Tumor-Infiltrating Lymphocytes: A Predictive and Prognostic Biomarker in Neoadjuvant-Treated HER2-Positive Breast Cancer

Heppner BI, Untch M, Denkert C, Pfitzner BM, Lederer B, Schmitt W, Eidtmann H, Fasching P, Tesch H, Solbach C, Rezai M, Zahm DM, Holms F, Glados M, Krabisch P, Heck E, Ober A, Lorenz P, Diebold K, Habeck JO, Loib S (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Clinical Cancer Research American Association for Cancer Research

Book Volume: 22

Pages Range: 5747-5754

Journal Issue: 23

DOI: 10.1158/1078-0432.CCR-15-2338

Abstract

PURPOSE: We elucidated the value of tumor-infiltrating lymphocytes (TIL) as an independent predictor for pathologic complete response (pCR) rate and as a prognostic marker for disease-free survival (DFS) in patients with HER2-positive breast cancer in the neoadjuvant setting. EXPERIMENTAL DESIGN: We evaluated stromal TILs in 498 HER2-positive breast cancer samples of the neoadjuvant GeparQuattro (G4) and GeparQuinto (G5) trials. Levels of TILs were determined as a continuous parameter per 10% increase and as lymphocyte-predominant breast cancer (LPBC; ≥ 60% TILs), and correlated with pCR rate and DFS. RESULTS: In the complete cohort, HER2-positive LPBC cases had a significantly increased pCR rates compared with non-LPBC types. They were significant predictors for pCR in univariate (10% TILs: OR 1.12, P = 0.002; LPBC: OR 2.02, P = 0.002) and multivariate analyses (10% TILs: OR 1.1, P = 0.014; LPBC: OR 1.87, P = 0.009). This effect was also detectable in the trastuzumab-treated (10% TILs: OR 1.12, P = 0.018; LPBC: OR 2.08, P = 0.013) but not in the lapatinib-treated subgroup. We identified a low-risk (pCR/LPBC) and a high-risk group (no pCR/no LPBC) regarding DFS. In triple-positive breast cancer, TILs are of more prognostic relevance than pCR. CONCLUSIONS: We could demonstrate the predictive and prognostic impact of TILs in HER2-positive breast cancer in the neoadjuvant setting. In combination with pCR rate, TILs may help to stratify prognostic subgroups, thereby guiding future therapy decisions. Clin Cancer Res; 22(23); 5747-54. ©2016 AACR.

Authors with CRIS profile

Peter Fasching Professur für Translationale Frauenheilkunde und Geburtshilfe

Involved external institutions

Universitätsklinikum Schleswig-Holstein (UKSH) DE Germany (DE) SRH Wald-Klinikum Gera DE Germany (DE) Johanna-Etienne-Krankenhaus DE Germany (DE) Charité - Universitätsmedizin Berlin DE Germany (DE) GBG Forschungs GmbH (German Breast Group) DE Germany (DE) HELIOS Kliniken DE Germany (DE) St. Vincenz Krankenhaus Limburg DE Germany (DE) St. Barbara-Klinik Hamm DE Germany (DE) Luisenkrankenhaus Düsseldorf DE Germany (DE) Centrum für Hämatologie und Onkologie Bethanien DE Germany (DE) Universitätsklinikum Frankfurt am Main (KGU) DE Germany (DE) Klinikum Chemnitz DE Germany (DE)

How to cite

APA:

Heppner, B.I., Untch, M., Denkert, C., Pfitzner, B.M., Lederer, B., Schmitt, W.,... Loib, S. (2016). Tumor-Infiltrating Lymphocytes: A Predictive and Prognostic Biomarker in Neoadjuvant-Treated HER2-Positive Breast Cancer. Clinical Cancer Research, 22(23), 5747-5754. https://doi.org/10.1158/1078-0432.CCR-15-2338

MLA:

Heppner, Barbara Ingold, et al. "Tumor-Infiltrating Lymphocytes: A Predictive and Prognostic Biomarker in Neoadjuvant-Treated HER2-Positive Breast Cancer." Clinical Cancer Research 22.23 (2016): 5747-5754.

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