Schreier S.Budchart P.Borwornpinyo S.Arpornwirat W.Lertsithichai P.Chirappapha P.Triampo W.Mahidol University2023-06-182023-06-182022-01-01Journal of Cancer Research and Clinical Oncology (2022)01715216https://repository.li.mahidol.ac.th/handle/20.500.14594/83884Background: Breast cancer residual disease assessment in early-stage patients has been challenging and lacks routine identification of adjuvant therapy benefit and objective measure of therapy success. Liquid biopsy assays targeting tumor-derived entities are investigated for minimal residual disease detection, yet perform low in clinical sensitivity. We propose the detection of CD44−related systemic inflammation for the assessment of residual cancer. Methods: Circulating CD44+/CD45− rare cells from healthy, noncancer- and cancer-afflicted donors were enriched by CD45 depletion and analyzed by immuno-fluorescence microscopy. CD44+ rare cell subtyping was based on cytological feature analysis and referred to as morphological index. AUC analysis was employed for identification of the most cancer-specific CD44+ subtype. Results: The EpCam−/CD44+/CD24−/CD71−/CD45−/DNA+ phenotype alludes to a distinct cell type and was found frequently at concentrations below 5 cells per 5 mL in healthy donors. Marker elevation by at least 5 × on average was observed in all afflicted cohorts. The positive predicted value for the prediction of malignancy-associated systemic inflammation of a CD44+ rare cell subtype with a higher morphological index was 87%. An outlook for the frequency of sustained inflammation in residual cancer may be given to measure 78%. Conclusion: The CD44+ rare cell and subtype denotes improvement in detection of residual cancer disease and may provide an objective and alternative measure of disease burden in early-stage breast cancer.Biochemistry, Genetics and Molecular BiologyArticleSCOPUS10.1007/s00432-022-04330-52-s2.0-851380591621432133536100762