hormonale adjuvante behandeling van mammacarcinoom onder de veertig
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Hormonale adjuvante behandeling van mammacarcinoom onder de veertig. Jan H. Schornagel Nederlands Kanker Instituut- Antoni van Leeuwenhoek Ziekenhuis Amsterdam, 28-6-2006. Hormonale adjuvante behandeling van mammacarcinoom onder de veertig. Indicaties Keuze van therapie Bijwerkingen - PowerPoint PPT PresentationTRANSCRIPT
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Hormonale adjuvante behandeling van mammacarcinoom onder de veertig
Jan H. Schornagel
Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis
Amsterdam, 28-6-2006
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Hormonale adjuvante behandeling van mammacarcinoom onder de veertig
• Indicaties• Keuze van therapie• Bijwerkingen• Specifieke problemen
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Hormonale adjuvante behandeling van mammacarcinoom onder de veertig
• Indicaties• Keuze van therapie• Bijwerkingen• Specifieke problemen
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Onafhankelijke Risicofactoren
• Tumorgrootte• Gradering volgens Bloom en Richardson• N+• Leeftijd 35
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Indicaties adjuvante hormonale therapie onder de 40
• Uitsluitend indien ER+ en/of PgR+• N+ tumoren• N- én 1 cm én SBR II of III én 35 jaar• N- én 1 cm én 35 jaar• N- én 1-2 cm én SBR III • N- én 2-3 cm SBR II of III • N- én 3 cm
Richtlijn Behandeling van het Mammacarcinoom 2005
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Hormonale adjuvante behandeling van mammacarcinoom onder de veertig
• Indicaties• Keuze van therapie• Bijwerkingen• Specifieke problemen
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Hormonale adjuvante therapie bij premenopauzale vrouwen
1. Tamoxifen2. LHRH analoga3. LHRH analoga + Tamoxifen
Richtlijn Behandeling van het Mammacarcinoom 2005
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Copyright © American Society of Clinical Oncology
Fig 2. Overall survival stratified by study
Klijn, J. G.M. et al. J Clin Oncol; 19:343-353 2001
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Op basis van deze gegevens wordt tegenwoordig tamoxifen vrijwel standaard gecombineerd met een LHRH agonist in de adjuvante hormonale behandeling van premenopauzale vrouwen.
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Is dat wel “evidence based medicine”?
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Nee, er is hooguit “circumstantial evidence”
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Adjuvant goserelin in pre-menopausal patients with early breast cancer: Results from the ZIPP study.
M. Baum, A. Hackshaw, J. Houghton, L.E. Rutqvist, B. Nordenskold, A. Nicolucci, R. Sainsbury, ZIPP International Collaborators Group
European Journal of Cancer 2006;42:895-904
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The ZIPP (Zoladex In Premenopausal Patients) study was designed to determine whether addition of goserelin and/or tamoxifen to adjuvant therapy (radiotherapy and/or chemotherapy), provided benefit to pre- or peri-menopausal women with operable, early breast cancer. Between 1987 and 1999 a total of 2710 patients were recruited from the four trial groups (CRUK, Stockholm, SE Sweden, GIVIO).
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Fig. 1 The distribution of patients in the ZIPP trial (n=2710)
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ZIPP study: Kaplan-Meier curves of overall survival
M.Baum et al. Eur J Cancer (2006) 42:895-904
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ZIPP Trial: Conclusion
“The effect on survival was similar in patients who received tamoxifen only and those receiving goserelin only. There was insufficient evidence to conclude whether the effect of the two treatments combined was associated with a greater survival.”
M. Baum, et al. Eur J Cancer 2006;42:895-904
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Major reported side-effects in the CRUK trial Tamox Zoladex+TamoxN = 463 N = 457
Hot flushes 78 (17) 200 (44)Weight gain 32 (7) 50 (11)Tiredness 10 (2) 12 (3)Headache 5 (1) 21 (5)Pain 9 (2) 11 (3)Nausea/vomiting 0 (0) 4 (<1)Bone pain/arthralgia 4 (1) 11 (2)Anxiety/depression/irritability 10 (2) 26 (6)Sweating 5 (1) 23 (5)
Patients with > 1 side effect 189 (41) 297 (65)
M. Baum et al. Eur J Cancer 2006;42:895-904
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De moraal van het verhaal……
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IBCSG 24-02: SOFT
Premeno.
ER 10% and/orPgR 10%
Patients who continue to be“premenopausal”either after CT or without CT
CT=chemotherapy; T=tamoxifen; E=exemestane; OFS=ovarian function suppression using GnRH analoguex 5 years or bilateral oophorectomy or radiation
RANDOMIZE
T x 5y
OFS + T x 5y
OFS + E x 5y
Any CT
Premenopausal
No CT
Strata
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Hormonale adjuvante behandeling van mammacarcinoom onder de veertig
• Indicaties• Keuze van therapie• Bijwerkingen• Specifieke problemen
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Side effects of endocrine adjuvant therapy in premenopausal women (1)
• Vasomotor symptoms• Vaginal dryness• Sexual dysfunction• Vaginal discharge• Changes in body image• Cognitieve stoornissen• Anxiety and depressive symptoms
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Side effects of endocrine adjuvant therapy in premenopausal women (2)
Chemical castration with LHRH analogs was associated with the highest level of menopausal symptoms; the effect of tamoxifen was found to be slower and milder. Vasomotor symptoms and vaginal dryness were the most troublesome side effects. Most symptoms were reversible.
M Nystedt et al. J Clin Oncol 2003;21:1836
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Major reported side-effects in the CRUK trial Tamox Zoladex+TamoxN = 463 N = 457
Hot flushes 78 (17) 200 (44)Weight gain 32 (7) 50 (11)Tiredness 10 (2) 12 (3)Headache 5 (1) 21 (5)Pain 9 (2) 11 (3)Nausea/vomiting 0 (0) 4 (<1)Bone pain/arthralgia 4 (1) 11 (2)Anxiety/depression/irritability 10 (2) 26 (6)Sweating 5 (1) 23 (5)
Patients with > 1 side effect 189 (41) 297 (65)
M. Baum et al. Eur J Cancer 2006;42:895-904
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Treatment of hot flushes
• Vitamin E 800 IU/day• Clonidine 25-50 μg a.n.• Venlafaxine 375.5-75 mg/day• Paroxetine 20 mg/day• Gabapentine 900 mg/day
None of these is very effective
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Hormonale adjuvante behandeling van mammacarcinoom onder de veertig
• Indicaties• Keuze van therapie• Bijwerkingen• Specifieke problemen
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Specifieke problemen
• Optimale duur hormonale therapie• Optimale duur LHRH analoga• Switch na 2½ jaar• Verlies van botmassa• Vaginale oestrogenen veilig?
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Aanbevelingen tav potentieel verlies van botmassa
• Calciuminname ( 1000 mg/dag)• Adequate vit. D status• Voldoende lichaamsbeweging• Bij hoog risico BMD meting• Eventueel bisfosfonaat (2-5 jaar)
Richtlijn Behandeling van het Mammacarcinoom 2005
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Kendall, A. et al. Ann Oncol 2006 17:584-587
Figure 1: Serum E2 levels in women receiving concurrent aromatase inhibitors and vaginal estradiol.
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