title: Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer.
abstract: PURPOSE Preclinical data suggest a contribution of the immune system to chemotherapy response. In this study, we investigated the prespecified hypothesis that the presence of a lymphocytic infiltrate in cancer tissue predicts the response to neoadjuvant chemotherapy. METHODS We investigated intratumoral and stromal lymphocytes in a total of 1,058 pretherapeutic breast cancer core biopsies from two neoadjuvant anthracycline/taxane-based studies (GeparDuo, n = 218, training cohort; and GeparTrio, n = 840, validation cohort). Molecular parameters of lymphocyte recruitment and activation were evaluated by kinetic polymerase chain reaction in 134 formalin-fixed, paraffin-embedded tumor samples. Results In a multivariate regression analysis including all known predictive clinicopathologic factors, the percentage of intratumoral lymphocytes was a significant independent parameter for pathologic complete response (pCR) in both cohorts (training cohort: P = .012; validation cohort: P = .001). Lymphocyte-predominant breast cancer responded, with pCR rates of 42% (training cohort) and 40% (validation cohort). In contrast, those tumors without any infiltrating lymphocytes had pCR rates of 3% (training cohort) and 7% (validation cohort). The expression of inflammatory marker genes and proteins was linked to the histopathologic infiltrate, and logistic regression showed a significant association of the T-cell-related markers CD3D and CXCL9 with pCR. CONCLUSION The presence of tumor-associated lymphocytes in breast cancer is a new independent predictor of response to anthracycline/taxane neoadjuvant chemotherapy and provides useful information for oncologists to identify a subgroup of patients with a high benefit from this type of chemotherapy.
authors.affiliation: Institute of Pathology, Charité Hospital, Campus Mitte, Schumannstr 20/21, D-10117 Berlin, Germany. carsten.denkert@charite.de
authors.forename: Carsten
authors.initials: C
authors.lastname: Denkert
authors.forename: Sibylle
authors.initials: S
authors.lastname: Loibl
authors.forename: Aurelia
authors.initials: A
authors.lastname: Noske
authors.forename: Marc
authors.initials: M
authors.lastname: Roller
authors.forename: Berit Maria
authors.initials: BM
authors.lastname: Müller
authors.forename: Martina
authors.initials: M
authors.lastname: Komor
authors.forename: Jan
authors.initials: J
authors.lastname: Budczies
authors.forename: Silvia
authors.initials: S
authors.lastname: Darb-Esfahani
authors.forename: Ralf
authors.initials: R
authors.lastname: Kronenwett
authors.forename: Claus
authors.initials: C
authors.lastname: Hanusch
authors.forename: Christian
authors.initials: C
authors.lastname: von Törne
authors.forename: Wilko
authors.initials: W
authors.lastname: Weichert
authors.forename: Knut
authors.initials: K
authors.lastname: Engels
authors.forename: Christine
authors.initials: C
authors.lastname: Solbach
authors.forename: Iris
authors.initials: I
authors.lastname: Schrader
authors.forename: Manfred
authors.initials: M
authors.lastname: Dietel
authors.forename: Gunter
authors.initials: G
authors.lastname: von Minckwitz
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D017252:CD3 Complex / Q000032:analysis; D054370:Chemokine CXCL9 / Q000032:analysis; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology*; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011446:Prospective Studies
chemical_list: D017252:CD3 Complex; C472562:CD3delta antigen; C080810:CXCL9 protein, human; D054370:Chemokine CXCL9