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

2. FOCUS 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

3. FOCUS 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 Giordano et al. JCO2005;4:783-91

4. 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

5. FOCUS Three parts

6. FOCUS Observational study design Integraal Kankercentrum West Landelijk Eurocare

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

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

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

10. FOCUS Landelijke data 1994-2005

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

12. FOCUS Three parts

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

14. FOCUS 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)

15. FOCUS Three parts

16. 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

17. 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

18. 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)

19. FOCUS Three parts Prospective study

20. 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

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