Presentation on theme: "Neoadjuvant Chemotherapy in Breast Cancer"— Presentation transcript:
1 Neoadjuvant Chemotherapy in Breast Cancer Pr Hamouda Boussen MDDepartment of medical oncologyInstitut Salah Azaiz. TunisPost-graduate course of Mediterranean Task Force for Cancer Control and Mediterranean School of Oncology.Hotel El Mechtel. November 14th, Tunis.
3 Neoadjuvant chemotherapy(NACT) OR Primary Systemic Therapy (PST) ?? i.e post-diagnosis systemic therapyTakes into account order of administration, programmation of subsequent treatment and efficacy of systemic interventionOther terms used are down staging, induction therapy, preoperative systemic therapy, neoadjuvant chemotherapy.Kaufmann JCO International Expert Panel
4 Why Pre-operative Chemotherapy? Downstage:Increase operabilityFacilitate breast conservationEarlier treatment of micrometastasesAssess chemotherapy sensitivity
5 PST For whom it is standard of care? For patients with inoperable breast cancerInflammatory breast cancerinvolvement of ipsilateral supra or infraclavicular nodes i.e. N3 disease.What about stages IIIA-B or T3-4 disease ?
6 Locally advanced breast cancer In Tunisia it forms 30 to 40 % of all breast cancers at some centers*.*Cancer registries(North, Center and South)
7 For whom can PST be recommended as an alternative to AST ? Most large randomized trials of PST versus AST indicate that these therapies offer equivalent disease free and overall survival benefits.For operable breast cancer, PST can be considered as an alternative to ASTFor patients appropriate candidates for mastectomy but who desire less extensive surgery (breast conservation surgery).Success rate 5-36 %.Also in patients who can technically have a lumpectomy first but whose physical appearance will be less damaged if PST is given first.
8 PSTMay also be advisable in patients who have medical contraindications to surgery or if they simply wish to delay surgery i.e. pregnant patient diagnosed in second and third trimester.PST offers an optimal test situation for evaluation of new compounds and detection of new biologic or molecular discriminants of either response or resistancepCR may be used as a surrogate for survival, lesscumbersome than overall survival and less time consuming.
9 NSABP B-18 STRATIFICATION • AGE • CLINICAL TUMOR SIZE OPERABLE BREAST CANCERSTRATIFICATION• AGE• CLINICAL TUMOR SIZE• CLINICAL NODAL STATUSOPERATIONAC x 4+ TAM if >50 yrs.AC x 4+ TAM if >50 yrs.OPERATION
10 B-18 Pathologic Breast Tumor Response in pts with cCR (249 pts) CompletePathologicResponse(63 pts)9%36%4%DCIS only(26 pts)ClinicalCompleteResponse(249 pts)23%ResidualInvasive
11 40 32 32 60 68 P < 0.01 68 B-18 Surgery Performed 100 80 Mast 60 Lump60%406068P < 0.012068PostopChemoPreopChemo
12 Era of pre-taxanes : NSABP B-18 trial Overall survival and response to chemotherapy 5yr survivalPath CR = 87%Clin PR = 68%Clin NR = 64%p<0.0001Fisher et al, J Clin Oncol 1988; 16:
13 NSABP B-18: updated results. In pre-op arm 36 % patients had a complete clinical responseAxillary node down staging in preop. patients 59% vs. 42 %path negative nodesHighly significant correlation between tumor responseand path nodal status.87 % patients with complete clinical response hadpath neg nodesMore likely to have lumpectomy 68% vs. 59 %,statistically not differentNo difference in disease free and overall survival
14 Author Local Distant Breast And No.of Follow-up Failure Failure Survival ConservationGroup Patient Stage (months) Rate Rate Rate (PST vs. AST)Fisher, NASBP , T1-3, N0-1, M * * * % versus 60% P=0.002Gianni, ECTO T1-3, N0-1, M NA NA NA % versus 35% P <Van der Hage, T1c-4d, N0-1, M * * * % versus 21% Eortc NAJakesz, ABCSG T1-3, N0-2, M NA ‡ * * *NAScholl, S T2-3, N0-2, M * * * % versus 77%Overview of Randomized Trials of NACT vs ACT(adjuvant chemotherapy) in Breast Cancer*No Statistical difference
15 B-18 trial: unanswered questions. Is there a need for further chemotherapy after surgery ???Those who show a good response may notrequire further treatment and those who showa poor response may require different drugs ???
