TY - JOUR
T1 - Prognostic impact of immunoglobulin kappa c (Igkc) in early breast cancer
AU - Schmidt, Marcus
AU - Edlund, Karolina
AU - Hengstler, Jan G.
AU - Heimes, Anne Sophie
AU - Almstedt, Katrin
AU - Lebrecht, Antje
AU - Krajnak, Slavomir
AU - Battista, Marco J.
AU - Brenner, Walburgis
AU - Hasenburg, Annette
AU - Rahnenführer, Jörg
AU - Gehrmann, Mathias
AU - Kellokumpu-Lehtinen, Pirkko-Liisa
AU - Wirtz, Ralph M.
AU - Joensuu, Heikki
N1 - Funding Information:
Funding: This work was supported by the Federal Ministry of Education and Research (BMBF, NGFN project Oncoprofile, number 01GR0816). The funder had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
Funding Information:
Conflicts of Interest: M.S. reports personal fees from AstraZeneca, Eisai, Lilly, MSD, Novartis, Pantarhei Bioscience, Pfizer, Roche, and SeaGen outside the submitted work. Institutional research funding from AstraZeneca, BioNTech, Eisai, Genentech, German Breast Group, Novartis, Palleos, Pantarhei Bioscience, Pierre-Fabre, and Roche. Travel reimbursement from Pfizer and Roche. In addition, M.S. is named inventor on patent EP 2390370 B1 and patent EP 2951317 B1 issued. K.A. reports personal fees from AstraZeneca, Pfizer, Roche. M.J.B. received honorarium and travelling expenses from Roche Pharma AG, Tesaro Bio GmbH, Glaxo Smith Kline, Clovis Oncology, Astra Zeneca, Pharma Mar GmbH, Celgene, Pierre Fabre Pharma GmbH. S.K. received speaker honoraria from Roche Pharma AG. He received research funding from Novartis and travel reimbursement from PharmaMar. A.H. reports personal fees from AstraZeneca, Celgen, GSK, LEO Pharma, MedConcept GmbH, Med update GmbH, Medicultus, PharmaMar, Pfizer, Promedicis GmbH, Softconsult, Roche Pharma AG, Streamedup! GmbH, Tesaro Bio Germany GmbH. M.G. is named inventor on patents for breast cancer prognosis and prediction (EP1954830 B1, EP2066805 B1, EP2390370 B1, EP2553119 B1, EP2737081 B1, EP2845911 B1 and EP 2951317 B1. P.-L.K.-L. received honorarium and travelling expenses from BMS and Sanofi. R.M.W. is founder & employee of STRATIFYR Molecular Pathology. H.J. is the Chair of the Scientific Advisory Board at Orion Pharma and at Neutron Therapeutics Ltd. and owns stock of Orion Pharma and Sartar Therapeutics. The other authors declare no conflict of interest.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - Immune system
KW - Immunoglobulin kappa C
KW - Prognosis
KW - Triple-negative breast cancer
U2 - 10.3390/cancers13143626
DO - 10.3390/cancers13143626
M3 - Article
AN - SCOPUS:85110429850
SN - 2072-6694
VL - 13
JO - Cancers
JF - Cancers
IS - 14
M1 - 3626
ER -
