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      Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer.

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          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.

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          Author and article information

          Journal
          J. Clin. Oncol.
          Journal of clinical oncology : official journal of the American Society of Clinical Oncology
          American Society of Clinical Oncology (ASCO)
          1527-7755
          0732-183X
          Jan 01 2010
          : 28
          : 1
          Affiliations
          [1 ] Institute of Pathology, Charité Hospital, Campus Mitte, Schumannstr 20/21, D-10117 Berlin, Germany. carsten.denkert@charite.de
          Article
          JCO.2009.23.7370
          10.1200/JCO.2009.23.7370
          19917869

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