16 Whether favorable prognosis warrants exposure to known toxicity of treatment B 20 showed that adding adjuvant chemotherapy in node negative women improved disease free survival significantlyNSABP B20 trial removes possible concerns about preoperative chemotherapy in patients with favorable tumor size, receptor status and histology.General consensus: that there is no group that is not benefited by chemotherapy: very small palpable tumors, node positive and negative, ER positive and negative, all benefit.
17 PST: Which regimen and how much Anthracycline based chemo was standard, but changing fastA minimum of 3-4 cycles, additional cycles may be considered for responding patients to maximize response and to improve chances of breast conservationUse of Taxanes and sequential therapies can increase rate of pCR / successful breast conservation surgery / node negative patients by 50%.Trastuzumab and other targeted therapies are under investigation.
18 Role of Docetaxel in neo-adjuvant therapy for breast cancer
19 Rationale for the use of Docetaxel in PST Activity in anthracycline-resistant MBCSuperior activity observed in patients with poor prognosis diseaseMost effective drug in first-line MBC (single, combined)No cardio toxicity as with paclitaxelMore lab & clinical activity in breast cancer than paclitaxelLonger half life than paclitaxel
20 Important questions for Docetaxel Does the addition of Docetaxel to an anthracycline- containing regimen have beneficial effects?Clinical and pathological responsesBreast conservationSurvivalShould Docetaxel be given concurrently with or following an anthracycline-containing regimen and what is the best schedule?What about role of trastuzumab in HER2 over- expressing tumors?
21 Neoadjuvant Taxotere The Aberdeen Trial NSABP B27 GEPARDUO
22 Neoadjuvant Taxotere The Aberdeen Trial NSABP B27 GEPAR-DUO
23 Tax301 Study Conducted by the Aberdeen Breast Group First PhaseSecond phase4 cycles of TaxotereAll PatientsNo Response4 cycles of CVAPFinal Assessment / SurgeryResponse4 cycles of TaxotereRandomise4 cycles of CVAPSmith et al, JCO 2002
24 Aberdeen Tax 301 Objective clinical response rates 1st phase: 4 cycles CVAP ORR - 67%N=162 patients; 4 cycles of CVAP given to all patients
29 Neoadjuvant Taxotere The Aberdeen Trial NSABP B27 GEPAR-DUO
30 Operable Breast Cancer NSABP B-27( 2411 pts )Operable Breast CancerRandomizationAC x 4Tam X 5 YrsAC x 4Tam X 5 YrsAC x 4Tam X 5 YrsSurgeryTaxotere x 4SurgerySurgeryTaxotere x 4Bear et al, J Clin Oncol 2003; 21
31 B-27 Eligibility Operable Breast Carcinoma Diagnosis by FNA or core biopsyPalpable on physical exam (T1c-3 N 0, M 0 , / T 1-3, N 1, M 0 ).NOT locally or regionally advancedNo T4 or N2 diseaseBear et al. Breast Cancer Res Treat. 2004;88(suppl 1):S16. Abstract 26.22
33 Pathological Response (pCR) in Breast NSABP B-27Pathological Response (pCR) in BreastNo TumourNon-Invasive30p < 0.0012018.9%26.1%109.8%13.7%7.2%3.9%ACN=1567AC TaxotereN=786Adapted from Bear et al, J Clin Oncol 2003; 21
34 NSABP B-27: Proportion of Patients with negative axillary lymph nodes 8060%58.24050.8p < 0.00120ACN=1534AC TaxotereN=752Bear et al, J Clin Oncol 2003; 21
35 NSABP B-27: Breast Conservation 8060%636140p = 0.7020AC(N=1492)AC TaxotereN=718Bear et al, J Clin Oncol 2003; 21
36 Neoadjuvant Taxotere The Aberdeen Trial NSABP B27 GEPAR-DUO
