st. gallen 2007
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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). - PowerPoint PPT PresentationTRANSCRIPT
St. Gallen 2007St. Gallen 2007
Consensusmeeting Consensusmeeting
P. BertelootP. Berteloot
First select the target : better First select the target : better choice of adjuvant treatments for choice of adjuvant treatments for
breast cancer patientsbreast cancer patientsSt Gallen 2005St Gallen 2005
1 Target = endocrine sensivity1 Target = endocrine sensivity
(low – intermediate -high)(low – intermediate -high)
2 defining the riskgroups2 defining the riskgroups
(low – intermediate- high)(low – intermediate- high)
Break-throughs since 2005Break-throughs since 2005
Herceptin!Herceptin!
Confirmation A.I.Confirmation A.I.
Lower threshold for TaxanesLower threshold for Taxanes
Present ProblemsPresent Problems
Past trials : large but not selectivePast trials : large but not selective
General conclusionsGeneral conclusions
Possibly not suitable for all subgroupsPossibly not suitable for all subgroups
Not pre-planned subgroup analysis are Not pre-planned subgroup analysis are statistically not reliablestatistically not reliable
Need forNeed for Inclusion criteria for future trials should Inclusion criteria for future trials should
be selective for important targetsbe selective for important targets Individualised therapy should be based on Individualised therapy should be based on
reliable and selective tumor informationreliable and selective tumor information Pitfalls of diagnostic proceduresPitfalls of diagnostic procedures
DCIS ~ micro-invasionDCIS ~ micro-invasion Passive transportation of malignant cells -> Passive transportation of malignant cells ->
axillaaxilla Error rate in HR assessementError rate in HR assessement
Depending on different kitsDepending on different kits FixationFixation
Eroor rate in HEREroor rate in HER22 status status Viale G.Viale G.
Importance of local control by Importance of local control by surgery and Radiotherapysurgery and Radiotherapy
Improved local control at 5 years of Improved local control at 5 years of follow-upfollow-up
Proportional survival benefit at 15 Proportional survival benefit at 15 years of follow-up years of follow-up
Ratio 4:1Ratio 4:1
Important highlights of St Important highlights of St Gallen 2007Gallen 2007
MRI staging in breastcancerMRI staging in breastcancer Ipsilateral Ipsilateral : 15-20 %: 15-20 %
Contralateral Contralateral : 3-5 %: 3-5 %
Independent of :Independent of : AgeAge PathologyPathology Mammographic densityMammographic density
C. Kuhl NEJMC. Kuhl NEJM
Breast surgery in advanced Breast surgery in advanced breast cancerbreast cancer
Regained importance due to :Regained importance due to :
Better and longer control of distant diseaseBetter and longer control of distant disease
Ability of detecting small metastatic fociAbility of detecting small metastatic foci
Large retrospective reviews of patients Large retrospective reviews of patients treated by surgical resection of the treated by surgical resection of the
primary tumor to clear borders have primary tumor to clear borders have demonstrated longer survivaldemonstrated longer survival
Predictive factors for Predictive factors for chemosensitivitychemosensitivity
TOPO IITOPO II Sensitivity for anthracyclinesSensitivity for anthracyclines Gene level Gene level ~~ protein level protein level
if proliferation index ( KI67) is elevatedif proliferation index ( KI67) is elevated TaxanesTaxanes
Tau-proteinTau-protein HERHER22 pos ? pos ? P-53 mutationsP-53 mutations
Predictive factors for Predictive factors for chemosensitivitychemosensitivity
AlkylantiaAlkylantia
PlatinumPlatinum
ER positiveER positive
< 35 years< 35 years
HERHER22 signaling signaling
worse prognosisworse prognosis
DNA Damaging Agents in BRCA1 patientsDNA Damaging Agents in BRCA1 patients
Association HERAssociation HER22 – ER- – ER-pospos
Chances of finding HERChances of finding HER22 positivity positivity associated with ER-positivity is associated with ER-positivity is higher in young than in older womenhigher in young than in older women
HerceptinHerceptin
Update Hera-trialUpdate Hera-trial 2 years of follow-up2 years of follow-up 1 year of Herceptin1 year of Herceptin
DFS : 6,3 % DFS : 6,3 % OS : 2,7 % OS : 2,7 %
Compairable gain for all subgroups Compairable gain for all subgroups
2 important questions2 important questions Sequencing ?Sequencing ? Duration of therapy ?Duration of therapy ?
