Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer - PubMed (original) (raw)

Clinical Trial

. 2010 Jan 1;28(1):105-13.

doi: 10.1200/JCO.2009.23.7370. Epub 2009 Nov 16.

Sibylle Loibl, Aurelia Noske, Marc Roller, Berit Maria Müller, Martina Komor, Jan Budczies, Silvia Darb-Esfahani, Ralf Kronenwett, Claus Hanusch, Christian von Törne, Wilko Weichert, Knut Engels, Christine Solbach, Iris Schrader, Manfred Dietel, Gunter von Minckwitz

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Clinical Trial

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

Carsten Denkert et al. J Clin Oncol. 2010.

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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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