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Departments Surgery Gerontology and Geriatrics

FOCUS F emale breast cancer in the elderly; O ptimizing C linical guidelines US ing clinico-pathological and molecular data. Departments Surgery Gerontology and Geriatrics. Department of Surgery Department of Gerontology & Geriatrics

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Departments Surgery Gerontology and Geriatrics

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  1. FOCUSFemale breast cancer in the elderly; Optimizing Clinical guidelines USing clinico-pathological and molecular data • Departments • Surgery • Gerontology and Geriatrics Department of SurgeryDepartment of Gerontology & Geriatrics Prof. dr. C.J.H. van de Velde Prof. dr. R.G.J. Westendorp Dr. G.J. Liefers Dr. A.J.M. de Craen

  2. The Netherlands • Increase incidence breast cancer 2005-2025 18% • 40-50% of these patients are 65 years and older • 50-75% has comorbidity of any kind • No internationally agreed recommendations • Lack of clinical trial data • Uncertainty treatment toxicity and benefits • Interaction between therapy and comorbidity • Competing risks of death • New pathological and molecular variables associated with outcome and response to therapy • Lack of assessment tools to identify at-risk and frail elders in oncology FOCUS

  3. Giordano et al. JCO2005;4:783-91 Several cohort studies • Less aggressive therapy (corrected stage) • Strongly decreased survival (not only explained by therapy) • Stage at diagnosis higher • Tumor biology: increased hormone receptor positive, less Her2/neu overexpression, lower grades, lower proliferative indices • Life expectancy is central issue • However • Variability within age group is large (individualized treatment) • Comorbidity • Risks / benefits treatment FOCUS

  4. In conclusion • Increasing incidence of breast cancer in elderly However: • Limited data • No guidelines for individualized treatment Female breast cancer in the elderly; Optimizing clinical guidelines using clinico-pathological and molecular data FOCUS FOCUS

  5. Three parts FOCUS

  6. Observational study design • Integraal Kankercentrum West • Landelijk • Eurocare FOCUS

  7. Comprehensive Cancer Centre West • Selection • Female patients with breast cancer • 1999-2001 • 65 years and older FOCUS

  8. Registration form • Histopathology • Morfology, size, grade, TNM, etc • Receptors • Complications • Surgery • Radiotherapy • Chemotherapy (CTC) • Hormone therapy • Detection (screening / patient detected) • Treatment • Surgery • Radiotherapy • Adjuvant treatment • Unplanned change CT • Palliative treatment • Comorbidity • Charlson • Smoking • BMI • Results from the blood test • Geriatric parameters • Follow-up • Status • Recurrence • Treatment recurrence FOCUS

  9. Observational study design • IKW “documentatie studie” • Landelijk • Eurocare FOCUS

  10. Landelijke data 1994-2005 FOCUS

  11. Observational study design • IKW “documentatie studie” • Landelijk • Eurocare: data uit Europa FOCUS

  12. Three parts FOCUS

  13. Data from clinical trials EORTC 10902 Preoperative chemotherapy EORTC 10801 BCT vs Mastectomy Pooled dataset n=5500 (>65 years) EORTC 10854 Perioperative chemotherapy EORTC 22881 TEAM data FOCUS

  14. Trial data • Comparison of characteristics between the young and the elderly patients Selection of the elderly 2. Multivariate analysis Survival (OS, DSS, DFS) 3. Risk factors for the elderly - Morbidity - Frequency of Adverse Events - Treatment withdrawal 4. Age stratified analysis (65-74; 75-84 and 85 and older) within the elderly patients (age-dependent prediction model) FOCUS

  15. Three parts FOCUS

  16. Gene expression analyis • Recent studies no inclusion of elderly • Relevance of the signatures in elderly patients are unknown • Which factors are significantly different between young and elderly patients • Are there different activated pathways in young vs. elderly breast cancer patients • Validate existing and/or find new prognostic/predictive factors for elderly breast cancer patients FOCUS

  17. Central dogma of molecular biology • DNA in nucleus • Genes and non-coding regions • Gene: Introns and exons • Transcriptie DNA  RNA  Poly A tail, cap and splicing  mRNA • mRNA translated into protein in cytoplasm FOCUS

  18. Methods DNA SNP array • Infinium SNP array Illumina mRNA Expression array • Human WG6 expression array Illumina Protein Immunohistochemical staining on Tissue Micro Array (TMA) FOCUS

  19. Three parts Prospective study FOCUS

  20. Prospective study Combination of all data * Molecular data * Trial data * Data from cohorts Risk model - Recurrent disease - (Breast cancer related) death - Adverse events - Patient and tumor characteristics Evidence based, high quality care Tailored treatment guidelines FOCUS

  21. More information Esther Bastiaannet Heelkunde / Ouderengeneeskunde e.bastiaannet@lumc.nl 071-5265818 FOCUS

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