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


CONCLUSIONS
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.
Department of Obstetrics and Gynaecology, Multidisciplinary Breast Centre, University Hospitals Leuven, Herestraat 49, B-3000 Leuven, Belgium. Patrick.neven@uz.kuleuven.ac.be
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Neven
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Van Calster
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Van den Bempt
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Van Huffel
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Van Belle
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Hendrickx
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Decock
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Wildiers
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Paridaens
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Amant
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Leunen
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Berteloot
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Timmerman
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Van Limbergen
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Weltens
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Van den Bogaert
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Smeets
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Vergote
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Christiaens
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Drijkoningen
D000328:Adult; D000368:Aged; D000375:Aging; D001943:Breast Neoplasms / Q000737:chemistry*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D011960:Receptors, Estrogen / Q000032:analysis*; D011980:Receptors, Progesterone / Q000032:analysis*
D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human