absolute gainabsolute gain
Consensus issues Consensus issues concerning Herceptinconcerning Herceptin
Chemo in HerChemo in Her22 positive patients positive patients
Dependent on receptor statusDependent on receptor status : 60 % yes: 60 % yes
Anthracyclines to allAnthracyclines to all : 73 % : 73 % yesyes
Taxanes to allTaxanes to all : 43 % yes: 43 % yes
6 to 8 cycles6 to 8 cycles : 63 % yes: 63 % yes
Chemotherapy schedules in Chemotherapy schedules in HERHER22 + +
CAF CAF ~ CEF~ CEF : 62 % yes: 62 % yes
AC-TAC-T : 32 % yes: 32 % yes
FECFEC : 32 % yes: 32 % yes
TACTAC : 30 % yes: 30 % yes
FEC-TAXFEC-TAX : 32 % yes: 32 % yes
TAX + carboTAX + carbo : 51 % yes: 51 % yes
The opinions are very devidedThe opinions are very devided
Sequencing Herceptin-Sequencing Herceptin-ChemotherapyChemotherapy
Sequential Sequential : 38 %: 38 %
ConcommittantConcommittant : 40 %: 40 %
No preferenceNo preference : 22 %: 22 %
Duration of Herceptin Duration of Herceptin administrationadministration
Shorter in elderlyShorter in elderly : 51 % yes: 51 % yes Shorter for node negShorter for node neg : 38 % yes: 38 % yes Is duration riskdependentIs duration riskdependent : 40 % yes: 40 % yes Importance of early onsetImportance of early onset : 60 % yes: 60 % yes 12 months12 months : 91 % yes: 91 % yes 9 weeks + Docetaxel9 weeks + Docetaxel : 14 % yes: 14 % yes 2 years2 years : ?: ?
Herceptin indicationsHerceptin indications IHC +++IHC +++ : 92 %: 92 %
FISH requestedFISH requested : 15 % yes: 15 % yes
T<1 cmT<1 cm
Node negNode neg : 56 % yes: 56 % yes
Receptor negReceptor neg
Tx node negTx node neg : 58 % yes: 58 % yes
Receptor posReceptor pos
independent of node and receptorstatusindependent of node and receptorstatus
Safety of HerceptinSafety of Herceptin
Avoid low LVEF (Avoid low LVEF ( 50-55) 50-55) : 74 % : 74 % yesyes
> 70 years> 70 years : 30 % yes: 30 % yes
Preventive use of ace inhibitorsPreventive use of ace inhibitors: 7 % yes : 7 % yes
Hormonal therapyHormonal therapy
Postmenopausal consensus topicsPostmenopausal consensus topics
Tam aloneTam alone Node negNode neg : 50 %: 50 % Node posNode pos : /: / High ER-PRHigh ER-PR : 54 %: 54 % HERHER22 neg neg : 52 %: 52 %
Hormonal therapyHormonal therapy
Postmenopausal consensus topicsPostmenopausal consensus topics
AI upfrontAI upfront In all patientsIn all patients : 19 % yes: 19 % yes High riskHigh risk : 65 % yes: 65 % yes HERHER22 pos pos : 66 % yes: 66 % yes
HERHER22 neg neg : 33 % yes: 33 % yes
Hormonal therapyHormonal therapy
Postmenopausal consensus topicsPostmenopausal consensus topics
If started with TAMIf started with TAMSwitch Switch
allall : 50 % yes: 50 % yes
After 2 to 3 yearsAfter 2 to 3 years : 89 % yes: 89 % yes
After 5 yearsAfter 5 years : 60 % yes: 60 % yes
Only for TAM-intoleranceOnly for TAM-intolerance : 65 % : 65 % yesyes
PreferencePreference
1.1. AI upfrontAI upfront : 31 %: 31 %
2.2. TAM TAM AI AI : 63 %: 63 %
3.3. TAM x 5 TAM x 5 : 5,7 : 5,7 %%
After 5 years of TAM After 5 years of TAM AIAI
AllAll : 84 % yes: 84 % yes
Node posNode pos : 92 % yes: 92 % yes
HERHER22 neg neg : 40 % yes: 40 % yes
HERHER22 pos pos : 74 % yes: 74 % yes
Total duration of hormonal Total duration of hormonal therapytherapy
5 years5 years : 58 %: 58 %
5 to 10 years5 to 10 years : 75 %: 75 %
> 10 years > 10 years : ?: ?
