“Examining Advances in Management of Breast Cancer  During the Last 30 Years”LOCAL REGIONAL TREATMENT7th Annual Breast Hea...
OUTLINE   Trends in breast cancer surgery   Tension between BCS and total mastectomy         Evolution to breast conser...
Death rates decreased 31% between 1989 and 2007
5 YEAR RELATIVE SURVIVAL RATES                      BREAST CANCER: 1996                                   to 2005         ...
Trends in BreastCancer Surgery
Trends in Breast Cancer SurgeryBREAST CONSERVATION THERAPY:LONG-TERM VALIDATION OF SAFETY
SURVIVAL IN RANDOMIZED TRIALS OFBREAST CONSERVATION VS. MASTECTOMY 90% 80% 70% 60% 50%                                    ...
20 YEAR FOLLOW-UP OF BREAST     CONSERVATION RANDOMIZED TRIALS:              OVERALL SURVIVALNEJM 2002; 347: 1227-32 & 123...
20 YEAR FOLLOW-UP OF RANDOMIZED    BREAST CONSERVATION TRIALS:         LOCAL RECURRENCENEJM 2002; 347: 1227-32 & 1233-41 C...
PATTERN OF LOCALRECURRENCE OVER TIME: B-06TOTALLR        < 5 YRS 5-10 YRS >10 YRS78EVENTS     40%      29%     31%(14.3%)
LOCAL RECURRENCE IN     RECENT BCT TRIALS NSABP trials since B-06 show lower  rates of LR 6% LR at 10 years in node nega...
NIH CONSENSUS CONFERENCE    ON EARLY STAGE BREAST         CANCER: 1990 Outcomes of breast conserving  surgery similar to ...
INCREASING UTILIZATION OF      BREAST CONSERVATION OVER TIME                                              68%             ...
WHY WOMEN DECLINEBREAST CONSERVATION Fear of radiation Disbelief in radiation efficacy Inconvenience of prolonged and  ...
TREND TOWARD MORE AGGRESSIVE      SURGICAL TREATMENT SEER   1998-2003• 152,755 patients with stage I-III  breast cancer ...
Contralateral Prophylactic Mastectomy (CPM):           Increased Use in U.S.   CPM increased from 4% to 11 % of all    pa...
More likely to have contralateralmastectomy if:       Young       White race       More favorable tumors       Women w...
Bilateral Mastectomy Rate INCREASED                 FROM 0% TO 10% from 1997-2007             12%             10%PERCENTAG...
ASSISTING WOMEN IN DECISION MAKING           FOR MASTECTOMY OR NOT?   Inform in unbiased way about options- data    drive...
AXILLARY STAGING:               SENTINEL NODE BIOPSYMINIMIZING NODAL SURGERYHas replaced ALND as standard for nodal staging
HISTORY OF AXILLARY STAGING    FOR BREAST CANCER Formal axillary node dissection levels  2-3 standard of care for decades...
RATIONALE FOR LYMPHATIC MAPPING    AND SENTINEL NODE BIOPSY    Axillary dissection carries morbidity of     lymphedema, d...
SUMMARY OF SENTINEL NODE       BIOPSY SERIES DATA False negative rate 0-12% Success in identification of sentinel  node ...
WHAT WE HAVE LEARNED      FROM CLINICAL TRIALS   ACOSOG Z0010- ? significance of IHC    occult mets   NSABP B32- ? Safet...
ACOSOG Z10 TRIAL             Giuliano, A. E. et al. JAMA 2011;306:385-393To identify: Prevalence and prognostic significa...
ACOSOG Z10 METHODS   5,539 patients (4/1999 - 5/2003)   Breast conserving surgery, Bone marrow aspiration and    sentine...
SURGICAL TECHNICAL OUTCOMES: Z0010Using a standard skill requirement surgeonsachieved a low SLN failure rate  98.7% SLN ...
ACOSOG Z10: FINDINGS   Sentinel Lymph node data     H&E:   24% positive for metastases     IHC: 10% of cases with micro...
