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Data driven derivation of cutoffs from a pool of 3,030 Affymetrix arrays to stratify distinct clinical types of breast cancer

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Abstract

Pooling of microarray datasets seems to be a reasonable approach to increase sample size when a heterogeneous disease like breast cancer is concerned. Different methods for the adaption of datasets have been used in the literature. We have analyzed influences of these strategies using a pool of 3,030 Affymetrix U133A microarrays from breast cancer samples. We present data on the resulting concordance with biochemical assays of well known parameters and highlight critical pitfalls. We further propose a method for the inference of cutoff values directly from the data without prior knowledge of the true result. The cutoffs derived by this method displayed high specificity and sensitivity. Markers with a bimodal distribution like ER, PgR, and HER2 discriminate different biological subtypes of disease with distinct clinical courses. In contrast, markers displaying a continuous distribution like proliferation markers as Ki67 rather describe the composition of the mixture of cells in the tumor.

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Acknowledgments

We thank Samira Adel and Katherina Kourtis for expert technical assistance and anonymous reviewers for their insightful suggestions. This work was supported by grants from the Deutsche Krebshilfe, the Margarete Bonifer-Stiftung, Bad Soden, the BANSS-Stiftung, Biedenkopf, and the Dr. Robert Pfleger-Stiftung, Bamberg. The efforts of the IGC and expO [31] are gratefully acknowledged.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, J. W. Goethe University, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany

    Thomas Karn, Eugen Ruckhäberle, Lars Hanker, Regine Gätje, Christine Solbach, Andre Ahr, Uwe Holtrich, Manfred Kaufmann & Achim Rody

  2. Department of Biology II, Ludwig-Maximilians-University, Munich, Germany

    Dirk Metzler

  3. Department of Obstetrics and Gynecology, Johannes Gutenberg University, Mainz, Germany

    Marcus Schmidt

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  1. Thomas Karn
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Correspondence to Thomas Karn.

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Karn, T., Metzler, D., Ruckhäberle, E. et al. Data driven derivation of cutoffs from a pool of 3,030 Affymetrix arrays to stratify distinct clinical types of breast cancer. Breast Cancer Res Treat 120, 567–579 (2010). https://doi.org/10.1007/s10549-009-0416-z

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