37 Geparduo GEPARDUO trial AT + Tam AC-T +TAM T 2 cm (stage I,II) Surgery(N=913)T 2 cm(stage I,II)SurgeryAC-T +TAMAdriamycinTaxotereAdriamycinCyclophosphamidevon Minckwitz et al., J Clin Oncol 1999von Minckwitz et al., J Clin Oncol 2001Taxotere
38 Adapted from G.Raab – SABCS ’03, Abs#241, Poster Treatment regimens4 cycles AC followed by 4 cycles of TaxotereDoxorubicin mg/m² (day 1 q 22)Cyclophosphamide 600 mg/m² (day 1 q 22)Taxotere mg/m² (day 1 q 22)4 cycles ATDoxorubicin 50 mg/m² (day 1 q 15)Taxotere 75 mg/m² (day 1 q 15)G-CSF (days 5-10)Tamoxifen 20mg /day at same timeAdapted from G.Raab – SABCS ’03, Abs#241, Poster
39 Clinical responses in the breast 100%32.5%80%57.4%Complete60%Partial44.7%Stasis40%Progress29.4%20%21.1%10.1%0%ATAC-T(n=421)(n=425)
40 P < 0.001 GEPAR-DUO Pathologic Complete Remission (pCR) 16.1% 7.7% No TumorIn situ residuals only30%P < 0.00120%16.1%22.4%10%7.7%11.5%6.3%3.8%AT(443 pts)AC Taxotere(442 pts)Adapted from G.Raab – SABCS ’03, Abs#241, Poster
41 Effect on tumour in axillary lymph nodes 80%60%60.7%55.4%40%20%AT(n=443)AC Taxotere(n=442)
42 Effect on breast conservation surgery GEPAR-DUOEffect on breast conservation surgery80%74.9%60%65.5%40%20%AT(n=443)AC Taxotere(n=442)
43 GEPAR-DUO : Conclusions AC->Taxotere :Increased Complete Clinical responseIncreased pCR ratesIncreased number of patients with no axillary node involvementIncreased breast conservation
44 Author Clinical Pathologic Breast And No.of Complete Response* ConservationGroup Patient Stage Regimen Response(%) (%) RateNSABP 2,411 T1-3, N0-1, M0 AC xAC x 4, Doc xVon Minckwitz 913 T2-3, N0-2, M0 AT x 4 q2wGABG AC x 4, Doc xUntch, AGO † T2-4d, N0-2, M0 ET x NAEpi x 3, Tax x 3 q2wVon minckwitz 248 T2-3, N0-2 AT x 4 q2wGABG AT x 4 q2w + TamPenault-Llorca ‡ NA AC NAFrance ATBuzdar T1-3, N0-1, M0 FAC xHouston Tax xSmith T2-4, N0-2, M0 CVAP x §CVAP x 4, Tax x §Overview of Rand. Trial comparing different Primary Systemic Therapy Regimens in Breast Cancer*No invasive or in situ tumor cells in the removed breast
45 Population Size* All Randomized Trials Number of studies meeting criteria:Number of patients enrolled in non-TAX: 1443Number of patients enrolled in TAX:Overall Number of patients: *All Randomized Trials* Updated after abstract submission
46 Pathological Complete Response Rate (pCR) Method B
47 Randomized controlled trial of TX vs Randomized controlled trial of TX vs. AC as primary therapy in early breast cancerLee et al ESMO 2004RandomizationAC x 4TX x 4PrimarySurgerySurgeryRandomized controlled trial of TX vs. AC as primary (neoadjuvant) therapy in early stage breast cancer. Aims of the study were to evaluate clinical and pathologic responses and compare safety of TX vs. AC.Treatment doses:AC = doxorubicin (60mg/m2 i.v. day 1) + cyclophosphamide (600mg/m2 i.v. day 1).TX = docetaxel (75mg/m2, 1-hour infusion on day 1) + capecitabine (1000mg/m2 twice daily, days 1-14).If no response was obtained prior to surgery, patients crossed over to the other regimen before undergoing surgery.Patient evaluation:Baseline physical exam, PET (to exclude node-negative disease) and ultrasound (to determine tumor size) prior to first cycle of chemotherapy.Repeat ultrasound of affected breast prior to the third cycle of chemotherapy and surgery.Repeat CT or PET performed prior to surgery if indicated.Patients underwent mastectomy or lumpectomy after fourth