Outcome and Human Epithelial Growth Factor Receptor (HER) 1-4 status in invasive breast carcinomas with proliferation indices evaluated using bromodeoxyuridine (BrdU) labelling

Autor: J.R. Reeves, Peter Stanton, S. Tovey, Caroline J Witton, John M. S. Bartlett, Timothy G. Cooke
Rok vydání: 2004
Předmět:
Oncology
Receptor
ErbB-4
Receptor
ErbB-3
Receptor
ErbB-2
Cohort Studies
chemistry.chemical_compound
Surgical oncology
Antineoplastic Combined Chemotherapy Protocols
Medicine
Doubling time
Life Tables
skin and connective tissue diseases
Mastectomy
Medicine(all)
Carcinoma
Ductal
Breast
Middle Aged
Prognosis
Combined Modality Therapy
bromodeoxyuridine
Neoplasm Proteins
ErbB Receptors
Treatment Outcome
Lymphatic Metastasis
Immunohistochemistry
Female
Cell Division
Bromodeoxyuridine
Research Article
medicine.drug
Adult
medicine.medical_specialty
Antineoplastic Agents
Hormonal
Breast Neoplasms
breast cancer
Breast cancer
Growth factor receptor
HER3
HER2
Internal medicine
HER1
Humans
Neoplasm Invasiveness
HER4
Survival analysis
Aged
Proportional Hazards Models
business.industry
medicine.disease
Survival Analysis
Tamoxifen
chemistry
business
Follow-Up Studies
Zdroj: Breast Cancer Research
ISSN: 1465-542X
Popis: Background We have shown previously that whereas overexpression of human epidermal growth factor receptor (HER)1, HER2 and HER3 is associated with poor prognosis in breast cancer, HER4 is associated with a good prognosis. Cell proliferation is a key component of aggressive cancers and is driven by growth factors. In this study, bromodeoxyuridine (BrdU)-derived proliferation indices are correlated with clinical outcome and HER1–4 status for further clarification of the differing roles for the HER family at a biological level. Methods Seventy-eight invasive breast cancers had BrdU labelling in vivo to determine the BrdU labelling index (BLI) and the potential tumour doubling time (Tpot). Long-term clinical follow-up was available for these patients. We used immunohistochemistry to establish the HER1–4 status in 55 patients from the BrdU cohort. Results We demonstrate a significant correlation between high BLI values and breast cancer-specific death (P = 0.0174). Low Tpot times were also significantly correlated with breast cancer-specific death (P = 0.0258). However, BLI did not independently predict survival in Cox's multiple regression analysis when combined with other prognostic factors such as size, grade and nodal status. Tumours found to be positive for HER1, HER2 or HER3 had significantly (P = 0.041) higher labelling indices, with HER1 also showing significantly higher indices when considered independently (P = 0.024). Conversely, HER4 positivity was significantly correlated (P = 0.013) with low BLI values, in line with previous data associating this receptor with good prognosis tumours. Conclusions These results support the hypothesis that HER1–3 are associated with driving tumour proliferation, whereas HER4 is involved in a non-proliferative or even protective role.
Databáze: OpenAIRE
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