Haptoglobin phenotype is not a predictor of recurrence free survival in high-risk primary breast cancer patients

M.C. Gast, H. van Tinteren, M. Bontenbal, R.Q. van Hoesel, M.A. Nooij, S. Rodenhuis, P.N. Span, V.C. Tjan-Heijnen, E.E. de Vries, N. Harris, J.W.R. Twisk, J.H. Schellens, J.H. Beijnen

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Abstract

Background: Better breast cancer prognostication may improve selection of patients for adjuvant therapy. We conducted a retrospective follow-up study in which we investigated sera of high-risk primary breast cancer patients, to search for proteins predictive of recurrence free survival. Methods: Two sample sets of high-risk primary breast cancer patients participating in a randomised national trial investigating the effectiveness of high-dose chemotherapy were analysed. Sera in set I (n = 63) were analysed by surface enhanced laser desorption ionisation time-of-flight mass spectrometry (SELDI-TOF MS) for biomarker finding. Initial results were validated by analysis of sample set II (n = 371), using one-dimensional gel-electrophoresis. Results: In sample set I, the expression of a peak at mass-to-charge ratio 9198 (relative intensity 20), identified as haptoglobin (Hp) alpha-I chain, was strongly associated with recurrence free survival (global Log-rank test; p = 0.0014). Haptoglobin is present in three distinct phenotypes (Hp 1-1, Hp 2-1, and Hp 2-2), of which only individuals with phenotype Hp 1-1 or Hp 2-1 express the haptoglobin alpha-1 chain. As the expression of the haptoglobin alpha-1 chain, determined by SELDI-TOF MS, corresponds to the phenotype, initial results were validated by haptoglobin phenotyping of the independent sample set II by native one-dimensional gel-electrophoresis. With the Hp 1-1 phenotype as the reference category, the univariate hazard ratio for recurrence was0.87 (95% CI: 0.56-1.34, p = 0.5221) and 1.03 (95% CI: 0.65-1.64, p = 0.8966) for the Hp 2-1 and Hp 2-2 phenotypes, respectively, in sample set II. Conclusion: In contrast to our initial results, the haptoglobin phenotype was not identified as a predictor of recurrence free survival in high-risk primary breast cancer in our validation set. Our initial observation in the discovery set was probably the result of a type I error (i.e. false positive). This study illustrates the importance of validation in obtaining the true clinical applicability of a potential biomarker.
Original languageEnglish
Pages (from-to)389-389
JournalBMC Cancer
Volume8
DOIs
Publication statusPublished - 1 Jan 2008

Cite this

Gast, M. C., van Tinteren, H., Bontenbal, M., van Hoesel, R. Q., Nooij, M. A., Rodenhuis, S., Span, P. N., Tjan-Heijnen, V. C., de Vries, E. E., Harris, N., Twisk, J. W. R., Schellens, J. H., & Beijnen, J. H. (2008). Haptoglobin phenotype is not a predictor of recurrence free survival in high-risk primary breast cancer patients. BMC Cancer, 8, 389-389. https://doi.org/10.1186/1471-2407-8-389