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Keeping Data Continuous when Analyzing the Prognostic Impact of a Tumor Marker: An Example with Cathepsin D in Breast Cancer

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Abstract

The prognostic value of cathepsin D has been recently recognized, but as many quantitative tumor markers, its clinical use remains unclear partly because of methodological issues in defining cut-off values. Guidelines have been proposed for analyzing quantitative prognostic factors, underlining the need for keeping data continuous, instead of categorizing them. Flexible approaches, parametric and non-parametric, have been proposed in order to improve the knowledge of the functional form relating a continuous factor to the risk. We studied the prognostic value of cathepsin D in a retrospective hospital cohort of 771 patients with breast cancer, and focused our overall survival analysis, based on the Cox regression, on two flexible approaches: smoothing splines and fractional polynomials. We also determined a cut-off value from the maximum likelihood estimate of a threshold model. These different approaches complemented each other for (1) identifying the functional form relating cathepsin D to the risk, and obtaining a cut-off value and (2) optimizing the adjustment for complex covariate like age at diagnosis in the final multivariate Cox model. We found a significant increase in the death rate, reaching 70% with a doubling of the level of cathepsin D, after the threshold of 37.5 pmol mg−1. The proper prognostic impact of this marker could be confirmed and a methodology providing appropriate ways to use markers in clinical practice was proposed.

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Authors and Affiliations

  1. Service de Biostatistique des Hospices Civils de Lyon, Université Claude Bernard, Centre Hospitalier Lyon Sud, Pierre-Benite, France

    N. Bossard, L. Berrerd & J. Estève

  2. Service de Techniques Nucléaires & Biophysiques, Unité In Vitro, Centre Hospitalier Lyon Sud, Pierre-Benite, France

    F. Descotes & Y. Barbier

  3. Service de Chirurgie, Centre Léon Bérard, Lyon, France

    A.G. Bremond

  4. Service de Chirurgie Oncologique, Centre Hospitalier Lyon Sud, Pierre-Benite, France

    Y. Bobin

  5. Service de Gynécologie Obstetrique, Hôpital de la Croix Rousse, Lyon, France

    P. De Saint Hilaire

  6. Service de Gynécologie Obstétrique, Hôpital de l'Hôtel-Dieu, Lyon, France

    F. Golfier

  7. Clinique Jeanne d'Arc, Lyon, France

    A. Awada

  8. Service de Gynécologie, Pavillon L, Hôpital Edouard Herriot, Lyon, France

    P.M. Mathevet

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  1. N. Bossard
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Bossard, N., Descotes, F., Bremond, A. et al. Keeping Data Continuous when Analyzing the Prognostic Impact of a Tumor Marker: An Example with Cathepsin D in Breast Cancer. Breast Cancer Res Treat 82, 47–59 (2003). https://doi.org/10.1023/B:BREA.0000003919.75055.e8

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