1. and why ?????????????

2. Breast cancer: -in the Netherlands 10.000 new cases/year -incidence has doubled since 1940, now 1000/10 6 women/year -30 % of all cancers in women -life time risk is 8-12% -in 50% of women with primary tumors occult metastases occur -death rate: 40% in node-negative 70% in node-positive nearly 100% in metastatic disease hereditary 5-10%, involvement BRCA-1, BRCA-2 and CHEK-2 in men: incidence 1% of that of women.

3. Hormonale behandeling bij borstkanker Remmers van de ER werking: Anti-oestrogenen borst bot endometrium endotheel SERM: tamoxifen – + + – selective ER modulatorraloxifen – + – – SERD ( selective ER downregulator) = full-anti-oestrogenen: ICI 182.780 (Faslodex=Fulvestrant) doet ER afbreken. Remmers van de oestrogeen aanmaak: Aromatase remmers Nonsteroidale: Anastrazole (Arimidex) en Letrozole (Femara) Steroidale : Exemestane(Aromasin)

6. Ligands and anti-estrogens

7. Endocrine treatment options of breast cancer After Robertson et al, EJC, 41, 346, 2005.

8. ER- ER+ tamoxifen treatment Fulvestrant, Aromatase inhibitors 100 70 effect of anti-estrogen treatment on recurrence in breast cancer recurrences tumor progressie veroorzaakt door genetische chaos

10. ER  -DESER  - raloxifene agonistantagonist cofactor

11. FRET Fluorescence Resonance Energy Transfer

13. Profile of anti-estrogen sensitivity by FRET sensitive insensitive resistant

15. Hypothetical scheme of anti-estrogenic treatment of breast cancer ER positive tumor truly positive tumor, ER dependent : or not chemotherapy PKAMAPK treatment tamoxifen ICI 163.384 or resveratrol fulvestrant raloxifene Individual treatment based on modification of the Estrogen Receptor

16. Acknowledgements Tumor Biology Alexander Griekspoor Wilbert Zwart Lennert Janssen Astrid Balkenende Desiree Verwoerd Els Groeneveld Jacques Neefjes Rob Michalides Clinic Sabine Linn Pathology Hans Peterse Elly Mesman Ellen Riem Statistics Harm van Tinteren FRET Kees Jalink Microarray Arno Floore Arno Velds Laura van ‘t Veer CLSM Lauran Oomen Lenny Brocks FACS Anita Pfauth Frank van Diepen Monoclonal Antibody Upstate Biotechnology Inc. Anti-estrogens Michel Renoir, Geneva Claude Labrie, Quebec Organon GSK