Age interacts with the expression of steroid and HER-2 receptors in operable invasive breast cancer

P. Neven, B. Van Calster, I. Van Den Bempt, S. Van Huffel, V. Van Belle, W. Hendrickx, J. Decock, H. Wildiers, R. Paridaens, F. Amant, K. Leunen, P. Berteloot, D. Timmerman, E. Van Limbergen, C. Weltens, W. Van Den Bogaert, A. Smeets, I. Vergote, M. R. Christiaens, M. Drijkoningen

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11 Citations (Scopus)


Background: The negative association between the oestrogen receptor (ER) and the human epidermal growth factor receptor 2 (HER-2) in breast cancer travels in both directions. ER+ tumours are less likely HER-2 + and HER-2+ tumours are less likely ER+. Methods: We studied the age-related immunohistochemical (IHC) expression of ER, progesterone receptor (PR) and HER-2 in 2,227 tumours using age as a continuous variable. Steroid receptors were considered positive for any nuclear staining of invasive cancer cells and for HER-2, either for strong expression by IHC (score 3+) or gene amplification by fluorescence in situ hybridisation (FISH). Based on nonparametric regression, the age-related association between steroid receptors and HER-2 was presented as likelihood curves. Results: The association between ER or PR and HER-2 is age-related. The age-related expression of ER and PR is HER-2 dependent. In HER-2- cases, the odds ratio (OR) for being ER+ was 2.594 (95% CI = 1.874-3.591) up to age 50 and age-independent thereafter; for PR-expression the OR was 2.687 (95% CI = 1.780-4.057) up to age 45 and 0.847 (95% CI = 0.761-0.942) thereafter. In HER-2+ cases, the OR was 0.806 (95% CI = 0.656-0.991) to be ER + and 0.722 (95% CI = 0.589-0.886) to be PR+. The age-related OR for breast cancers to be HER-2+ is steroid receptor dependent. Taking together, ER+PR+HER-2+ breast cancers appear on average 5.4 years earlier than breast cancers of any other ER/PR/HER-2 phenotype (95% CI = 3.3-7.5; P < 0.0001). Conclusion: There is a qualitative interaction between age and expression of steroid and HER-2 receptors. Our findings suggest a strong age-related selective growth advantage for breast tumour cells belonging to the ER+PR+HER-2 + subgroup.

Original languageEnglish
Pages (from-to)153-159
Number of pages7
JournalBreast Cancer Research and Treatment
Issue number1
Publication statusPublished - 1 Jul 2008



  • Breast cancer
  • Hormone receptors
  • Human epidermal growth factor receptor 2
  • Interaction

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Neven, P., Van Calster, B., Van Den Bempt, I., Van Huffel, S., Van Belle, V., Hendrickx, W., Decock, J., Wildiers, H., Paridaens, R., Amant, F., Leunen, K., Berteloot, P., Timmerman, D., Van Limbergen, E., Weltens, C., Van Den Bogaert, W., Smeets, A., Vergote, I., Christiaens, M. R., & Drijkoningen, M. (2008). Age interacts with the expression of steroid and HER-2 receptors in operable invasive breast cancer. Breast Cancer Research and Treatment, 110(1), 153-159.