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FOCUS Female breast cancer in the elderly; Optimizing Clinical guidelines USing clinico-pathological and molecular data Departments Department of Surgery - Surgery Prof. dr. C.J.H. van de Velde - Gerontology and Geriatrics Dr. G.J. Liefers Department of Gerontology & Geriatrics Prof. dr. R.G.J. Westendorp Dr. A.J.M. de Craen 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 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 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 Three parts FOCUS Observational study design • Integraal Kankercentrum West • Landelijk • Eurocare FOCUS Comprehensive Cancer Centre West Selection - Female patients with breast cancer - 1999-2001 - 65 years and older FOCUS Registration form • Histopathology • Complications • Morfology, size, grade, TNM, etc •Surgery • Receptors •Radiotherapy •Chemotherapy (CTC) •Detection (screening / patient detected) •Hormone therapy • Treatment Comorbidity •Charlson •Smoking • Surgery • Follow-up •BMI • Status •Results from the blood test • Recurrence •Geriatric parameters FOCUS • Treatment recurrence • Radiotherapy • Adjuvant treatment • Unplanned change CT • Palliative treatment Observational study design • IKW “documentatie studie” • Landelijk • Eurocare FOCUS Landelijke data 1994-2005 FOCUS Observational study design • IKW “documentatie studie” • Landelijk • Eurocare: data uit Europa FOCUS Three parts FOCUS Data from clinical trials EORTC 10902 Preoperative chemotherapy EORTC 10801 BCT vs Mastectomy EORTC 10854 Perioperative chemotherapy EORTC 22881 TEAM data FOCUS Pooled dataset n=5500 (>65 years) Trial data 1.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 Three parts FOCUS 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 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 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 Three parts Prospective study FOCUS 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 More information Esther Bastiaannet Heelkunde / Ouderengeneeskunde [email protected] 071-5265818 FOCUS