Prognostic significance of immunoglobulin kappa C in node-negative breast cancer is both conserved across and independent from molecular subtypes.

Abstract

10616 Background: Immunological defense mechanisms play an important prognostic role in breast cancer. We examined the prognostic impact of immunoglobulin kappa C (IGKC) in 766 node-negative breast cancer patients without adjuvant systemic therapy according to molecular subtypes. Methods: IGKC (probe set ID 211645_x_at) was analysed utilizing microarray based gene-expression data of three independent and previously published cohorts of node-negative breast cancer patients (Mainz, Rotterdam, TRANSBIG). In addition to IGKC, we examined the prognostic impact of age, histological grade, tumor size, estrogen receptor (ER) and HER2. Furthermore, we investigated the prognostic significance of IGKC in luminal (ER+/HER2-), erbB2-like (HER2 +), and basal- like (ER-/HER2-) molecular subtypes, respectively. Metastasis-free survival (MFS) was analyzed with univariate and multivariate Cox regression. Results: Patients with higher expression of IGKC showed better MFS in the whole cohort of patients (HR 0.795, 95% CI 0.711-0.890, p < 0.001). Using multivariate Cox regression, IGKC retained its independent prognostic significance (HR 0.731, 95% CI 0.621-0.861, p < 0.001). Besides IGKC histological grade (HR 2.318, 95% CI 1.522-3.532, p < 0.001), tumor size (HR 1.536, 95% CI 1.131-2.085, p = 0.006), and HER2 (HR 1.829, 95% CI 1.079-3.101, p = 0.025) showed an independent association with MFS. 521 patients (68%) belonged to the luminal subtype, 106 (14%) were erbB2-like, and 139 (18%) basal-like, respectively. Prognostic impact of IGKC was conserved across luminal (HR 0.796, 95% CI 0.688-0.923, p = 0.002), erbB2-like (HR 0.542, 95% CI 0.387-0.757, p < 0.001), and basal-like (HR 0.760, 95% CI 0.600-0.963, p = 0.023) subtypes, respectively. In multivariate analysis IGKC had independent prognostic significance additionally to molecular subtypes (HR 0.746, 95% CI 0.664-0.837, p < 0.001). Conclusions: IGKC has independent prognostic impact in breast cancer. Its prognostic significance is both conserved across and independent from molecular breast cancer subtypes. Incorporating IGKC should lead to a more appropriate assessment of outcome in node-negative breast cancer. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Siemens Healthcare Diagnostics Siemens Healthcare Diagnostics