Role of primary site local management for ABC patients    Virgilio Sacchini     Breast ServiceMemorial Sloan-KetteringCanc...
Historical arguments against surgeryin stage IV breast cancer• Patients were debilitated, bulky disease, survival  brief  ...
National Cancer Database from 1990-93                         (Khan SA, Surgery 2002)              6861 (42.8%) no operati...
National Cancer Database from 1990-93                          (Khan SA, Surgery 2002)• Comparing only surgical patients, ...
National Cancer Database from 1990-93                      (Khan SA, Surgery 2002)• Comparing only surgical patients, surv...
Current perspective - primary tumorsurgery in Stage IV Breast Cancer ??• May not respond to systemic therapy in parallel  ...
Current perspective - primary tumorsurgery in Stage IV Breast Cancer ??• May not respond to systemic therapy in parallel  ...
Studies assessing distant metastasis detected by conventional imaging              with PET/CT in patients with primary br...
Overview                    (Neuman H, Cancer 2010)Study        Type          Years              N   % surg   HRMSKCC 2011
Pooled analysis of hazard ratios for overall mortality for surgery versus no    surgery for patients with stage-IV breast ...
MSKCC Experience                  (Neuman H, Cancer 2010)•   2000-2004, database review•   186 patients stage IV•   Surger...
Predictors of Survival of Patients Presenting With Stage IV Breast Cancer                         and an Intact Primary Tu...
Local surgery in Stage IV disease    molecular subtype analysis                           Kaplan-Meier survival estimates,...
for Change in Management• Resection of the primary may improve survival• Better local control at diagnosis may  • prevent ...
Surgical resection of the primary tumor, chest wall control, and            survival in women with metastatic breast cance...
(Hazard HW, Cancer, 2008)                                      103 patients with               10 (16%)                   ...
Conclusion (Facts)• Retrospective evidence that resection the primary  tumor is associated with improved survival in selec...
Randomized trials open or starting Location      NCT        Timing             Sample SIZE India         00193778   After ...
ECOG 2108 (Seema Khan P.I.)      Register 880 women     Optimal systemic therapy   70% response/stable disease    Randomiz...
What do we know about          surgical timing ?                   Surgery before vs. after      Significant              ...
Conclusion (what to do now?)            When Surgery Reasonable•   Good response to metastatic sites/non    response-progr...
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ABC1 - V. Sacchini - Role of primary site local management for advanced breast cancer patients

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  • Pooled analysis of hazard ratios for overall mortality for surgery versus no surgery for patients with stage-IV breast cancer
  • ABC1 - V. Sacchini - Role of primary site local management for advanced breast cancer patients

