Download and Preview : Systemic School Of Medicine LSU Health New Orleans
Report CopyRight/DMCA Form For : Systemic School Of Medicine LSU Health New Orleans
Systemic Therapy for BreastAdjuvant or NeoadjuvantAGUSTIN A GARCIA MD MMMPROFESSOR OF MEDICINE AND SECTION CHIEF HEMATOLOGY ONCOLOGYCHARLES W MCMULLIN III AND RICHARD PAUL GRACE CHAIR IN CANCER RESEARCH.LOUISIANA STATE UNIVERSITYNEW ORLEANS LA DisclosureI have the following relationship s with commercial interests NAME OF COMPANY Celldex Seattle Genetics Iovance.RELATIONSHIP InvestigatorRECEIVED GrantsA commercial interest is any entity producing marketing re selling or distributing health care goods or services consumedby or used on patients . Breast CancerMortality by Race The 20 Century thFrom radical to more breast conserving surgeryRemoval of wholeInoperability criteria No difference in survival.breast includingestablished for locally with radical mastectomypectoral muscles andadvanced breast cancer or lumpectomyaxillary lymph nodes.Modified radicalRadical mastectomy Sentinel lymphmastectomy and node mappingsupraclaviculardissection.Winchester DP et al Surg Oncol Clin N Am 2005 14 479 Advances in the Adjuvant Treatment of Breast CancerCALGB 9741 NSABP B31NSABP B14 Dose dense AC P AC P vs NeoSphereTamoxifen vs Standard dose AC P.AC P Chemo TrastuzumabNSABP B15 trastuzumabIstituto AC vs CMFCALGB 9344 Chemo T .Nazionale pertuzumabNCIC MA 5 BCIRG 001 Milan NCCTG N9831 ExteNETCEF vs CMF TAC vs FACCMF vs AC P vs AC P Chemo T vs.placebo FASG 05 trastuzumab vs Chemo TFEC100 vs NSABP B28 AC P trastuzumab NeratinibFEC50 AC vs ACP1970 1980 1990 2000 Letrozole vstamoxifen BIG 01 01 HERA CREATE X.Local therapy TNBCT AC vstrastuzumab NeoadjuvnantNSABP B05 B07 TACMelphalan vs placebo Chemo Post.EBCTCG BCIRG 006 CapecitabinePACS 01 meta analysis FEC vs Anthracycline trastuzumab vsNSABP B08 B10 FEC T based regimen vs.TCb trastuzumabMelphalan 5 FU CMF Adjuvant Chemotherapy Effects on RFS long term follow up N 386 node positive patients . 35 decrease in risk of recurrence 24 decrease in risk of death P 0 04 Bonadonna et al N Engl J Med 1995 332 901 906 Adjuvant ChemotherapyEffects on RFS.EBCTCG 2000 Lancet 2005 Adjuvant ChemotherapyEffects on OS Multidisciplinary Management of Breast Cancer Surgical Management. Systemic Therapy Endocrine Therapy RadiationHER2 Targeted TxMastectomy.ChemotherapyConservation Neoadjuvant Chemotherapy for Breast CancerHistorical PerspectiveAnhracyclines for.Locally Advanced Locally Advanced NeoadjuvantInoperable Breast Inoperable Breast NeoadjuvantChemotherapy in allCancer Haagensen Cancer Chemotherapy Trials forStages to Allow Breast.all Stage III DiseasePalliative Care Response Rate 72 Conserving SurgeryMastectomy 44 Hortobagyi HortobaGN Cancer.1983 Cancer llat C 1988 Cance Neoadjuvant or PreOperative ChemotherapyA Reduce Distant MetastasisB Select Individualized Therapy for Non Responders.C Improve surgical care Down stage Tumor Allow less extensive surgery Facilitate breast conserving surgery Improve cosmetic outcome. Neoadjuvant or PreOperative ChemotherapyA Reduce Distant Metastasis Long term outcomes for neoadjuvant versus adjuvantchemotherapy in early breast cancer meta analysisEBCTCG Lancet Oncol 2018. Neoadjuvant or PreOperative ChemotherapyA Reduce Distant MetastasisB Select Individualized Therapy for Non RespondersC Improve surgical care Down stage Tumor. Allow less extensive surgery Facilitate breast conserving surgery Improve cosmetic outcome Pathological complete response and long term clinical benefit in breast cancer the.CTNeoBC pooled analysis Cortazar P et al Lancet 2014 Jul 12 384 9938 164 72 Associations between pathological complete response andevent free survival and overall survival Association between pCR and event free survival by.breast cancer subtype Benefits of Monitoring Efficacy to NeoadjuvantChemotherapy GeparTrio TrialEarly Responder.T2 or LN Breast NeoadjuvantTAC Docetaxel Adriamycin CyclophosphamideNX Vinorelbine CapecitabineVon Minckwits G et al J