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An electrochemical immunosensor was fabricated to identify CA15-3, a biomarker for breast cancer (BC). A composite sensor substrate made of "zeolitic imidazolate framework-8" (ZIF-8) and "reduced graphene oxide" (rGO) was chosen and its conductivity was further improved by the addition of chitosan (CS)-doped gold nanoparticles (AuNPs). The CS@AuNPs are able to conjugate with antibodies via the strong Au-S interaction, which offers multiple active sites for antibody immobilization and enhances the sensor performance. This immunosensor is capable of ultrasensitive detection of CA15-3 by specific antigen-antibody -interactions. In healthy people, normal serum CA15-3 is up to 25 U/mL. Under optimized experimental conditions, the alteration in the signal intensity measured by the sensor was related to the CA15-3 activity. The quantitative relationship was linear over 0.001-400 U/mL with a limit of detection (LOD) of 0.0031 U/mL at a "signal-to-noise ratio" (S/N) of 3 and a "correlation coefficient" (r²) of 0.9983. The developed immunosensor showed great accuracy, stability, and selectivity, and was able to detect CA15-3 in human serum samples. These results validate its potential as a reliable analytical platform for BC diagnosis and early clinical screening.