Bone Marrow Specimen Results and Cumulative Incidence of Death                                              Median follow-...
Sentinel Lymph Node Results and Cumulative Incidence of Death                                                   NO DIFFERE...
Conclusions from ACOSOG Z10   Outcome in this population was EXCELLENT- 5 year    overall survival of 93% in patients wit...
NSABP B-32:   Largest prospective randomized phase III    trial of SLND alone vs SLND +ALND for    sentinel node negative...
Kaplan-Meier Survival Estimates According to the Presence or Absence of Occult Metastases                   Detected in In...
NSABP B32 Conclusions• Significant difference overall survival between patients  with IHC occult metastases and those in w...
COMPARISON ACOSOG Z10     AND NSABP B32                    ACOSOG Z10   NSABP B32Tumor size            1.4cmT1            ...
MANAGEMENT OF THE POSITIVE     SENTINEL NODE Standard     of care :   Axillary   Lymph Node Dissection Is   ALND necess...
RATIONALE TO AVOID ALND IN   SLN POSITIVE PATIENTS SLN  often the only positive node Adjuvant therapy may treat  subclin...
ACOSOG Z0011A randomized trial of axillary node dissection  VS no axillary dissection in women with  clinical T1-2 N0 M0 b...
ACOSOG Z11 RESULTS:      REPORTED ASCO 6/2010 106 (27.4%) patients undergoing ALND hadadditional positive nodes removed b...
Locoregional Recurrence-Free Survival                 40
Summary     Locoregional Recurrence-Free Survival   Locoregional recurrence in only 2.8% of    SLND and 4.1% of ALND pati...
Overall Survival          100          90          80          70          60% Alive          50          40          30  ...
Summary         Disease-Free and Overall Survival   No significant difference in DFS between    patients treated with SLN...
Z11 ConclusionIn this prospectiverandomized study - SLNDalone provided excellentlocoregional control andsurvival comparabl...
REMEMBER: APPLIES TO      SELECTED PATIENTS•   Initially clinically node negative•   Patients having breast conserving    ...
ACOSOG Z10 AND Z11/ NSABP B32      PRACTICE CHANGING•   Abandon use of IHC to evaluate    sentinel nodes•   Abandon ALND f...
THANK YOU
EVOLVING ROLE OF RADIATION IN BREAST CANCER MANAGEMENT   After breast conserving surgery     Whole breast radiation    ...
Value of Local Control for Survival             Lancet 366:2087, 2005 Oxford  overview 2005 Node positive breast cancer ...
OVERCOMING RADIATION    CONCERNS: ACCELERATED    PARTIAL BREAST RADIATION    Vicini, J Clin Oncol 2001;19:1993-2001,    Br...
INITIAL CRITERIA FOR SELECTING     PATIENTS FOR PARTIAL BREAST            RADIATION (PBI)                     ABS         ...
ACCELERATED PARTIAL BREAST IRRADIATION       CONSENSUS STATEMENT FROM   THE AMERICAN SOCIETY FOR RADIATION          ONCOLO...
COMPARATIVE CRITERIA FOR     SELECTING PATIENTS FOR PARTIAL          BREAST RADIATION (PBI)                     ABS       ...
Breast Cancer Statistics, 2011 : Trends in Female Breast             Cancer Death Rates by Race and Ethnicity, 1975 to 200...
Overall Survival by Bone Marrow IHC          100           90           80           70           60% Alive           50  ...
Associations of Prognostic Variables       with Overall Survival                     Univariable Analysis   Multivariable ...
Local Regional Treatment: Examining Advances in Management of Breast Cancer, Dr. Marilyn Leitch - 7th Annual Breast Health...
Local Regional Treatment: Examining Advances in Management of Breast Cancer, Dr. Marilyn Leitch - 7th Annual Breast Health...
