Anatomical Heterogeneity in Longitudinal CA15-3 and CEA Rises Preceding Metastatic Breast Cancer Progression

Cancer antigen 15-3 (CA15-3) and carcinoembryonic antigen (CEA) are used alongside clinical and radiologic assessment in metastatic breast cancer, but progression may occur without a preceding increase in either marker. We examined whether this differed according to newly documented anatomical involvement around radiographic progression. We analyzed 4517 radiographic progression events from 1592 patients in the Memorial Sloan Kettering-Clinical History of Real-World Data (MSK-CHORD) breast cancer cohort. A qualifying marker rise was defined as a ≥25% increase in CA15-3 or CEA from the preceding running nadir, occurring more than 30 days after treatment-line initiation and within 90 days before progression. Anatomical associations were estimated using patient-clustered logistic generalized estimating equations. A total of 1650 events (36.5%) occurred without a preceding qualifying rise. This proportion ranged from 24.8% for newly documented liver involvement to 45.1% for central nervous system involvement. Liver involvement was associated with lower odds of progression without a preceding rise (adjusted OR 0.53, 95% CI 0.40-0.71), whereas central nervous system involvement was associated with higher odds (OR 1.60, 95% CI 1.19-2.14). The associations remained consistent across sensitivity analyses. Thus, among documented radiographic progression events, the frequency of a preceding CA15-3 or CEA rise differed according to newly documented anatomical involvement.