Title: Age interacts with the expression of steroid and HER-2 receptors in operable invasive breast cancer
Authors: Neven, Patrick ×
Van Calster, Ben
Vanden Bempt, Isabelle
Van Huffel, Sabine
Van Belle, Vanya
Hendrickx, Wouter
Decock, Julie
Wildiers, Hans
Paridaens, Robert
Amant, Frédéric
Leunen, Karin
Berteloot, Patrick
Timmerman, Dirk
Van Limbergen, Erik
Weltens, Caroline
Van den Bogaert, Walter
Smeets, Ann
Vergote, Ignace
Christiaens, Marie-Rose
Drijkoningen, Maria #
Issue Date: Jul-2008
Publisher: M. Nijhoff
Series Title: Breast Cancer Research and Treatment vol:110 issue:1 pages:153-159
Abstract: 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.
ISSN: 0167-6806
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Experimental Oncology
Gynaecological Oncology
ESAT - STADIUS, Stadius Centre for Dynamical Systems, Signal Processing and Data Analytics
Translational Cell & Tissue Research
Basic Research in Gynaecology Section (-)
Laboratory of Experimental Radiotherapy
Multidisciplinary Breast Clinic Section (-)
Surgical Oncology
× corresponding author
# (joint) last author

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