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Local Regional Treatment: Examining Advances in Management of Breast Cancer, Dr. Marilyn Leitch - 7th Annual Breast Health Summit

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Local Regional Treatment: Examining Advances in Management of Breast Cancer, Dr. Marilyn Leitch - 7th Annual Breast Health Summit

  1. 1. “Examining Advances in Management of Breast Cancer During the Last 30 Years”LOCAL REGIONAL TREATMENT7th Annual Breast Health Summit Houston, TX 10/21/2011 A. Marilyn Leitch, MD Professor of Surgery UT Southwestern
  2. 2. OUTLINE Trends in breast cancer surgery Tension between BCS and total mastectomy  Evolution to breast conserving surgery  Increasing rate of bilateral mastectomies Adoption of Sentinel node biopsy of nodal staging Abandonment of ALND for positive sentinel node
  3. 3. Death rates decreased 31% between 1989 and 2007
  4. 4. 5 YEAR RELATIVE SURVIVAL RATES BREAST CANCER: 1996 to 2005 SEER Data (CA Cancer J Clin 2010) 99 93 98 100 85 84 80Percentage % 72 60 40 25 23 20 17 0 LOCAL REGIONAL DISTANT WHITE AFRICAN AMERICAN ALL RACES
  5. 5. Trends in BreastCancer Surgery
  6. 6. Trends in Breast Cancer SurgeryBREAST CONSERVATION THERAPY:LONG-TERM VALIDATION OF SAFETY
  7. 7. SURVIVAL IN RANDOMIZED TRIALS OFBREAST CONSERVATION VS. MASTECTOMY 90% 80% 70% 60% 50% MAST 40% BCT 30% 20% 10% 0% Gustave- Milan NSABP NCI EORTC Danish Roussy
  8. 8. 20 YEAR FOLLOW-UP OF BREAST CONSERVATION RANDOMIZED TRIALS: OVERALL SURVIVALNEJM 2002; 347: 1227-32 & 1233-41 CANCER 2003;98 697-702
  9. 9. 20 YEAR FOLLOW-UP OF RANDOMIZED BREAST CONSERVATION TRIALS: LOCAL RECURRENCENEJM 2002; 347: 1227-32 & 1233-41 CANCER 2003;98 697-702
  10. 10. PATTERN OF LOCALRECURRENCE OVER TIME: B-06TOTALLR < 5 YRS 5-10 YRS >10 YRS78EVENTS 40% 29% 31%(14.3%)
  11. 11. LOCAL RECURRENCE IN RECENT BCT TRIALS NSABP trials since B-06 show lower rates of LR 6% LR at 10 years in node negative patients Attributed to use of adjuvant systemic therapy NEJM 2002;347:1233-41
  12. 12. NIH CONSENSUS CONFERENCE ON EARLY STAGE BREAST CANCER: 1990 Outcomes of breast conserving surgery similar to mastectomy in randomized trials Breast conservation therapy is the preferred treatment for most stage I and II breast cancers
  13. 13. INCREASING UTILIZATION OF BREAST CONSERVATION OVER TIME 68% 69%70% 58%60% 49%50% 46%40% 35% 36%30% 19%20%10%0% 1985-89 1995 2000 2007 Stage I Stage IICancer 1999; 86: 628-37 / Cancer 1998;83:1262-73 / Commission on CancerBenchmark Reports 9/2003, 9/2010
  14. 14. WHY WOMEN DECLINEBREAST CONSERVATION Fear of radiation Disbelief in radiation efficacy Inconvenience of prolonged and daily radiation treatments Lack of radiation treatment facility nearby Disbelief in equivalency to mastectomy for survival Strong family history breast cancer
  15. 15. TREND TOWARD MORE AGGRESSIVE SURGICAL TREATMENT SEER 1998-2003• 152,755 patients with stage I-III breast cancer 3.3% (4969) had contralateral Prophylactic Mastectomy (PM) contralateral PM increased from 1.8% to 4.5%
  16. 16. Contralateral Prophylactic Mastectomy (CPM): Increased Use in U.S. CPM increased from 4% to 11 % of all patients having mastectomy 150% increase in opposite breast mastectomy over 1998-2003 when treated for Invasive breast cancer in one breast
  17. 17. More likely to have contralateralmastectomy if:  Young  White race  More favorable tumors  Women with previous history of other cancer  Infiltrating lobular cancer
