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Systemic Therapy for Breast Cancer - Adjuvant or Neoadjuvant PowerPoint Presentation

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Description : Check out this medical presentation on Breast Cancer (Inflammatory), which is titled "Systemic Therapy for Breast Cancer - Adjuvant or Neoadjuvant", to know about Adjuvant and Neoadjuvant therapies for breast cancer.

Tags : Breast Cancer, Inflammatory, Systemic Therapy, Adjuvant, Neoadjuvant

Published on : May 10, 2021 | Views : 2011 | Downloads : 3

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Systemic Therapy for Breast Cancer Adjuvant or Neoadjuvant Agustin A Garcia, MD, MMM Professor of Medicine and Section Chief Hematology Oncology Charles W McMullin III and Richard Paul Grace Chair in Cancer Research Louisiana State University New Orleans, LA
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Disclosure I have the following relationship(s) with commercial interests. NAME OF COMPANY: Celldex, Seattle Genetics, Iovance RELATIONSHIP Investigator RECEIVED Grants A commercial interest is any entity producing, marketing, re-selling, or distributing health care goods or services consumed by, or used on, patients.
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Breast CancerMortality by Race
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The 20th Century: From radical to more breast-conserving surgery Winchester DP, et al. Surg Oncol Clin N Am. 2005;14:479. 1880 1900 1920 1940 1960 1980 2000 Sentinel lymph node mapping No difference in survival with radical mastectomy or lumpectomy Modified radical mastectomy Inoperability criteria established for locally advanced breast cancer Radical mastectomy and supraclavicular dissection Removal of whole breast, including pectoral muscles and axillary lymph nodes
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Advances in the Adjuvant Treatment of Breast Cancer 1980 1990 2000 2006 NSABP B14 Tamoxifen vs placebo NSABP B15 AC vs CMF NCIC MA-5 CEF vs CMF FASG 05 FEC100 vs FEC50 CALGB 9741 Dose dense AC→P Standard dose AC→P CALGB 9344 AC vs ACP NSABP B27 T→ AC vs TAC BCIRG 001 TAC vs FAC BIG 1-98 Letrozole vs tamoxifen NSABP B28 AC vs ACP EBCTCG (meta-analysis) Anthracycline-based regimen vs CMF BIG 01-01 HERA Local therapy ± trastuzumab NCCTG N9831 AC→P vs AC→P + trastuzumab vs AC→P→trastuzumab NSABP B31 AC→P vs AC→P + trastuzumab PACS-01 FEC vs FEC + T BCIRG 006 AC→T ± trastuzumab vs TCb + trastuzumab 1970 Istituto Nazionale Tumori (Milan) CMF vs placebo NSABP B05, B07 Melphalan vs placebo NSABP B08-B10 Melphalan ± 5-FU 2018 NeoSphere Chemo + Trastuzumab (T) vs Chemo + T + pertuzumab ExteNET Chemo + T vs Chemo + T →Neratinib CREATE-X TNBC Neoadjuvnant Chemo Post Capecitabine
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Adjuvant Chemotherapy: Effects on RFS, long term follow up. Bonadonna et al. N Engl J Med. 1995;332:901-906. 35% decrease in risk of recurrence. 24% decrease in risk of death P<0.04 N=386 node-positive patients.