    1. 1. Role of primary site local management for ABC patients Virgilio Sacchini Breast ServiceMemorial Sloan-KetteringCancer Center - New York
    2. 2. Historical arguments against surgeryin stage IV breast cancer• Patients were debilitated, bulky disease, survival brief • Avoid morbidity for unknown benefit• Measurable disease: can be followed for response• Fear that removal of the primary tumor would result in increased angiogenesis and stimulation of dormant disease
    3. 3. National Cancer Database from 1990-93 (Khan SA, Surgery 2002) 6861 (42.8%) no operation16,023 withStage IV 9162 (57.2%) partial mastectomy or total mastectomy Survival No surgery
    4. 4. National Cancer Database from 1990-93 (Khan SA, Surgery 2002)• Comparing only surgical patients, survival advantage for those with clear margins (for both total mastectomy and partial mastectomy) Survival for Total Mastectomy Patients Clear margins Complete excision better then the debulking
    5. 5. National Cancer Database from 1990-93 (Khan SA, Surgery 2002)• Comparing only surgical patients, survival advantage for those with clear margins (for both total mastectomy and partial mastectomy) 5 year survival No operation 6.7% Involved Margins Partial Mast 11.3% Total Mast 11.5% Clear Margins Partial Mast 16.6% Total Mast 18.4% Conclusion: complete surgical extirpation of the Cancer is associated with improved survival
    6. 6. Current perspective - primary tumorsurgery in Stage IV Breast Cancer ??• May not respond to systemic therapy in parallel with metastatic sites ? • grow locally and lead to uncontrolled chest wall disease and impaired quality of life• May serve as a continued source of tumor stem cells? • lead to new metastatic lesions which are resistant to systemic therapy• More “earlier stage 4”
    7. 7. Current perspective - primary tumorsurgery in Stage IV Breast Cancer ??• May not respond to systemic therapy in parallel with metastatic sites ? • grow locally and lead to uncontrolled chest wall disease and impaired quality of life• More “earlier stage 4”
    8. 8. Studies assessing distant metastasis detected by conventional imaging with PET/CT in patients with primary breast cancer Patients with Patients with distant distant Patient metastases First author Type of study No. patients metastases population detected by detected by conventional PET/CT No. (%) imaging No. (%) Primary tumor Fuster D Prospective 60 3 (5) 8 (13) >3 cm Carkaci S Retrospective Primary IBC 41 13 (32) 20 (49) Alberini J Prospective Primary IBC 62 12 (19) 18 (29) Suspected Heusner T Retrospective 40 7 (18) 10 (25) breast cancer Groheux D Retrospective Stage II and III 39 0 4 (10)Stage IIA Upstaged IV in 5.5% Do we under-treat these early stage IV?)Naoki Niikura, Naoto T. Ueno J Cancer 2010
    9. 9. Overview (Neuman H, Cancer 2010)Study Type Years N % surg HRMSKCC 2011
    10. 10. Pooled analysis of hazard ratios for overall mortality for surgery versus no surgery for patients with stage-IV breast cancer•10 studies, mostly database or registry driven, with over 30,000 patients studied, about50% of them had resection of primary•With all the biases, most studies show some survival benefit in patients having surgery Jetske Ruiterkamp et Al: Breast Cancer Research and Treatment, 2010
    11. 11. MSKCC Experience (Neuman H, Cancer 2010)• 2000-2004, database review• 186 patients stage IV• Surgery 69 (37%) – No surgery 117 (63%)• Median f/u 53 months• Improvement in median survival from 33months to 40months
    12. 12. Predictors of Survival of Patients Presenting With Stage IV Breast Cancer and an Intact Primary Tumor No. Hazard Ratio 95% CI PSurgeryResection 69 (37%) 0.71 0.47-1.1 .10No resection ReferenceER statusPositive 127 (68%) 0.47 0.29-0.76 .002Negative ReferencePR statusPositive 74 (40%) 0.57 0.37-0.90 .02Negative ReferenceHER-2/neuAmplified 59 (32%) 0.51 0.34-0.77 .001Not amplified ReferenceAge at stage IV 1.0 0.98-1.01 .73diagnosisSolitary metastasisYes 24 (13%) 1.2 0.62-2.4 .57No ReferenceBone metastasesYes 122 (66%) 1.7 1.1-2.8 .02No ReferenceVisceral metastasesYes 111 (60%) 2.3 1.4-3.6 <.001No Reference
    13. 13. Local surgery in Stage IV disease molecular subtype analysis Kaplan-Meier survival estimates, by surgery triple_neg 1.00 p = 0.004 0.75 Not 0.50 Triple negative 0.25 p=0.44 Triple negative 0.00 0 20 40 60 analysis time surgery = 0/triple_neg = 0 surgery = 0/triple_neg = 1 surgery = 1/triple_neg = 0 surgery = 1/triple_neg = 1Surgery had a benefit in non-triple negativeSurgery had no benefit in triple negativeConclusion: resection of the primary in stage IV breast cancer is associatedwith improved survival in some molecular subtypes Neuman H et al. Cancer 2010
    14. 14. for Change in Management• Resection of the primary may improve survival• Better local control at diagnosis may • prevent wound problems in future • decrease symptoms due to chest wall disease • better quality of life
    15. 15. Surgical resection of the primary tumor, chest wall control, and survival in women with metastatic breast cancerMethods: Lynn Sage, Northwestern Memorial Databases from 1995-2005, withstage IV with intact primary, 27month median f/u, 103 Pts with chest wall information 44 surgery 59 no surgery H Hazard et Al, Cancer 2008
    16. 16. (Hazard HW, Cancer, 2008) 103 patients with 10 (16%) chest wall info palliative surgery 44 surgery 59 no surgery 13 (21%) palliative radiationChest wall/breast free 36 (82%) 20 (24%) p=0.002Symptomatic chest dz 8 (18%) 29 (49%) p=0.002 Conclusion: Nearly half of patients who do not have primaryresected, will become symptomatic. Early resection can significantlydecrease chest wall/ breast symptoms.
    17. 17. Conclusion (Facts)• Retrospective evidence that resection the primary tumor is associated with improved survival in selected Pts• Chest wall symptoms can be improved with resection of the primary• Basic science evidence suggesting that resection of the primary may decrease re-seeding For definitive change in standard of care, prospective randomized trials are needed.
    18. 18. Randomized trials open or starting Location NCT Timing Sample SIZE India 00193778 After 6 cycle CH 350 Turkey 00557986 Before CH 271 Austria 01015625 Before CH 254 Netherlands 01392586 Before CH 516 USA 01242800 After 6 cycle CH 616 ECOG 2108
    19. 19. ECOG 2108 (Seema Khan P.I.) Register 880 women Optimal systemic therapy 70% response/stable disease Randomize 616 womenPalliative local Elective local therapy therapy, 308 308
    20. 20. What do we know about surgical timing ? Surgery before vs. after Significant chemotherapy (n) surgery benefit ?Boston (Bafford) 36 vs. 24 BeforeBoston (Cady) 30 vs. 45 BothMDACC (Rao) 47 vs. 28 After Chicago 26 vs. 21 Both (Hazard)
    21. 21. Conclusion (what to do now?) When Surgery Reasonable• Good response to metastatic sites/non response-progression to the primary• “one almost positive” (ER+/HER2+) with response to the treatment• Minimal Stage 4• Chest wall recurrence without distant metastasis or good response to the distant mets

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