  18. 18. Bilateral Mastectomy Rate INCREASED FROM 0% TO 10% from 1997-2007 12% 10%PERCENTAGE 8% 6% 4% 2% 0% 1996 1998 2000 2002 2004 2006 2008 YEARUT SOUTHWESTERN EXPERIENCE
  19. 19. ASSISTING WOMEN IN DECISION MAKING FOR MASTECTOMY OR NOT? Inform in unbiased way about options- data driven Discuss alternatives that make lumpectomy without opposite mastectomy less worrisome  Adjuvant therapy taken after surgery  Enhanced surveillance with MRI  Lifestyle risk reduction strategies ONCOPLASTIC ALTERNATIVES for making saved breast more attractive and matching opposite breast  Insurance covers these procedures
  20. 20. AXILLARY STAGING: SENTINEL NODE BIOPSYMINIMIZING NODAL SURGERYHas replaced ALND as standard for nodal staging
  21. 21. HISTORY OF AXILLARY STAGING FOR BREAST CANCER Formal axillary node dissection levels 2-3 standard of care for decades NSABP B04 trial showed ALND not associated with improved survival With smaller tumors detected in mammography screening, less node positive Thus nodes removed unnecessarily
  22. 22. RATIONALE FOR LYMPHATIC MAPPING AND SENTINEL NODE BIOPSY  Axillary dissection carries morbidity of lymphedema, decreased ROM and decreased sensation of upper inner arm  The status of the axillary nodes is the most important prognostic feature for breast cancer  If axilla accurately staged with a sentinel node biopsy which removes few nodes, then less morbidity of staging procedure
  23. 23. SUMMARY OF SENTINEL NODE BIOPSY SERIES DATA False negative rate 0-12% Success in identification of sentinel node 70-100%, with most series better than 90% success Higher success in SLN identification and lower false negative rates (<5%) in series with more experience
  24. 24. WHAT WE HAVE LEARNED FROM CLINICAL TRIALS ACOSOG Z0010- ? significance of IHC occult mets NSABP B32- ? Safety of SLND compared to ALND ACOSOG Z0011- role of ALND for positive sentinel node
  25. 25. ACOSOG Z10 TRIAL Giuliano, A. E. et al. JAMA 2011;306:385-393To identify: Prevalence and prognostic significance of sentinel lymph node (SLN) micrometastases and bone marrow (BM) micrometastases detected by immunohistochemistry (IHC)• Assess risk of regional recurrence for SLN negative by H&E• Assess operative morbidity Women with clinical T1-T2N0M0 breast cancer
  26. 26. ACOSOG Z10 METHODS 5,539 patients (4/1999 - 5/2003) Breast conserving surgery, Bone marrow aspiration and sentinel node biopsy Bone marrow specimens examined with IHC (investigators blinded to results) SLNs processed by standard pathology with H&E staining SLNs negative by H&E examined with IHC for cytokeratin (investigators blinded to results) H&E node positive patients-  Axillary node dissection (ALND) or  Randomized on ACOSOG Z0011 study to no further surgery or ALND
  27. 27. SURGICAL TECHNICAL OUTCOMES: Z0010Using a standard skill requirement surgeonsachieved a low SLN failure rate  98.7% SLN identification ratePosther KE et al: Annals of Surgery 2005Low complication rate for SLN dissection withdefined incidence of lymphedema  1-7% rate of various axillary complications  7% rate of lymphedemaWilke LG et al: Annals of Surg Oncology 2006
  28. 28. ACOSOG Z10: FINDINGS Sentinel Lymph node data  H&E: 24% positive for metastases  IHC: 10% of cases with micrometastases  Increasing breast tumor size is associated with positive SLN Bone marrow data – n= 3,413  ICC:3% micrometastases  NO relationship to breast tumor size
  29. 29. Bone Marrow Specimen Results and Cumulative Incidence of Death Median follow-up 6.3 yrs Giuliano, A. E. et al. JAMA 2011;306:385-393Copyright restrictions may apply.
