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Article

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

1
Department of Obstetrics and Gynecology, University Medical Center Mainz, 55131 Mainz, Germany
2
Leibniz Research Centre for Working Environment and Human Factors (IfADo) at Dortmund TU, 44139 Dortmund, Germany
3
Department of Statistics, TU Dortmund University, 44221 Dortmund, Germany
4
Bayer AG, 42113 Wuppertal, Germany
5
Cancer Centre, Tampere University Hospital and University of Tampere, 33520 Tampere, Finland
6
STRATIFYER, 50935 Köln, Germany
7
Department of Oncology, Helsinki University Hospital and University of Helsinki, 00290 Helsinki, Finland
*
Author to whom correspondence should be addressed.
Both authors contributed equally.
Academic Editor: Peter Kern
Cancers 2021, 13(14), 3626; https://doi.org/10.3390/cancers13143626
Received: 29 May 2021 / Revised: 9 July 2021 / Accepted: 16 July 2021 / Published: 20 July 2021
(This article belongs to the Special Issue Breakthroughs in Cancer-Related Immunotherapy)
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 (Pinteraction = 0.855 and 0.684, respectively). These results show that humoral immunity beneficially influences the DDFS of patients with early TNBC. View Full-Text
Keywords: triple-negative breast cancer; prognosis; immune system; immunoglobulin kappa C triple-negative breast cancer; prognosis; immune system; immunoglobulin kappa C
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MDPI and ACS Style

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. https://doi.org/10.3390/cancers13143626

AMA Style

Schmidt M, Edlund K, Hengstler JG, Heimes A-S, Almstedt K, Lebrecht A, Krajnak S, Battista MJ, Brenner W, Hasenburg A, Rahnenführer J, Gehrmann M, Kellokumpu-Lehtinen P-L, Wirtz RM, Joensuu H. Prognostic Impact of Immunoglobulin Kappa C (IGKC) in Early Breast Cancer. Cancers. 2021; 13(14):3626. https://doi.org/10.3390/cancers13143626

Chicago/Turabian Style

Schmidt, Marcus, Karolina Edlund, Jan G. Hengstler, Anne-Sophie Heimes, Katrin Almstedt, Antje Lebrecht, Slavomir Krajnak, Marco J. Battista, Walburgis Brenner, Annette Hasenburg, Jörg Rahnenführer, Mathias Gehrmann, Pirkko-Liisa Kellokumpu-Lehtinen, Ralph M. Wirtz, and Heikki Joensuu. 2021. "Prognostic Impact of Immunoglobulin Kappa C (IGKC) in Early Breast Cancer" Cancers 13, no. 14: 3626. https://doi.org/10.3390/cancers13143626

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