Working Paper Article Version 1 This version is not peer-reviewed

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

Version 1 : Received: 29 May 2021 / Approved: 31 May 2021 / Online: 31 May 2021 (12:27:49 CEST)

A peer-reviewed article of this Preprint also exists.

Schmidt, M.; Edlund, K.; Hengstler, J.G.; Heimes, A.-S.; Almstedt, K.; Lebrecht, A.; Krajnak, S.; Battista, M.J.; Brenner, W.; Hasenburg, A.; Rahnenführer, J.; Gehrmann, M.; Kellokumpu-Lehtinen, P.-L.; Wirtz, R.M.; Joensuu, H. Prognostic Impact of Immunoglobulin Kappa C (IGKC) in Early Breast Cancer. Cancers 2021, 13, 3626. Schmidt, M.; Edlund, K.; Hengstler, J.G.; Heimes, A.-S.; Almstedt, K.; Lebrecht, A.; Krajnak, S.; Battista, M.J.; Brenner, W.; Hasenburg, A.; Rahnenführer, J.; Gehrmann, M.; Kellokumpu-Lehtinen, P.-L.; Wirtz, R.M.; Joensuu, H. Prognostic Impact of Immunoglobulin Kappa C (IGKC) in Early Breast Cancer. Cancers 2021, 13, 3626.

Journal reference: Cancers 2021, 13, 3626
DOI: 10.3390/cancers13143626

Abstract

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 1,010 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 including also 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 (Pinteraction = 0.855 and 0.684, respectively). These results show that humoral immunity beneficially influences the DDFS of patients with early TNBC.

Keywords

triple-negative breast cancer; prognosis; immune system; immunoglobulin kappa C

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