  30. 30. Sentinel Lymph Node Results and Cumulative Incidence of Death NO DIFFERENCE Giuliano, A. E. et al. JAMA 2011;306:385-393Copyright restrictions may apply.
  31. 31. Conclusions from ACOSOG Z10 Outcome in this population was EXCELLENT- 5 year overall survival of 93% in patients with H&E+ SLN Occult SLN metastases detected by IHC not associated with overall survival differences (95.7% IHC negative and 95.1% for IHC positive) Occult bone marrow metastases were significantly associated with increased mortality Routine IHC examination of H&E–negative SLNs and bone marrow is not clinically warranted for early-stage (clinical T1-T2N0) breast cancer. Incidence BMA+ was too low to recommend incorporating bone marrow aspiration biopsy into routine practice for patients with clinical T1,2 N0M0 breast cancer
  32. 32. NSABP B-32: Largest prospective randomized phase III trial of SLND alone vs SLND +ALND for sentinel node negative 5,611 women with operable, clinically N0 Median follow-up 95 mos
  33. 33. Kaplan-Meier Survival Estimates According to the Presence or Absence of Occult Metastases Detected in Initially Negative Sentinel Lymph Nodes. Weaver DL et al. N Engl J Med 2011;364:412-421
  34. 34. NSABP B32 Conclusions• Significant difference overall survival between patients with IHC occult metastases and those in whom no occult metastases were detected (94.6% and 95.8%)• Occult metastases were an independent prognostic variable in patients with sentinel nodes that were negative on initial examination; however, the magnitude of the difference in outcome at 5 years was small (1.2 percentage points)• Data do not indicate a clinical benefit of additional evaluation with IHC for initially negative sentinel nodes in patients with breast cancer.
  35. 35. COMPARISON ACOSOG Z10 AND NSABP B32 ACOSOG Z10 NSABP B32Tumor size 1.4cmT1 83% 80%H&E pos SLNS 24% 26%IHC pos SLNS 10.5% 15.9%BMA positive 3% NASystemic Adjuvant 86% 78%
  36. 36. MANAGEMENT OF THE POSITIVE SENTINEL NODE Standard of care :  Axillary Lymph Node Dissection Is ALND necessary?
  37. 37. RATIONALE TO AVOID ALND IN SLN POSITIVE PATIENTS SLN often the only positive node Adjuvant therapy may treat subclinical nodal metastases Most data indicate that ALND does not improve survival ALND is for staging
  38. 38. ACOSOG Z0011A randomized trial of axillary node dissection VS no axillary dissection in women with clinical T1-2 N0 M0 breast cancer who have a positive SN Target accrual 1900 patients (non-inferiority) • 4/1999 - 12/2004 • Closed early with 891 pts 38
  39. 39. ACOSOG Z11 RESULTS: REPORTED ASCO 6/2010 106 (27.4%) patients undergoing ALND hadadditional positive nodes removed beyond SN Median follow-up = 6.3 years Regional NODAL recurrence seen in only 0.7% of the entire population
  40. 40. Locoregional Recurrence-Free Survival 40
  41. 41. Summary Locoregional Recurrence-Free Survival Locoregional recurrence in only 2.8% of SLND and 4.1% of ALND patients Only age (< 50) and higher Bloom- Richardson score were associated with locoregional recurrence by multivariable analysis Locoregional recurrence not related to number of positive SNs, size of SN metastasis, or number of lymph nodes removed 41
  42. 42. Overall Survival 100 90 80 70 60% Alive 50 40 30 20 ALND No ALND P-value = 0.25 10 0 0 1 2 3 4 5 6 7 8 42 Time (Years)
