55
views
0
recommends
+1 Recommend
0 collections
    1
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      A clinically relevant gene signature in triple negative and basal-like breast cancer

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Introduction

          Current prognostic gene expression profiles for breast cancer mainly reflect proliferation status and are most useful in ER-positive cancers. Triple negative breast cancers (TNBC) are clinically heterogeneous and prognostic markers and biology-based therapies are needed to better treat this disease.

          Methods

          We assembled Affymetrix gene expression data for 579 TNBC and performed unsupervised analysis to define metagenes that distinguish molecular subsets within TNBC. We used n = 394 cases for discovery and n = 185 cases for validation. Sixteen metagenes emerged that identified basal-like, apocrine and claudin-low molecular subtypes, or reflected various non-neoplastic cell populations, including immune cells, blood, adipocytes, stroma, angiogenesis and inflammation within the cancer. The expressions of these metagenes were correlated with survival and multivariate analysis was performed, including routine clinical and pathological variables.

          Results

          Seventy-three percent of TNBC displayed basal-like molecular subtype that correlated with high histological grade and younger age. Survival of basal-like TNBC was not different from non basal-like TNBC. High expression of immune cell metagenes was associated with good and high expression of inflammation and angiogenesis-related metagenes were associated with poor prognosis. A ratio of high B-cell and low IL-8 metagenes identified 32% of TNBC with good prognosis (hazard ratio (HR) 0.37, 95% CI 0.22 to 0.61; P < 0.001) and was the only significant predictor in multivariate analysis including routine clinicopathological variables.

          Conclusions

          We describe a ratio of high B-cell presence and low IL-8 activity as a powerful new prognostic marker for TNBC. Inhibition of the IL-8 pathway also represents an attractive novel therapeutic target for this disease.

          Related collections

          Most cited references36

          • Record: found
          • Abstract: found
          • Article: found

          Stromal gene expression predicts clinical outcome in breast cancer.

          Although it is increasingly evident that cancer is influenced by signals emanating from tumor stroma, little is known regarding how changes in stromal gene expression affect epithelial tumor progression. We used laser capture microdissection to compare gene expression profiles of tumor stroma from 53 primary breast tumors and derived signatures strongly associated with clinical outcome. We present a new stroma-derived prognostic predictor (SDPP) that stratifies disease outcome independently of standard clinical prognostic factors and published expression-based predictors. The SDPP predicts outcome in several published whole tumor-derived expression data sets, identifies poor-outcome individuals from multiple clinical subtypes, including lymph node-negative tumors, and shows increased accuracy with respect to previously published predictors, especially for HER2-positive tumors. Prognostic power increases substantially when the predictor is combined with existing outcome predictors. Genes represented in the SDPP reveal the strong prognostic capacity of differential immune responses as well as angiogenic and hypoxic responses, highlighting the importance of stromal biology in tumor progression.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

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

            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.
              Bookmark
              • Record: found
              • Abstract: not found
              • Article: not found

              Gene-expression signatures in breast cancer.

                Bookmark

                Author and article information

                Journal
                Breast Cancer Res
                Breast Cancer Research : BCR
                BioMed Central
                1465-5411
                1465-542X
                2011
                6 October 2011
                : 13
                : 5
                : R97
                Affiliations
                [1 ]Department of Obstetrics and Gynecology, J. W. Goethe-University, Theodor-Stern-Kai 7, Frankfurt, 60590, Germany
                [2 ]Department of Obstetrics and Gynecology, University of Muenster, Albert-Schweitzer Straße 33, 48149, Muenster, Germany
                [3 ]Department of Breast Medical Oncology, The University of Texas M.D. Anderson Cancer Center, PO Box 301439, Houston, TX 77230-1439, USA
                [4 ]Department of Biology II, Ludwig-Maximilians-University Munich, Grosshaderner Str. 2, Planegg-Martinsried, 82152, Germany
                [5 ]Department of Obstetrics and Gynecology, J. Gutenberg-University, Langenbeckstr. 1, Mainz, 55131, Germany
                [6 ]Department of Obstetrics and Gynecology, University of Hamburg, Martinistrasse 52, Hamburg, 20246, Germany
                Article
                bcr3035
                10.1186/bcr3035
                3262210
                21978456
                1f20b5ec-4cba-413f-b77f-71fb8ca05a09
                Copyright ©2011 Rody et al.; licensee BioMed Central Ltd.

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Categories
                Research Article

                Oncology & Radiotherapy
                Oncology & Radiotherapy

                Comments

                Comment on this article