in cell division and GTP metabolic process, C4b-binding protein alpha-chain (C4BPA), involved in complement activation, and prothrombin (THRB), involved in acute-phase response and blood activation. Concordance indices were computed on 100 random test subsets of the cohort for the model with clinical variables only (0.67+/- 0.08), for the model with selected protein features only (0.74 +/- 0.07) and for the model with both proteomic and clinical covariates (0.75 +/-0.06). Conclusion: The discrimination performances of the estimated model suggest that proteomics provide relevant markers associated with BC prognosis. Validation on an independent validation set is required. Host related plasma proteins represent an avenue worth exploring to improve our understanding of BC relapse risk Table 1.Estimated hazard ratios of the linear Cox model.FeaturesHR* (95% CI)p-valuesRAN (for 1 SD increase)0.66 (0.51-0.85)<0.005THRB (for 1 SD increase)1.43 (0.99-2.06)0.05C4BPA (for 1 SD increase)1.44 (1.02-2.02)0.04stage--II vs I1.68 (0.82-3.46)0.16III vs I4.29 (1.88-9.75)<0.005HR = hazard ratio CI = confidence interval * adjusted by age and grade Citation Format: Antonin Della Noce, Stergios Christodoulidis, Antonio Di Meglio, Julie Havas, Alicia Tran-Dien, Fabrice André, Ines Vaz-Luis, Paul-Henry Cournède, Stefan Michiels. Association between plasma-based sequential windowed acquisition mass spectrometry (SWATH-MS) and invasive disease free survival (iDFS) in HR+/HER2- early breast cancer in the CANTO cohort [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-07-17.