Association of cancer antigen 15-3 with distant recurrence in immunohistochemically defined breast cancer subtypes in Canadian Cancer Trials Group MA.32

Abstract Background Circulating levels of Cancer Antigen (CA) 15-3 have been associated with distant breast cancer (bc) recurrence; data on bc subtypes is sparse. We examined associations of CA 15-3 with outcomes across immunohistochemically defined bc subtypes in MA.32. Methods 3649 participants with T1-3, N0-1, M0 bc were randomized; 2740 (75.1%) provided blood at entry (mean 278 days post diagnosis) and 6 months later. Prognostic associations of baseline and 6-month change in CA 15-3 with distant recurrence free survival (DRFS) were examined in luminal (ER/PgR positive, HER2 negative), triple negative (ER, PgR, HER2 negative) and HER2 positive (any ER/PgR) bc using Cox proportional hazards models. Results Mean age was 52 years. bc was luminal in 1589 (58.7%), triple negative in 655 (24.2%) and HER2 positive in 464 (17.1%). Median follow-up was 96 months. CA 15-3 at study entry was not associated with outcome in any subtype. Rising CA 15-3 at 6 months was associated with poor DRFS in luminal and triple negative bc (HR per 25% increase = 1.41, P < 0.0001 and 1.35, P < 0.0001, respectively). New elevations in CA 15-3 at 6 months were adversely associated with DRFS in those with luminal or triple negative bc (HR 4.14, 95% CI 2.69-6.38, P < 0.001 and HR 3.57, 95% CI 1.59-7.99, P = 0.002, respectively). In HER2+ bc, CA15-3 was not associated with DRFS. Conclusion Rising CA 15-3 was associated with reduced DRFS in luminal and triple negative bc but not in HER2 positive bc. Clinical Trial Registration ClinicalTrials.gov NCT01101438