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Adjuvant Chemotherapy Effects on RFS EBCTCG 2000, Lancet 2005
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Adjuvant Chemotherapy Effects on OS
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Multidisciplinary Management of Breast Cancer Surgical Management ↓ Systemic Therapy ↓ Radiation 5 Breast Conservation Mastectomy Radiation Chemotherapy Endocrine Therapy HER2 Targeted Tx
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Neoadjuvant Chemotherapy for Breast Cancer Historical Perspective Hortobagyi GN, Cancer 1983 Hortobagyi GN, Cancer 1988 Jacquillat C, Cancer 1990
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Neoadjuvant or PreOperative Chemotherapy Goals A) Reduce Distant Metastasis B) Select Individualized Therapy for Non Responders C) Improve surgical care Down stage Tumor Allow less extensive surgery Facilitate breast conserving surgery Improve cosmetic outcome
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Neoadjuvant or PreOperative Chemotherapy Goals A) Reduce Distant Metastasis
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Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis EBCTCG Lancet Oncol 2018
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Neoadjuvant or PreOperative Chemotherapy Goals A) Reduce Distant Metastasis B) Select Individualized Therapy for Non Responders C) Improve surgical care Down stage Tumor Allow less extensive surgery Facilitate breast conserving surgery Improve cosmetic outcome
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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
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Associations between pathological complete response and event-free survival and overall survival
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Association between pCR and event-free survival, by breast cancer subtype
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Benefits of Monitoring Efficacy to Neoadjuvant Chemotherapy: GeparTrio Trial Von Minckwits G, et al. J Clin Oncol 2013 TAC= Docetaxel, Adriamycin, Cyclophosphamide NX= Vinorelbine, Capecitabine
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GeparTrio Results
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Patients with Triple Negative Breast Cancer who do not achieve a pCR have a poor prognosis
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Post Operative Chemotherapy in Patients with Residual Disease after Neoadjuvant Therapy: CREATE-X Trial Masuda N, et al. N Engl J Med 2017
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CREATE-X: Results
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CALGB 40603: Addition of Carboplatin to Neoadjuvnat Chemotherapy in Triple Negative Breast Cancer
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CALGB 40603: Results
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What we know about the results of Neoadjuvant Chemotherapy Achieving a pCR is associated with excellent survival Patients without a pCR or poor clinical response have a poor prognosis Switching chemotherapy in poor responders leds to improve outcome The addition of carboplatin improves pCR
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Proposed Approach to Neoadjvuant Chemotherapy in Triple Negative Breast Cancer    
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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 grade Poor prognosis Killelea BK, et al. Am J Surg 2017
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4 cycles 4 cycles Dox/Cyc Pax HD q 3 wk Trastuzumab Pax HD q 3 wk 4 cycles 4 cycles 52 wks NSABP B-31 NCCTG 9831 Dox/Cyc Pax LD/wk Trastuzumab Pax LD/wk Trastuzumab Pax LD/wk 12 wks 52 wks 64 wks HERA Trastuzumab No therapy Standard ChemoRx 1 Yr 2 Yr BCIRG 006 Dox/Cyc 4 cycles Docetaxel Docetaxel Trastuzumab Docetaxel Carboplatin Trastuzumab Trastuzumab Summary of Trastuzumab Trials
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Accepted Principles of Neoadjuvant Therapy Affords outcomes identical to adjuvant therapy Improves operability of inoperable, locally advanced breast cancer Improves breast conservation rates Improves outcome in Inflammatory Breast Cancer: Standard of Care
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10 year results of adjuvant Chemotherapy + Trastuzumab 37% improvement in Survival Perez E, et al J Clin Oncol 2014
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Neoadjuvant Chemotherapy for HER2 positive Breast Cancer: NOAH Study Gianni L et al. Lancet 2010
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NOAH Trial: Results
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NEOSPHERE RESULTS
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ExteNET Results 33% Reduction in Recurrence
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What we know about the results of Neoadjuvant Chemotherapy in HER2 Pos Breast Cancer Achieving a pCR is associated with excellent survival Patients without a pCR or poor clinical response have a poor prognosis The addition of pertuzumab significantly improves pCR The addition of neratinib after trastuzumab significantly improves DFS
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Proposed Approach to Neoadjvuant Chemotherapy in HER2 postivie Breast Cancer    
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Neoadjuvant or PreOperative Chemotherapy Goals A) Reduce Distant Metastasis B) Select Individualized Therapy for Non Responders C) Improve surgical care Down stage Tumor Allow less extensive surgery Facilitate breast conserving surgery Improve cosmetic outcome
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Effects of Neoadjuvant Chemotherapy on BCT
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Challenges with Neoadjuvant Therapy
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Effects of surgery in Risk of Local Recurrence after Neoadjvuant Chemoterapy
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Considerations for Lumpectomy after Neoadjuvnat Chemotherapy 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 tumor If viable tumor is present throughout the specimen, even if it does not extend to 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)
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Management of the Axilla After Neoadjuvant Chemotherapy (NAC) NAC downstages axilla in up to 40% of patients Consider SLNB after NAC and avoid ALND? Influence of pretreatment clinical node stage
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SLN Biopsy after Neoadjuvant Chemotherapy cN1converted to CN0
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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
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Post NAC Trials of Axillary Management
cN1 to cN0 Can axillary RT replace ALND Can Response to NAC be used to select Radiation
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Is there a role for neoadjuvant endocrine therapy?
