Abstract PS4-02-07: A novel serum protein-based assay for monitoring response to therapy and recurrence of breast cancer

Abstract Background: Breast cancer (BC) is the most frequent cancer in women from western countries. 30% of BC patients are likely to develop recurrence and risk remains indefinitely. Monitoring recurrence and evaluating response to therapy are important aspects of clinical decision making in the treatment of BC. According to clinical guidelines, BC follow-up is based on clinical examination and bilateral mammogram only. Serum tumor markers such as cancer antigen 15-3 (CA15-3) and other imaging techniques are used by many physicians, but without clear recommendations from clinical societies. We used an in-house developed modular proteomic array platform, the Matrix Protein Array to identify a protein biomarker (BF-09 antigen) that was differentially expressed in BC tissues versus normal counterparts, present in early and late stages and measurable in serum. The development of an ELISA assay to establish its diagnostic performance in discriminating BC patients from healthy individuals and benign cases was previously described 1-2. The present study is designed to assess the utility of our assay for monitoring BC recurrence and therapy response. Methods: The concentration of BF-09 antigen was measured by ELISA assay in 379 retrospective serial serum samples from 85 BC patients and changes in biomarker concentration were correlated to change in disease status as determined by standard of care. BC patient samples were obtained from a biobank at the IRCCS San Raffaele Pisana Research Center (Italy). Patients were followed for up to 10 years (median 23.1 months, range 2.9-203 months) and were examined periodically with imaging to document the remission or progression of the disease. 67% of patients were diagnosed with early-stage BC (I-III) while 33% had metastatic breast cancer (stage IV). Treatments received by patients were neoadjuvant therapy (NAT, 16.5%), adjuvant therapy (AT, 18.8%), metastatic breast cancer therapy (MBCT, 35.3%), or multiple therapies (AT± NAT and/or MBCT, 29.4%). A significant increase or decrease in BF-09 concentration was defined as a change equal or superior to 2.5 times the %CV of the assay as compared to a previous point and interpreted as progression or no progression, respectively. Sensitivity (SE), specificity (SP), negative (NPV) and positive predictive values (PPV) as well as overall concordance of the assay with disease status were calculated. Results: Total concordance of BF-09 serum level with disease status was not affected by BC subtypes (luminal A/B, HER2 positive or triple negative) or stage (Chi-square, p≥0.05). Overall performance of the assay in detecting progressive disease was 81.8% sensitivity at 92.6% specificity with 68.7% PPV and 96.2% NPV. The BF-09 assay could identify BC recurrence both in early BC patients following curative surgery/treatment and in metastatic BC patients during therapy follow up, in some cases years before patients started suffering from clinical symptoms. We were also able to show the utility of BF-09 antigen assay in monitoring therapy response in the neoadjuvant setting prior to surgery. Conclusion: Our findings show that the BF-09 biomarker assay quantitatively reflects therapy response both in the (neo)adjuvant therapy and metastatic therapy settings and detects cancer relapses in a timely manner. This appears to be the first time a protein biomarker has shown high accuracy and applicability for these clinical indications and this could offers new opportunities for BC patient management. Further testing is needed to confirm these results in a prospective trial population. 1 Chavany et al. New breast cancer marker BF-09 is overexpressed in tumor extracts and secreted in serum, Biochemistry and Biophysics Reports, Volume 43, 2025,102097. 2 Chavany et.al. A Serum Biomarker for the Early Detection of Breast cancer. Cancer Res (2024) 84 (9_Supplement): PO5-07-08. Citation Format: J. Dea, C. Chavany, R. P. Valle, R. Hernandez-Gonzalez, M. Jendoubi. A novel serum protein-based assay for monitoring response to therapy and recurrence of breast cancer. [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-02-07.