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Clinical Trial
. 2013 Dec 2;8(12):e79775.
doi: 10.1371/journal.pone.0079775. eCollection 2013.

Prospective validation of immunological infiltrate for prediction of response to neoadjuvant chemotherapy in HER2-negative breast cancer--a substudy of the neoadjuvant GeparQuinto trial

Yasmin Issa-Nummer  1 , Silvia Darb-Esfahani, Sibylle Loibl, Georg Kunz, Valentina Nekljudova, Iris Schrader, Bruno Valentin Sinn, Hans-Ullrich Ulmer, Ralf Kronenwett, Marianne Just, Thorsten Kühn, Kurt Diebold, Michael Untch, Frank Holms, Jens-Uwe Blohmer, Jörg-Olaf Habeck, Manfred Dietel, Friedrich Overkamp, Petra Krabisch, Gunter von Minckwitz, Carsten Denkert
Affiliations
Clinical Trial

Prospective validation of immunological infiltrate for prediction of response to neoadjuvant chemotherapy in HER2-negative breast cancer--a substudy of the neoadjuvant GeparQuinto trial

Yasmin Issa-Nummer et al. PLoS One. .

Abstract

Introduction: We have recently described an increased lymphocytic infiltration rate in breast carcinoma tissue is a significant response predictor for anthracycline/taxane-based neoadjuvant chemotherapy (NACT). The aim of this study was to prospectively validate the tumor-associated lymphocyte infiltrate as predictive marker for response to anthracycline/taxane-based NACT.

Patients and methods: The immunological infiltrate was prospectively evaluated in a total of 313 core biopsies from HER2 negative patients of the multicenter PREDICT study, a substudy of the neoadjuvant GeparQuinto study. Intratumoral lymphocytes (iTuLy), stromal lymphocytes (strLy) as well as lymphocyte-predominant breast cancer (LPBC) were evaluated by histopathological assessment. Pathological complete response (pCR) rates were analyzed and compared between the defined subgroups using the exact test of Fisher.

Results: Patients with lymphocyte-predominant breast cancer (LPBC) had a significantly increased pCR rate of 36.6%, compared to non-LPBC patients (14.3%, p<0.001). LPBC and stromal lymphocytes were significantly independent predictors for pCR in multivariate analysis (LPBC: OR 2.7, p = 0.003, strLy: OR 1.2, p = 0.01). The amount of intratumoral lymphocytes was significantly predictive for pCR in univariate (OR 1.2, p = 0.01) but not in multivariate logistic regression analysis (OR 1.2, p = 0.11).

Conclusion: Confirming previous investigations of our group, we have prospectively validated in an independent cohort that an increased immunological infiltrate in breast tumor tissue is predictive for response to anthracycline/taxane-based NACT. Patients with LPBC and increased stromal lymphocyte infiltration have significantly increased pCR rates. The lymphocytic infiltrate is a promising additional parameter for histopathological evaluation of breast cancer core biopsies.

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Conflict of interest statement

Competing Interests: RK is employed by Sividon Diagnostics and FO is employed by Oncologianova. This does not alter the authors' adherence to the PLOS ONE policies on sharing data and materials.

Figures

Figure 1
Figure 1. CONSORT statement and workflow of the PREDICT study.
EC-T, epirubicin/cyclophosphamid followed by docetaxel; Pts, patients; pCR, pathologic complete response.
See this image and copyright information in PMC

References

    1. Estevez LG, Gradishar WJ (2004) Evidence-based use of neoadjuvant taxane in operable and inoperable breast cancer. Clin Cancer Res 10: 3249–3261 10.1158/1078-0432.CCR-03-0133 [doi];10/10/3249 [pii] - DOI - PubMed
    1. Kaufmann M, Hortobagyi GN, Goldhirsch A, Scholl S, Makris A, et al. (2006) Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: an update. J Clin Oncol 24: 1940–1949 24/12/1940 [pii];10.1200/JCO.2005.02.6187 [doi] - DOI - PubMed
    1. Smith IC, Heys SD, Hutcheon AW, Miller ID, Payne S, et al. (2002) Neoadjuvant chemotherapy in breast cancer: significantly enhanced response with docetaxel. J Clin Oncol 20: 1456–1466. - PubMed
    1. Fisher B, Bryant J, Wolmark N, Mamounas E, Brown A, et al. (1998) Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol 16: 2672–2685. - PubMed
    1. Houghton AN, Guevara-Patino JA (2004) Immune recognition of self in immunity against cancer. J Clin Invest 114: 468–471 10.1172/JCI22685 [doi] - DOI - PMC - PubMed

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