cycle of primary chemotherapy; patients then crossed over to other treatment arm.For unresponsive tumors (SD or PD), surgery or alternative chemotherapy offered at physicians’ discretion.Patients received radiotherapy tamoxifen following chemotherapy.Statistical analysis:209 evaluable patients required to detect 15% difference in pCR rate with 80% power at 5% significance level, (allowing for up to 10% withdrawal rate.).Patients prospectively stratified according to disease status (stage II or III), estrogen receptor status (positive or negative), and age (50 years vs. >50 years).TX x 4AC x 4Adjuvant
48 Taxotere in ESBC: Conclusions Addition of Taxotere to conventional anthracycline-containing chemo DFS and OS in N+ early-stage breast cancerSequential use of Taxotere following 3 cycles of an anthracycline-containing regimenNeoadjuvant chemo can increase operability in operable and locally advanced breast cancerClinical and pathologic response predict outcomeTaxotere-containing regimens for ESBC are safe and provide significant clinical benefitTaxotere-containing combinations and sequences are a valid treatment option for women with early-stage breast cancer
49 MD Anderson Neo-Adjuvant Herceptin Trial Operable Breast Cancer - Her-2 +Paclitaxel X 4FEC X 4Paclitaxel X 4 + H X 12 wklyFEC X 4 + H X 12 wklyLocal TherapyRandomizationAppropriate Endocrine Therapy for Patients with Hormone Receptor + Disease
50 Summary neoadjuvant Taxotere Taxotere offers meaningful benefits to patients:Highly effective in reducing tumour sizeIncreases clinical responsesIncreases complete pathological responseIncreases Nodal clearanceIncreases breast conservationImproved survival in Aberdeen trialPotential for non-anthracycline combinations
51 Primary Systemic Chemotherapy It is here to stayEffective, improved results in combinationIncreased rates of breast conservationBetter cosmesisSurrogate marker of improved survivalRescue measures can be taken early rather than late
52 PST; Drawbacks Pathological staging not available Improved survival not provenWhether post operative chemotherapy is beneficial not knownCan create problems in RadiotherapyNewer options: AI, Trastuzumab
53 Adjuvant vs neoadjuvant chemotherapy in breast cancer: randomised studies StudyNo. ptsStageDFS(%)OS (%)Ragaz, 1999204I,IINR73 vs 72Mauriac, 199969T2,T3same54 vs 55Semiglazov,1994271IIb,IIIa81 vs 72*86 vs 78Scholl, 1994414IIa - IIIa59 vs 5586 vs 78*cCR=clinical complete remission in %, pCR=pathological complete remission in %,BST=breast conserving treatmentS=surgery,FECi=5-FU, epirubicin, cisplatinVbEM=vinorelbine,epirubicin,methotrexateFMxC=5-FU, mitoxantrone, cyclophosphamideTAVbCF*=doxorubicin, vinorelbine, cyclosphamide, 5-FU w/wout colony stimulating factorCMF=cyclophosphamide, theotrexate, 5-FUFAC=5-FU, doxorubicin, cyclophosphamideFEC=5-FU, epirubicin, cyclophsphamideA=doxorubicinMakris, 1998309T0 - T484 vs 82sameFisher, 19981523T1 - T367 vs 6780 vs 80(Data from: Wolf and Davidson, J Clin Oncol 2000; *p<0.05)
54 PST: Endocrine therapy remains attractive When it is desirable to avoid chemotherapyAs a second choice for selected patients, elderly women with impaired organ function or low PS, or high surgical riskA positive ER, PgR is a requisite.AI more active and better tolerated, thus preferred in postmenopausal patients.No data in premenopausal patients.
