PLoS ONE (Jan 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,
  • 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

DOI
https://doi.org/10.1371/journal.pone.0079775
Journal volume & issue
Vol. 8, no. 12
p. e79775

Abstract

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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.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.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).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.