Life-time for high-risk patientsLife-time for high-risk patients :37 %:37 %
Evaluation ovarian function Evaluation ovarian function at the start of AIat the start of AI
By onsetBy onset : 55 % yes: 55 % yes
After 6 to 12 weeksAfter 6 to 12 weeks : 48 % yes: 48 % yes
Supportive care + AISupportive care + AI
Ca + Vit DCa + Vit D : 61 % yes: 61 % yes
Bifosfanates for allBifosfanates for all : 3 %: 3 %
Fysical exerciseFysical exercise : 100 %: 100 %
BMCBMC : 88 %: 88 %
Pre-menopausal : Pre-menopausal : consensus topicsconsensus topics
TAM alone is an optionTAM alone is an option : 92 % yes: 92 % yes
OFS + TAM is an optionOFS + TAM is an option : 83 % yes: 83 % yes
OFS aloneOFS alone For everyoneFor everyone : 7 % yes: 7 % yes
For low riskFor low risk : 32 % yes: 32 % yes
Modality of ovarian Modality of ovarian suppressionsuppression
LHRH analogueLHRH analogue : 100 %: 100 %
SurgerySurgery : 76 %: 76 %
RadiotherapyRadiotherapy : 19 %: 19 %
Depending on age andDepending on age and : 75 % : 75 % histological subtype histological subtype
Duration of ovarian Duration of ovarian suppressionsuppression
2 years for all2 years for all : 29 %: 29 % 2 years node negative 2 years node negative : 43 %: 43 % node positivenode positive 5 years node positive 5 years node positive : 66 %: 66 %
HERHER22 positive positive 5 years for all5 years for all : 25 %: 25 % IndividualisationIndividualisation : 79 %: 79 %
Chemo + OFSChemo + OFS
ConcurrentlyConcurrently : 30 %: 30 %
SequentiallySequentially : 82 %: 82 %
Concurrently to preserve Concurrently to preserve : 65 % : 65 %
fertilityfertility
OFS + AIOFS + AI
AllAll : 6 %: 6 %
Contra-indication for TamContra-indication for Tam : 68 %: 68 %
TrialsTrials : 54 %: 54 %
AI : timing AI : timing attempt to conclusionsattempt to conclusions
Upfront : patients with high risk for early Upfront : patients with high risk for early relapserelapse
High tumorload : High tumorload : T2 ; T2 ; N2 N2
Biological agressivenessBiological agressiveness gr IIIgr III HERHER22 pos pos vascular invasionvascular invasion Negative hormone receptor statusNegative hormone receptor status
Mauriac, Ann OncolMauriac, Ann Oncol
AI : timingAI : timing
Switch after 2-3 years : intermediate Switch after 2-3 years : intermediate riskrisk
Adjuvant hormonal therapy ≥ 5 yearsAdjuvant hormonal therapy ≥ 5 years
Relapse curve receptor positive patientsRelapse curve receptor positive patients
Increased benefit ~ duration extended Increased benefit ~ duration extended adjuvant therapyadjuvant therapy
Saphner et al. J Clin Oncol. 1996;14:2738.
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Years
ER– (n=1305)
ER+ (n=2257)
Long-Term Risk of Breast Long-Term Risk of Breast Cancer Recurrence Cancer Recurrence
Remains High in ER+ Remains High in ER+ PatientsPatients
Annual Risk of Annual Risk of Recurrence by Nodal Recurrence by Nodal
StatusStatus
The risk of late recurrence remains substantial even The risk of late recurrence remains substantial even in patientsin patientswith node-negative tumorswith node-negative tumors
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Saphner et al. J Clin Oncol. 1996;14:2738.
Years
Benefit of TAM +/- OSBenefit of TAM +/- OS
No clear evidence found !No clear evidence found !N. DavidsonN. Davidson
No large prospective randomised trials No large prospective randomised trials availableavailable Actual SOFT trial and TEXT trialActual SOFT trial and TEXT trial
Meta-analysis by Jack CuzickMeta-analysis by Jack Cuzick Limited benefit likelyLimited benefit likely Age dependent ?Age dependent ?
ChemotherapyChemotherapy
Hormone sensitivityHormone sensitivity
indicateindicate : 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
HERHER22 Status Status
Incorporation of taxanesIncorporation of taxanes
Only trials in node pos patientsOnly trials in node pos patients3 – 7 % gain3 – 7 % gain
Level 1 evidence ?Level 1 evidence ? Only PACS 01 has an optimal control armOnly PACS 01 has an optimal control arm PACS 01: imbalance of ER status and PACS 01: imbalance of ER status and
unexplained age differenceunexplained age difference Dependent on:Dependent on:
Hormone receptor statusHormone receptor status HERHER22 positivity ? positivity ?
Conclusion St. Gallen Conclusion St. Gallen 20072007
No consensus yetNo consensus yet
We don’t expect large changes in We don’t expect large changes in our home strategyour home strategy
Guidelines: UZ leuven Guidelines: UZ leuven Adjuvant therapyAdjuvant therapy??