55 Locally advanced breast cancer Increased public awareness, national breast screening10-20% of patients - LABC (T3, T4 or N2)Haagensen & Stout, 194348% local recurrence3% 5 year survival}If radical mastectomyperformed
56 Alternative treatment strategies for LABC RadiotherapyChemotherapyChemoradiotherapyClinical responses of 60-70% with various chemotherapies
58 Pathological Response and Survival (Miller and Payne grading system) 51.00.90.80.126.96.36.1993survival2p=0.003*1monthsOgston et al, 2003
59 Pathological responses Miller & Payne Grade of Pathological Response Aberdeen Tax301Pathological responsesMiller & Payne Grade of Pathological ResponseCVAPn = 52Taxoteren = 52119%2%pNR219%17%327%23%415%17%pCR515%31%**p=0.06Hutcheon et al, SABCS 2003
60 NSABP B18: Updated results Still no difference in overall survivalPathological complete response - 85% year survival at 9 yearsAgeDFINeoadj vs adjOSNeoadj vs adj49 and under55% vs 46%71% vs 65%50 and over56% vs 60%67% vs 75%Wolmark et al, 2001
61 NSABP B-27 trial All patients receive initial AC chemo Group I; No further treatmentGroup II: 4 cycles of Docetaxel after surgeryGroup III: 4 cycles of Docetaxel before surgery
62 NSABP-B27 Clinical complete response rates 36-40% vs 65 % Path CR 9 % and 18 %
63 PST:Is there a role for endocrine treatment alone Conventionally response rates with endocrine therapy are far inferiorIn a largest trial so far of 337 patients, a pCR was observed in only 1.5 % patients. Eiermann et al. Ann Oncol 2001.But things may be changing soon, Aromatase inhibitors have shown better responses in small studies.
64 2nd phase: non-responding patients Aberdeen Tax3012nd phase: non-responding patientsMiller & Payne Gradeof PathologicalResponseTaxoteren = 46115pNR21131346pCR5120 (44%) patients had a grade 3,4 or 5 response
65 Taxotere and paclitaxel Similar mechanisms of action, but some differencesTaxotere has:Greater affinity for tubulinLonger half-lifeLonger intracellular retentionLower cardio toxicity with doxorubicin
66 PST: scientific basisPulmonary metastases in animals underwent growth spurt on removal of primary tumor, this can be overcome by prior chemotherapyGrowth fractions in cell populations suggest micro metastases might respond differently to preoperative chemotherapyGoldie–Coldman hypothesis suggests that resistance to chemotherapy was a function of time, hence early treatment might be better.
67 TAX 301 Study After 4 cycles of CVAP and Taxotere: Increased the complete response rate to 62% in initially responsive patients vs. 34% for continued CVAPpCR of 31% (ITT analysis)increased 5 year DFS and SurvivalAchieve a higher rate of Breast conservation
68 TAX 301 StudyPatients unresponsive to primary CVAP chemotherapy receiving further sequential Taxotere achieve :47% Clinical ORR1 Complete pathological response
69 NSABP B-27 : ConclusionsThe addition of preoperative Taxotere to preoperative AC resulted in a significant increase in the rates of:Clinical Complete Response: 40% vs 65% (63% )Pathologic Complete Response: 13.7% vs 26.1% (91% )Negative Axillary Nodes: 50.8% vs 58.2% (16% )
70 PST; Early rand. trial Scholl et al from Institut Curie 414 premenopausal women, T2,T3,N0-N14 cycles CAF followed by RT (surgery only for those who did not have CR) VS Surgery followed by 4 cycles of same chemoFU 54 months OS better in primary chemo arm, no difference in disease free survival or local recurrence
71 Bordeaux trial272 women with lesions more than 3 cms rand between mastectomy and chemo if nodes positive VS initial chemotherapy followed by RT/ surgery34 months FU patients with initial chemo better overall survival, however more isolated recurrence occurred in these patients.