Clin Oncol 2013 GeparTrio Results. Patients with Triple Negative Breast Cancer who do notachieve a pCR have a poor prognosis Post Operative Chemotherapy in Patients with ResidualDisease after Neoadjuvant Therapy CREATE X Trial.CapecitabineStage I IIIHER2 neg Neoadjuvant Surgery No pCRChemotherapyObservation.Masuda N et al N Engl J Med 2017 CREATE X Results CALGB 40603 Addition of Carboplatin toNeoadjuvnat Chemotherapy in Triple Negative BreastWeekly Taxol x 12 ddAC x 4.Weekly Taxol x 12Stage II III Bevacizumab ddAC x 4Negative Weekly Taxol x 12Breast Cancer CarboplatinWeekly Taxol x 12.Carboplatin ddAC x 4Bevacizumab CALGB 40603 Results What we know about the results ofNeoadjuvant Chemotherapy. Achieving a pCR is associated with excellent survival Patients without a pCR or poor clinical response have apoor prognosis Switching chemotherapy in poor responders leds toimprove outcome. The addition of carboplatin improves pCR Proposed Approach to Neoadjvuant Chemotherapy inTriple Negative Breast CancerStandard A Good Response weekly taxol or.Standard surgeryTriple Negative EvaluateAC or TC Breast Cancer Responsex4 Weekly Taxol or.Poor Response A Carboplatin HER2 positive breast cancer Approx 15 of all breast cancers More common in younger women . Tend to be larger more likely to involve LN and be high Poor prognosisKillelea BK et al Am J Surg 2017 Summary of Trastuzumab TrialsNSABP B 31 HERA.52 wks 1 Yr 2 YrPax HD q 3 wk4 cycles No therapyTrastuzumabDox Cyc Standard.4 cycles TrastuzumabPax HD q 3 wk TrastuzumabNCCTG 9831 BCIRG 00612 wks 52 wks 64 wks DocetaxelTrastuzumab.Pax LD wk Dox CycTrastuzumab DocetaxelDox Cyc DocetaxelPax LD wk TrastuzumabCarboplatin.Pax LD wk Trastuzumab Accepted Principles of Neoadjuvant Therapy Affords outcomes identical to adjuvant therapy Improves operability of inoperable locally advanced breast Improves breast conservation rates. Improves outcome in Inflammatory Breast Cancer Standard of Care 10 year results of adjuvant Chemotherapy Trastuzumab37 improvement.in SurvivalPerez E et al J Clin Oncol 2014 Neoadjuvant Chemotherapy for HER2 positive BreastCancer NOAH StudyChemotherapy Alone Surgery.Locally AdvancedHER2 Positive BreastChemotherapy TrastuzumabLocally Advanced.Triple Negative BreastCancer Chemotherapy SurgerytGianni L et al Lancet 2010 NOAH Trial ResultsRates of pCR.HER2 Pos Chemo aloneHER2 Pos Chemo TTriple Negative NEOSPHERE RESULTS ExteNET Results.33 Reductionin Recurrence What we know about the results ofNeoadjuvant Chemotherapy in HER2 PosBreast Cancer. Achieving a pCR is associated with excellent survival Patients without a pCR or poor clinical response have a poor The addition of pertuzumab significantly improves pCR The addition of neratinib after trastuzumab significantly improves Proposed Approach to Neoadjvuant Chemotherapy in.HER2 postivie Breast CancerStandard TreatmentNo neratinibHER2 positiveChemotherapy Surgery.breast cancer Standard TreatmentNo pCR Neratinib afterTrastuzumab Neoadjuvant or PreOperative Chemotherapy.A Reduce Distant MetastasisB Select Individualized Therapy for Non RespondersC Improve surgical care Down stage Tumor Allow less extensive surgery. Facilitate breast conserving surgery Improve cosmetic outcome Effects of Neoadjuvant Chemotherapy onTrial Rate of BCT Surgery First Chemotherapy First.Royal Marsden 78 89Institut Curie 77 82NSABP B18 60 67EORTC 21 37 Challenges with Neoadjuvant Therapy. Effects of surgery in Risk of Local Recurrence after NeoadjvuantChemoterapy Considerations for Lumpectomy after NeoadjuvnatChemotherapy Remove any suspicious clinical or radiologic findings. Generous sample of normal breast tissue It is not necessary to remove the entire volume of tissue initially occupied by If viable tumor is present throughout the specimen even if it does not extendto the margin a further re excision should be considered American College of Radiology American College of Surgeons College of.American Pathology Society of Surgical Oncology Management of the Axilla After NeoadjuvantChemotherapy