PowerPoint Presentation - Netherlands Cancer Institute

and why ?????????????
Breast cancer:
-in the Netherlands 10.000 new cases/year
-incidence has doubled since 1940, now 1000/106 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.
Hormonale behandeling bij borstkanker
Remmers van de ER werking: Anti-oestrogenen
borst bot endometrium endotheel
SERM:
tamoxifen
–
+
+
–
selective ER modulator
raloxifen
–
+
–
–
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)
Hormonale regulatie van de borst
Oestrogenen
Progesteron
Voor de menopauze
LH/FSH
Ovarium
Hypofyse
Voor & na
de menopauze
ACTH
Bijnierschors
Androgenen
Oestrogenen
Progesteron
Omzetting
door aromatase
Hormonale interventies bij mammacarcinoom
Ovarium
LHRHagonist
Ovariële ablatie
Anti-oestrogeen
Progestageen
Hypofyse
Aromatase remmer
Bijnierschors
Enzym aromatase
Ligands and anti-estrogens
Endocrine treatment options of breast cancer
After Robertson et al, EJC, 41, 346, 2005.
tumor progressie veroorzaakt door
genetische chaos
100
ER70
ER+
recurrences
tamoxifen
treatment
Fulvestrant,
Aromatase
inhibitors
effect of anti-estrogen treatment
on recurrence in breast cancer
cofactor
ER-DES
agonist
ER- raloxifene
antagonist
FRET
Fluorescence Resonance
Energy Transfer
Profile of anti-estrogen sensitivity by FRET
insensitive
resistant
sensitive
Hypothetical scheme of anti-estrogenic treatment of breast cancer
ER positive tumor
truly positive tumor,
ER dependent :
PKA MAPK treatment
or not
chemotherapy
tamoxifen
fulvestrant
raloxifene
ICI 163.384 or resveratrol
Individual treatment based on modification of the
Estrogen Receptor
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
Anti-estrogens
Michel Renoir, Geneva
Claude Labrie, Quebec
Organon
GSK
CLSM
Lauran Oomen
Lenny Brocks
FACS
Anita Pfauth
Frank van Diepen
Monoclonal Antibody
Upstate Biotechnology Inc.