72 Clinical response rates in neoadjuvant Taxotere studies concurrentsequentialsingle agent79% (B18)29% of tumours < 2cm in the B18 study
73 Neoadjuvant therapy Initial concept Evolution of concept Early Introduction of chemotherapyUnic Clinical situation clinique permitting to analyse tumor response in vivo Benefit on survival Increase of breast conservation rate Reduction of loco-regional sequelaeAnalysis of response in vivo may be done in sequential (repeated samples)Identification of intermediate markers (« surrogate markers »)Méta analyse neoadjuvant CT vs adjuvant CT, JNCI 97,3, 2005Identification of factors predicting response No difference in term of overall and disease-free survival Higher rate of breast conservation MorphologicalImmuno-phenotyping Genomics
75 Dose-dense Phase III AGO trial : results et 55 months B: Epi 90 + Taxol 175q3w x4A: Epi 150 q2w x3Taxol 250 q2w x 3Surgery3CMF adjuvantpRC10%19%I’pN-41%50%DFS 368%76%P<0.05DFS 559%70%B’OS 385%90%OS 577%83%Untch M. et al, SABCS 2007, abstract 5052
76 + Herceptin Q3W if HER2 +, follow-up 1 year post surgery GeparQuattro trial- Phase 3 GBG/AGOEvery patient eligible for an adjuvant chemotherapy4 EC904 D 1004 D75 +X18004 D754 X 1800+ Herceptin Q3W if HER2 +, follow-up 1 year post surgery4 D 1004 D75 +X18004 D754 X 1800TotalHER2+147144136427HER2-324327343994I’No difference in term of cardiac toxicity betw HER2+ and –, More febrile neutropenia in HER2 +A’Untch M. et al, SABCS 2007, abstract 5053* Von Minckwitz G. et al, SABCS 2007, abstract 79
77 TPN = unic factor prédictive of CR Phases II – Neoadjuvant ChemotherapyProtocolSchemeNb PtsResultscommentRoché5057RCEX (vs FEC)X 1800E100C500182RR 58%pCR 13% CEX, 20% FECsafetyLombardi Aviano5067DE q3 w x 4D 75E 9045(23 HER)pRC 20%pRC axil 25%pRC breast +node ?Le TourneauCurie R4010FAC q3wTRIPLE NEGET HER2+F 700 J1 J5A 60C 700 J1 J896pCR 20%TPN : 47% pCRHER % pRCTPN = unic factor prédictive of CRAlkylants+++ShenChine5070DxrL + V q3w x6Caelyx 30V 25 , J1 J861pRC 3.4%Tox muqueuse ++And hématoAlvarezBarcelone5068Doxo lipos. +DQ2w x 6M 60D 6058pRC 19.2%ABSTRACT 5073 DE CITY OF HOPE39 PTES P2 RANDOM REPONSES AFFICHEES NON PRECISEES SI CLINIQUE OU PATHOIII’
78 Phase II - Her2+ Protocol Scheme Nb Pts Results comment III’ Tripathy Roche5059DXHD 75X 1650H hebdo34pRC + quite 52% of pCRHanMiami5060DCH q2wCarbo 6D 7032pRC 40%Better for the 14dys schemePernas Barcelone5061P hebdo puis 4 FEC75P 80 H x124 FEC 75H hebdo 24w33pRC 73%Ki 67> 20 : pRC81% vs 43% si <20GEICAM5069Dxr L + D q3w x6Myocet 50D 60H226pRC 30.8%MD Anderson5054FEC + Herthen Txt X Hebdo179pRC 34%pRC 43% Triple negSignature prédictive pf pRC?CreightonHouston 82Lap 6w puis TH q3w x4Lap 6w then TH q3w x42560% after lappRC total 63% of CD44+ CD24- after lap. (10.6 à 4.7%)III’
79 Phase II – Targeted therapies 100% de l’act. Enzymatique FTase ProtocolSchemeNb PtsResultscommentMakhoul50554TCB 4Aq3wD75CPM 500Avastin 15Dxr 6028pRC 29.3%1 death ?1 CaFail clinicalGreil4064TXB q3wX 190018pRC 22%EjlertsenREC +/- Iressa 250144RH-pRC 11%Iressa = placeboSparano5071AC +Tipifarnib46pRC sein 26%pRC tout 20%100% de l’act. Enzymatique FTaseIII’
80 Neoadjuvant chemotherapy and lobular carcinoma Retrospective study 32 patientsFew down staging pCR 2/4 if HER2 with Herceptin* Sinon : 0%Conclusion No neoadjuvant chemotherapy for lobular carcinoma ?Non gradableVrancken Peeters M-JTFD et al, SABCS 2007, abstract 5074
81 Predictive factors Analysis of responses according to subtypes 48 77 156 pts. Anthracycline taxane herceptin (if HER2+ )BasalNon basalHER2 3+RH+/ HER2 négN48773245pRC%23193111No diff between basal and non basalSignific Diff between HER2 + and RH+/HER2-Allada N. et al, SABCS 2007, abstract 5076
82 Predictive factors of pRC Question : Does pCR is related to level of hormone receptors ?185 ptsHR+Neoadjuvant CT 6 FEC 100Biopsy before chemotherapyRETotalSc 3-5Sc 6-7Sc 8-9pRC (%)73292PgR rate didn’t predict responsePetit T. et al, SABCS 2007, abstract 4024
83 Predictive factors : Remagus 170 pts4 EC 75 q3w then 4 D 100 q3wHER2 -HER2 +NoIaCelecoxibIbNoIIaTrastuzumab initialIIbpRC G188.8.131.526.711%G21.03.86.913.35.5%RE+RE-RP+RP-HER2+without THER2-with TTPNpRC%2.4311.722.113.812.73036p<0.0001<0.0006NSMarty M. et al, SABCS 2007, abstract 5058
