Prognostic Impact of Immunoglobulin Kappa C (IGKC) in Early Breast Cancer

Abstract

Simple Summary We examined the relevance of immunoglobulin kappa C (IGKC), an important part of the humoral immune system, in early breast cancer. To our knowledge, our results confirm for the first time previous retrospective findings of a cancer recurrence protective role of IGKC in a large cohort of early breast cancer patients who were treated in the prospective, randomized FinHer clinical trial. We show that an increased amount of IGKC in the tumor is linked to longer distant metastasis-free survival, especially in patients whose breast cancer does not express hormone receptors or human epidermal growth factor receptor-2. This type of breast cancer often has poor prognosis. Since an improved outcome is associated with the presence of tumor-infiltrating IGKC expressing immune cells, this may be a further argument for the use of immunotherapies in these patients. We studied the prognostic impact of tumor immunoglobulin kappa C (IGKC) mRNA expression as a marker of the humoral immune system in the FinHer trial patient population, where 1010 patients with early breast cancer were randomly allocated to either docetaxel-containing or vinorelbine-containing adjuvant chemotherapy. HER2-positive patients were additionally allocated to either trastuzumab or no trastuzumab. Hormone receptor-positive patients received tamoxifen. IGKC was evaluated in 909 tumors using quantitative real-time polymerase chain reaction, and the influence on distant disease-free survival (DDFS) was examined using univariable and multivariable Cox regression and Kaplan-Meier estimates. Interactions were analyzed using Cox regression. IGKC expression, included as continuous variable, was independently associated with DDFS in a multivariable analysis also including age, molecular subtype, grade, and pT and pN stage (HR 0.930, 95% CI 0.870-0.995, p = 0.034). An independent association with DDFS was also found in a subset analysis of triple-negative breast cancers (TNBC) (HR 0.843, 95% CI 0.724-0.983, p = 0.029), but not in luminal (HR 0.957, 95% CI 0.867-1.056, p = 0.383) or HER2-positive (HR 0.933, 95% CI 0.826-1.055, p = 0.271) cancers. No significant interaction between IGKC and chemotherapy or trastuzumab administration was detected (P-interaction = 0.855 and 0.684, respectively). These results show that humoral immunity beneficially influences the DDFS of patients with early TNBC.