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21-Gene Recurrence Score
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Genomic Profiling to Identify Patients who do not require adjuvant chemotherapy
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Should patients with HR+, HER2 neg breast cancer receive neoadjuvant chemotherapy? Bear HD, et al. J Surg Oncol 2017
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NHT= Neoadjuvant Endocrine Therapy NCT+ Neoadjuvant Chemotherapy
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Neoadjuvant Chemotherapy: Summary and Future 40-60% of patients with triple negative or HER2 positive breast cancer 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/or radiation)? Can these patients be identified preoperatively?
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Neoadjuvant Chemotherapy: Summary and Future 40-60% of patients with triple negative or HER2 positive breast cancer 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/or radiation)? Can we avoid surgery in patients with a pCR? Can these patients be identified preoperatively?
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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
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Can we avoid surgery in patients who achieve a pCR?
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Can we avoid surgery in patients who achieve a pCR? Problem: pCR identified after surgery
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Can we avoid surgery in patients who achieve a pCR Problem pCR identified after surgery
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Imaging studies in identifying pCR Van la Parra R, et al. Breast Cancer Rest 2016
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A Clinical Feasibility Trial for Identification of Exceptional Responders in Whom Breast Cancer Surgery Can Be Eliminated Following Neoadjuvant Systemic Therapy. Kuerer H et al. Annals of Surgery. 267(5):946-951, May 2017 Mammogram + US + MRI + Biopsy Accuracy = 98% FNR= 5% NPV= 95%
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NRG BR005 A Phase II Trial Assessing the Accuracy of Tumor Bed Biopsies in Predicting Pathologic Response in Patients with Clinical/Radiologic Complete Response after Neoadjuvant Chemotherapy in Order to Explore the Feasibility of Breast Conserving Treatment without Surgery
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Eligibility: Stage I-III Neoadjuvant Chemotherapy Clinical CR
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Primary Objective To assess the accuracy of post-neoadjuvant systemic therapy image-directed tumor bed biopsy for pCR in cases of clinical and radiologic complete response with trimodality imaging.
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Aim To develop a multidisciplinary approach combining clinical exam, imaging and pathology (biopsy) to Predict pCR > 90%
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Indications for Neoadjuvant Therapy Inflammatory Breast Cancer Localized Advanced Breast Cancer Facilitate BCT Consider for all patients candidates for systemic chemotherapy: Triple negative or HER 2 + > 2 cms Don’t forget the role of neoadjuvant endocrine therapy
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Evolution of Local Management of Breast Cancer Winchester DP, et al. Surg Oncol Clin N Am. 2005;14:479. 1880 1900 1920 1940 1960 1980 2000 Sentinel lymph node mapping No difference in survival with radical mastectomy or lumpectomy Modified radical mastectomy Inoperability criteria established for locally advanced breast cancer Radical mastectomy and supraclavicular dissection Removal of whole breast, including pectoral muscles and axillary lymph nodes
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Evolution of Local Management of Breast Cancer Winchester DP, et al. Surg Oncol Clin N Am. 2005;14:479. 1880 1900 1920 1940 1960 1980 2000 2020 Sentinel lymph node mapping No difference in survival with radical mastectomy or lumpectomy Modified radical mastectomy Inoperability criteria established for locally advanced breast cancer Radical mastectomy and supraclavicular dissection Removal of whole breast, including pectoral muscles and axillary lymph nodes No Surgery?
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We’ve come a long way
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Thank You Questions?