84 Sentinel node biopsy after NACT PosterMethodResultsNP3004ClasseFrance GANEA195 patientes, cancers stade II et III, traitées par CNA, GS et CA.Taux de détection = 90,2%Faux négatifs = 11,5 %3023BauerfeindAllemagne76 patientes traitées par CNA, GS et CA. Pas toutes repérées au RI et bleu. 3 centresTaux de détection = 95,65%Faux négatifs = 16,6 %III’III’Essai SENTINAN- clinN+ clinGanglion sentinelleGS -GS +Chimiothérapie néoadjuvanteRienCurageG sentCurageN- clinN+ clin
85 Local recurrence after BCT 5-6% in those who achieve CR9.7% in those who do not achieve CRLocal recurrence did not correlate with the sizeof the primary tumor before treatmentPoor response to PST is a predictor of poor prognosis and high risk of recurrenceA demonstrable response may have a positive outcome on the psyche
86 PST; poor response Immediate surgical intervention is indicated? Alternative chemotherapy i.e. non cross resistant agents like Taxanes an obvious choice, about 50 % patients can respond but require close monitoring.Trastuzumab and other new targeted therapies are still under investigation and should not be used outside clinical trialsSmith 2002 JCO.
88 PST: How should the diagnosis be confirmed before PST Core biopsy most appropriateHighest diagnostic accuracy by doingthree biopsies, 14 gauge needle
89 PST: How should be the initial tumor localized ? Risk of poor delimitation of primitive breast lesion in case of objective responseInterest of clip or harpon delimitationPermit a better carcinologic surgery
90 How should tumor location be documented Collaboration of surgical, medical oncologist and radiologistTwo major problems can occur:Either a very quick and complete response so that the primary lesion cant be identifiedOr no response, in that case surgeon may have to intervene.Precise documentation of the tumor on sketch, inserting clips or coils in the center of the lesion or placing a tattooStereo-tactic localization using mammography is another optionComplete pathological CR becoming more common, so it could become a major issue .
91 PST; Should markers be assessed before PST Typing of tumor and assessment of surgical grade impossible because of changes due to chemo, hence preferably to be done on core tissue .Similarly ER/ PR and Her 2 or Ki67 to be done on core tissue before PST.Pathological nodal status is not available reg. prognosis and radiotherapy (a major drawback)However pathological nodal status after PST of relevant prognostic importanceData not clear reg. need for axillary biopsy or sentinel node before chemotherapy.
92 Can breast conservation be increased by PST ? (RCTs of neoadjuvant vs adjuvant chemotherapy)
93 How, when and how often should the effect of PST be monitored Palpation of lump and axillary nodes at the start of each cycleMammography and ultrasound are additional toolsMRI and PET of the breast being studiedDynamic studies(IGR)Importance of morphologic response : Centrifuge, centripete correlation with pCR
95 PST; Surgical treatment of the tumor To obtain clear margins of > 1 mmNo compromise should be made on surgical margins to obtain better cosmetic resultNo difference in PST and AST in 8 year local recurrence ratesPatients less than 40 years and those with larger tumors, high rates of tumor proliferation or close or involved margins are at higher risk of local recurrenceThere is an increased rate of second surgical procedures.
96 Role of Postoperative chemotherapy after PST Till date no data to support or negate the use of chemotherapy after PSTData may become available from NSABP B 27 or fromEuropean Cooperative trial in Operable Breast Cancer
97 PST:When and where should postoperative radiotherapy be administered Same indications as for adjuvant treatmentDecision should be based on pre-PST findings.No definitive data on the importance of nodal status after PST and need for axillary radiotherapyRadiotherapy is not a substitute to surgery, loco-regional control is inadequate when patient is treated with RT alone.
98 Après un FEC100Après 6 FEC100Après un FEC100Après 6 FEC100