title: Prospective validation of immunological infiltrate for prediction of response to neoadjuvant chemotherapy in HER2-negative breast cancer--a substudy of the neoadjuvant GeparQuinto trial.
abstract: BACKGROUND
  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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors: German Breast Group, Neu-Isenburg, Germany.
authors: Yasmin
authors: Y
authors: Issa-Nummer
authors: Silvia
authors: S
authors: Darb-Esfahani
authors: Sibylle
authors: S
authors: Loibl
authors: Georg
authors: G
authors: Kunz
authors: Valentina
authors: V
authors: Nekljudova
authors: Iris
authors: I
authors: Schrader
authors: Bruno Valentin
authors: BV
authors: Sinn
authors: Hans-Ullrich
authors: HU
authors: Ulmer
authors: Ralf
authors: R
authors: Kronenwett
authors: Marianne
authors: M
authors: Just
authors: Thorsten
authors: T
authors: Kühn
authors: Kurt
authors: K
authors: Diebold
authors: Michael
authors: M
authors: Untch
authors: Frank
authors: F
authors: Holms
authors: Jens-Uwe
authors: JU
authors: Blohmer
authors: Jörg-Olaf
authors: JO
authors: Habeck
authors: Manfred
authors: M
authors: Dietel
authors: Friedrich
authors: F
authors: Overkamp
authors: Petra
authors: P
authors: Krabisch
authors: Gunter
authors: G
authors: von Minckwitz
authors: Carsten
authors: C
authors: Denkert
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000401:mortality / Q000473:pathology; D001952:Bridged-Ring Compounds / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000276:immunology / Q000473:pathology; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids / Q000008:administration & dosage
chemical_list: D018943:Anthracyclines; D001952:Bridged-Ring Compounds; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; C080625:taxane; C508053:ERBB2 protein, human