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St. Gallen 2007. Consensusmeeting P. Berteloot. First select the target : better choice of adjuvant treatments for breast cancer patients St Gallen 2005. 1 Target = endocrine sensivity (low – intermediate -high) 2 defining the riskgroups (low – intermediate- high).
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St. Gallen 2007 Consensusmeeting P. Berteloot
First select the target : better choice of adjuvant treatments for breast cancer patientsSt Gallen 2005 • 1 Target = endocrine sensivity (low – intermediate -high) • 2 defining the riskgroups (low – intermediate- high)
Break-throughs since 2005 • Herceptin! • Confirmation A.I. • Lower threshold for Taxanes
Present Problems • Past trials : large but not selective • General conclusions • Possibly not suitable for all subgroups • Not pre-planned subgroup analysis are statistically not reliable
Need for • Inclusion criteria for future trials should be selective for important targets • Individualised therapy should be based on reliable and selective tumor information • Pitfalls of diagnostic procedures • DCIS ~ micro-invasion • Passive transportation of malignant cells -> axilla • Error rate in HR assessement • Depending on different kits • Fixation • Eroor rate in HER2 status Viale G.
Importance of local control by surgery and Radiotherapy Improved local control at 5 years of follow-up Proportional survival benefit at 15 years of follow-up Ratio 4:1
Important highlights of St Gallen 2007 • MRI staging in breastcancer • Ipsilateral : 15-20 % • Contralateral : 3-5 % • Independent of : • Age • Pathology • Mammographic density C. Kuhl NEJM
Breast surgery in advanced breast cancer • Regained importance due to : • Better and longer control of distant disease • Ability of detecting small metastatic foci Large retrospective reviews of patients treated by surgical resection of the primary tumor to clear borders have demonstrated longer survival
Predictive factors for chemosensitivity • TOPO II • Sensitivity for anthracyclines • Gene level ~ protein level if proliferation index ( KI67) is elevated • Taxanes • Tau-protein • HER2 pos ? • P-53 mutations
Predictive factors for chemosensitivity • Alkylantia Platinum • ER positive < 35 years HER2 signaling DNA Damaging Agents in BRCA1 patients worse prognosis
Association HER2 – ER-pos • Chances of finding HER2 positivity associated with ER-positivity is higher in young than in older women
Herceptin • Update Hera-trial • 2 years of follow-up • 1 year of Herceptin • DFS : 6,3 % • OS : 2,7 % • Compairable gain for all subgroups • 2 important questions • Sequencing ? • Duration of therapy ? absolute gain
Consensus issues concerning Herceptin • Chemo in Her2 positive patients • Dependent on receptor status : 60 % yes • Anthracyclines to all : 73 % yes • Taxanes to all : 43 % yes • 6 to 8 cycles : 63 % yes
Chemotherapy schedules in HER2 + • CAF ~ CEF : 62 % yes • AC-T : 32 % yes • FEC : 32 % yes • TAC : 30 % yes • FEC-TAX : 32 % yes • TAX + carbo : 51 % yes The opinions are very devided
Sequencing Herceptin-Chemotherapy • Sequential : 38 % • Concommittant : 40 % • No preference : 22 %
Duration of Herceptin administration • Shorter in elderly : 51 % yes • Shorter for node neg : 38 % yes • Is duration riskdependent : 40 % yes • Importance of early onset : 60 % yes • 12 months : 91 % yes • 9 weeks + Docetaxel : 14 % yes • 2 years : ?