  43. 43. Summary Disease-Free and Overall Survival No significant difference in DFS between patients treated with SLND (83.9%) or ALND (82.2%) No significant difference in OS between patients treated with SLND (92.5%) or ALND (91.8%) Only older age, ER-, and lack of adjuvant systemic therapy - NOT OPERATION - were associated with worse OS by multivariable analysis. 43
  44. 44. Z11 ConclusionIn this prospectiverandomized study - SLNDalone provided excellentlocoregional control andsurvival comparable tocompletion ALND for SLNnode positive patients
  45. 45. REMEMBER: APPLIES TO SELECTED PATIENTS• Initially clinically node negative• Patients having breast conserving surgery + radiation • MASTECTOMY PATIENTS EXCLUDED• < 2 positive SLNs and no gross extranodal extension
  46. 46. ACOSOG Z10 AND Z11/ NSABP B32 PRACTICE CHANGING• Abandon use of IHC to evaluate sentinel nodes• Abandon ALND for positive sentinel node
  47. 47. THANK YOU
  48. 48. EVOLVING ROLE OF RADIATION IN BREAST CANCER MANAGEMENT After breast conserving surgery  Whole breast radiation  Accelerated partial breast radiation After mastectomy  Positive margin  >3 positive nodes  Tumor > 5 cm with positive nodes  Stage III  Controversial: 1-3+ nodes
  49. 49. Value of Local Control for Survival Lancet 366:2087, 2005 Oxford overview 2005 Node positive breast cancer treated with mastectomy, radiation reduced local recurrence from 29% to 8% at 15 years 5% increase in overall survival for node positive with radiation
  50. 50. OVERCOMING RADIATION CONCERNS: ACCELERATED PARTIAL BREAST RADIATION Vicini, J Clin Oncol 2001;19:1993-2001, Brachytherapy 1 (2002) 184–190 Administer radiation to lumpectomy site ONLY instead of whole breast Treatment complete in 4-5 days instead of 5-7 weeks Alternative methods of local radiation:  Internal devices  External beam Limited to specific circumstances Clinical trial at UT Southwestern for Cyberknife application of PBI
  51. 51. INITIAL CRITERIA FOR SELECTING PATIENTS FOR PARTIAL BREAST RADIATION (PBI) ABS ASBSAGE >45 >50HISTOLOGY Solitary tumor, Invasive orNode negative invasive ductal in situ ductalTumor size < 3 cm < 2 cmMargins Negative > 2 mm
  52. 52. ACCELERATED PARTIAL BREAST IRRADIATION CONSENSUS STATEMENT FROM THE AMERICAN SOCIETY FOR RADIATION ONCOLOGY (ASTRO) 2009- Defined Suitable candidates – age > 60 At variance with prior guidelines Cautionary – age 50-59yrs Unsuitable - < 50 yrs
  53. 53. COMPARATIVE CRITERIA FOR SELECTING PATIENTS FOR PARTIAL BREAST RADIATION (PBI) ABS ASBS ASTROAGE >45 >50 > 60HISTOLOGY Solitary tumor, Invasive ductal Invasive ductalNode negative invasive ductal DCIS no DCISTumor size < 3 cm < 2 cm < 2cmMargins Negative > 2 mm > 2 mm
  54. 54. Breast Cancer Statistics, 2011 : Trends in Female Breast Cancer Death Rates by Race and Ethnicity, 1975 to 2007CA: A Cancer Journal for Clinicianspages n/a-n/a, 3 OCT 2011 DOI: 10.3322/caac.20134http://onlinelibrary.wiley.com/doi/10.3322/caac.20134/full#fig3
  55. 55. Overall Survival by Bone Marrow IHC 100 90 80 70 60% Alive 50 40 30 P-value = 0.01 20 Negative 10 Positive 0 0 1 2 3 4 5 6 7 8 9 10 Time in Years
  56. 56. Associations of Prognostic Variables with Overall Survival Univariable Analysis Multivariable Analysis P value P valueTreatment Arm NS NSAge (< 50, > 50) 0.002 0.006ER status 0.012 0.013PR status NS NS# Positive Total LN 0.044 NSLVI present vs. absent NS NSHistologic Type NS NSSN Metastasis Size NS NSTumor Size 0.042 NSAdjuvant Systemic Therapy 0.020 0.025Grade NS NS 58
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