NAC NAC downstages axilla in up to 40 of patients Consider SLNB after NAC and avoid ALND . Influence of pretreatment clinical node stage SLN Biopsy after Neoadjuvant ChemotherapycN1converted to CN0ACOSOG Z1071 SENTINA SN FNACNumber of patients 649 592 153.Mapping Dual Recommended Technetium required Technetium required Pre op biopsy Yes Not required YesNodal pCR 41 52 35IR 92 7 80 1 87 6False Negative Rate 12 6 14 2 8 4.1 SLN 31 5 24 3 18 22 SLN 21 1 18 5 4 9 3 SLN 9 1 7 3 NS SLNB after Neoadjuvant Chemotherapy Considerations. Use Dual agent mapping Normal Physical Exam and axillary US after chemotherapy Remove 2 nodes Place a clip at time of LN biopsy Include IHC and micromets as node positive. Intraoperative Frozen Section of all nodes ALND required for Failed Mapping 3 nodes Any positive LN. Post NAC Trials of Axillary Management br cN1 to cN0Can axillary RT replace ALNDCan Response to NAC be used to select Radiation Is there a role for neoadjuvant endocrine 21 Gene Recurrence Score. Genomic Profiling to Identify Patients who do notrequire adjuvant chemotherapy Should patients with HR HER2 neg breastcancer receive neoadjuvant chemotherapy Bear HD et al J Surg Oncol 2017. Chart TitleGroup A RS 11 NHT Goup B RS 11 18 NHT Group C RS 11 25 NCT Group D RS 25 NCTResponse pCR Succesful BCSNHT Neoadjuvant Endocrine TherapyNCT Neoadjuvant Chemotherapy. Neoadjuvant Chemotherapy Summary and Future 40 60 of patients with triple negative or HER2 positive breastcancer achieve a pCR with neoadjuvant chemotherapy Patients with pCR have an excellent prognosis independent of.clinical stage or tumor characteristics Do patients with pCR benefit from local therapy surgery and orradiation Can these patients be identified preoperatively Neoadjuvant Chemotherapy .Summary and Future 40 60 of patients with triple negative or HER2 positive breastcancer achieve a pCR with neoadjuvant chemotherapy Patients with pCR have an excellent prognosis independent ofclinical stage or tumor characteristics. Do patients with pCR benefit from local therapy surgery and orradiation Can we avoid surgery in patients with a pCR Can thesepatients be identified preoperatively Neoadjuvant Chemotherapy.What is next Why avoid surgery Morbidity Breast Deformity Acute and Chronic Pain. Hematoma fat necrosis seeroma Anesthesia risk Cost and rationale use of resources Outpatient surgery 12 000 per patient Patient s preference. Can we avoid surgery in patients who achieve a pCR Can we avoid surgery in patients who achieve a pCR Problem pCR identified after surgery Can we avoid surgery in patients who achieve a pCRProblem pCR identified after surgery. Imaging studies in identifying pCRStudy Mammography Ultrasound MRINPV FNR NPV FNR NPV FNR Schottt 91 9 91 9 94 6Peintinger NPV 93 FNR 7 NR NR.Chen NR NR NR NR 74 26Bhattacharyya NR NR NR NR 96 NRKeune 86 NR 85 NR NR NRCroshaw 30 70 33 67 44 56De Los Santos NR NR NR NR 47 NR.Schaefgen 52 13 51 24 60 4Van la Parra R et al Breast Cancer Rest 2016 A Clinical Feasibility Trial for Identification of ExceptionalResponders in Whom Breast Cancer Surgery Can BeEliminated Following Neoadjuvant Systemic Therapy .Kuerer H et al Annals of Surgery 267 5 946 951 May 2017Mammogram US MRI BiopsyAccuracy 98 NRG BR005A Phase II Trial Assessing the Accuracy of Tumor Bed.Biopsies in Predicting Pathologic Response in Patients withClinical Radiologic Complete Response after NeoadjuvantChemotherapy in Order to Explore the Feasibility of BreastConserving Treatment without Surgery Eligibility .Stage I IIINeoadjuvant ChemotherapyClinical CRTrimodalityGuided Core Lumpectomy. Primary Objective To assess the accuracy of post neoadjuvant systemictherapy image directed tumor bed biopsy for pCR in casesAt the 20-year follow-up to this trial, reported in 1995, the survival benefits of CMF versus no adjuvant therapy were confirmed. Bonadonna G, Brusamolino E, Valagussa P, et al. Combination chemotherapy as an adjuvant treatment in operable breast cancer. N . Engl. J Med. 1976;294:405-410.