Herceptin indications • IHC +++ : 92 % • FISH requested : 15 % yes • T<1 cm Node neg : 56 % yes Receptor neg • Tx node neg : 58 % yes Receptor pos independent of node and receptorstatus
Safety of Herceptin • Avoid low LVEF ( 50-55) : 74 % yes • > 70 years : 30 % yes • Preventive use of ace inhibitors : 7 % yes
Hormonal therapy Postmenopausal consensus topics • Tam alone • Node neg : 50 % • Node pos : / • High ER-PR : 54 % • HER2 neg : 52 %
Hormonal therapy Postmenopausal consensus topics • AI upfront • In all patients : 19 % yes • High risk : 65 % yes • HER2 pos : 66 % yes • HER2 neg : 33 % yes
Hormonal therapy Postmenopausal consensus topics • If started with TAM Switch all : 50 % yes After 2 to 3 years : 89 % yes After 5 years : 60 % yes Only for TAM-intolerance : 65 % yes
Preference • AI upfront : 31 % • TAM AI : 63 % • TAM x 5 : 5,7 %
After 5 years of TAM AI • All : 84 % yes • Node pos : 92 % yes • HER2 neg : 40 % yes • HER2 pos : 74 % yes
Total duration of hormonal therapy • 5 years : 58 % • 5 to 10 years : 75 % • > 10 years : ? • Life-time for high-risk patients :37 %
Evaluation ovarian function at the start of AI • By onset : 55 % yes • After 6 to 12 weeks : 48 % yes
Supportive care + AI • Ca + Vit D : 61 % yes • Bifosfanates for all : 3 % • Fysical exercise : 100 % • BMC : 88 %
Pre-menopausal : consensus topics • TAM alone is an option : 92 % yes • OFS + TAM is an option : 83 % yes • OFS alone • For everyone : 7 % yes • For low risk : 32 % yes
Modality of ovarian suppression • LHRH analogue : 100 % • Surgery : 76 % • Radiotherapy : 19 % • Depending on age and : 75 % histological subtype
Duration of ovarian suppression • 2 years for all : 29 % • 2 years node negative : 43 % node positive • 5 years node positive : 66 % HER2 positive • 5 years for all : 25 % • Individualisation : 79 %
Chemo + OFS • Concurrently : 30 % • Sequentially : 82 % • Concurrently to preserve : 65 % fertility
OFS + AI • All : 6 % • Contra-indication for Tam : 68 % • Trials : 54 %
AI : timing attempt to conclusions • Upfront : patients with high risk for early relapse • High tumorload : T2 ; N2 • Biological agressiveness • gr III • HER2 pos • vascular invasion • Negative hormone receptor status Mauriac, Ann Oncol
AI : timing • Switch after 2-3 years : intermediate risk • Adjuvant hormonal therapy ≥ 5 years • Relapse curve receptor positive patients • Increased benefit ~ duration extended adjuvant therapy
Long-Term Risk of Breast Cancer Recurrence Remains High in ER+ Patients 0.3 ER+ (n=2257) ER– (n=1305) 0.2 Recurrence hazard rate 0.1 0 0 1 2 3 4 5 6 7 8 9 10 11 12 Years Saphner et al. J Clin Oncol. 1996;14:2738.
Annual Risk of Recurrence by Nodal Status • The risk of late recurrence remains substantial even in patientswith node-negative tumors 0.3 N0 N1-3 N4+ 0.2 Recurrence hazard rate 0.1 0 0 1 2 3 4 5 6 7 8 9 10 11 12 Years Saphner et al. J Clin Oncol. 1996;14:2738.
Benefit of TAM +/- OS • No clear evidence found ! N. Davidson • No large prospective randomised trials available • Actual SOFT trial and TEXT trial • Meta-analysis by Jack Cuzick • Limited benefit likely • Age dependent ?
Chemotherapy • Hormone sensitivity indicate : • the additional gain of chemotherapy eg postmenopausal patients : hormone receptor positive 3 % and hormone receptor negative 8% • Preference of schedule • No consensus at all • Tendency to be more aggressive in HR neg en HER2 pos patients • HER2 Status
Incorporation of taxanes • Only trials in node pos patients 3 – 7 % gain • Level 1 evidence ? • Only PACS 01 has an optimal control arm • PACS 01: imbalance of ER status and unexplained age difference • Dependent on: • Hormone receptor status • HER2 positivity ?
Conclusion St. Gallen 2007 • No consensus yet • We don’t expect large changes in our home strategy