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Faina Nakhlis
Division of Surgical Oncology
Dana Farber Cancer Institute
September 24, 2016
The Role of Surgery in Metasta...
Outline
•Palliative surgery for MBC
• Symptomatic intact primary site
• Local and/or regional recurrence
•Surgery in the a...
Incidence of De Novo Stage IV Breast Cancer in the US (SEER)
De Meglio et al, Breast Cancer Res Treatment, 2016
What is the Role of Palliative Surgery?
Complex Resections of Advanced Primary or Recurrent Disease
Feasible* but what are the endpoints?
*Veronesi et al, The Bre...
Goals of Palliative Surgery
(Overview of Published Literature – 1990-1994)
Pain Control (12%)
Quality of Life (17%)
Morbid...
Surgical Palliation for Symptom Control or Quality of
Life Improvement
Miner et al, Ann Surgery, 2004
Palliative procedure...
How Symptomatic is Local Disease?
MSKCC Experience* - June 2001 – July 2003
Median follow-up after intervention – 75 month...
Primary Local Therapy (PLT) for Stage IV LABC
(SEER Medicare, N=5111, 2005-2010)
Fairweather et al, SABCS 2015
Total Cohor...
Is Palliative Surgery Justified in the Setting of Stage IV Breast Cancer?
Pain Control - Yes
Quality of Life - Yes
Morbidi...
Patients with Stage IV Breast Cancer and
Asymptomatic Intact Primary Site
Do Patients with Stage IV Breast Cancer Live Longer with
Their Disease?
*Chia et al, Cancer 2007
Kaplan-Meier Overall Surv...
Systemic Therapy Utilization
Chia et al, Cancer 2007
Cox Regression Analysis for Survival in Stage IV Breast Cancer
Chia et al, Cancer 2007
Improved Disease Specific Survival
SEER, 1973-2010*
*Park et al, JCO 2015
A <3 years from diagnosis
B >5 years from diagno...
Does Surgery in Stage IV Breast Cancer Improve Survival?
Meta-analysis of Retrospective Data*
Overall Mortality – Surgery ...
How can Surgery Impact Survival in Stage IV Breast Cancer:
“Theories”
Control of seeding from
primary tumor site1
Decrease...
*King et al, ASCO 2016
A Prospective Analysis of Surgery and Survival in Stage IV
Breast Cancer (TBCRC 013)*
Cohort A (N=1...
*King et al, ASCO 2016
A Prospective Analysis of Surgery and Survival in Stage IV
Breast Cancer (TBCRC 013)*
Responders
(N...
*King et al, ASCO 2016
A Prospective Analysis of Surgery and Survival in Stage IV
Breast Cancer (TBCRC 013)*
Responders Su...
TBCRC 013
Prognostic Impact of 21-Gene Recurrence Score in Patients
With Stage IV Breast Cancer*
*King et al, JCO 2016
•Pr...
TBCRC 013
Clinical Characteristics and the 21-Gene Recurrence Score in Patients With
Stage IV Breast Cancer*
*King et al, ...
TBCRC 013
21-Gene RS vs. Time to First Progression and 2 Year Overall Survival*
*King et al, JCO 2016
TBCRC 013
Median Time to Progression and 2 Year Overall Survival in Patients with De
Novo Stage IV Breast Cancer*
*King et...
Prospective Randomized Trials
Country
Accrual
Period
N Initial Therapy Radiotherapy Status
India 2005-2012 350 Chemotherap...
Locoregional Treatment versus No Treatment of the Primary Tumour in
Metastatic Breast Cancer: an Open-Label Randomized Con...
Locoregional Treatment versus No Treatment of the Primary Tumour in
Metastatic Breast Cancer: an Open-Label Randomized Con...
Locoregional Treatment versus No Treatment of the Primary Tumour in
Metastatic Breast Cancer: an Open-Label Randomized Con...
Locoregional Treatment versus No Treatment of the Primary Tumour in
Metastatic Breast Cancer: an Open-Label Randomized Con...
A Randomized Controlled Trial Evaluating Resection of the Primary
Breast Tumor in Women Presenting with De Novo Stage IV B...
Median Overall Survival
Turkish Study (Protocol MF07-01)*
*Soran et al, ASCO 2016
Hazard Ratio P
LRS vs. ST 0.66 (95% CI 0...
Is Definitive Local Therapy Justified in the
Asymptomatic Stage IV Breast Cancer Patient?
•Possibly for those with a drama...
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The Role of Surgery in Metastatic Breast Cancer (MBC)

How surgery plays a role in the treatment of patients with metastatic breast cancer.

The Role of Surgery in Metastatic Breast Cancer (MBC)

  1. 1. Faina Nakhlis Division of Surgical Oncology Dana Farber Cancer Institute September 24, 2016 The Role of Surgery in Metastatic Breast Cancer (MBC)
  2. 2. Outline •Palliative surgery for MBC • Symptomatic intact primary site • Local and/or regional recurrence •Surgery in the asymptomatic patient with MBC
  3. 3. Incidence of De Novo Stage IV Breast Cancer in the US (SEER) De Meglio et al, Breast Cancer Res Treatment, 2016
  4. 4. What is the Role of Palliative Surgery?
  5. 5. Complex Resections of Advanced Primary or Recurrent Disease Feasible* but what are the endpoints? *Veronesi et al, The Breast 2007
  6. 6. Goals of Palliative Surgery (Overview of Published Literature – 1990-1994) Pain Control (12%) Quality of Life (17%) Morbidity and Mortality (61%) Survival (64%) “Prophylactic” Palliation (59%) Cost Effectiveness (2%) Physiologic Response (69%) Miner et al, Am J Surg 1999
  7. 7. Surgical Palliation for Symptom Control or Quality of Life Improvement Miner et al, Ann Surgery, 2004 Palliative procedures (N=823) Improved symptoms (N=659, 80%) Symptom free (N=303, 46%), median 135 days Additional symptoms (N=191, 29%) median 58 days Recurrent symptoms (N=165, 25%) Median 52 days No improvement (N=164, 20%)
  8. 8. How Symptomatic is Local Disease? MSKCC Experience* - June 2001 – July 2003 Median follow-up after intervention – 75 months Symptom relief: •30 days – 91% •100 days – 81 % Stage IV breast cancer, N=91 (de novo – N=20, 22%) Palliative procedures, N=109 (Mastectomies, N=3, 3%) Additional procedures, N=60, 60% *Morrough et al, Cancer 2010
  9. 9. Primary Local Therapy (PLT) for Stage IV LABC (SEER Medicare, N=5111, 2005-2010) Fairweather et al, SABCS 2015 Total Cohort (N=5111) Asymptomatic (N=4645, 91%) PLT (N=1294, 28%) Asymptomatic (N=998, 81%) New symptoms (N=246, 19%) No PLT (N=3351, 72%) Asymptomatic (N=3003, 90%) New symptoms (N=348, 10%) Symptomatic (N=466, 9%) PLT (N=118, 25%) Asymptomatic (N=57, 48%) New/recurrent symptoms (N=61, 52%) No PLT (N=348, 75%)
  10. 10. Is Palliative Surgery Justified in the Setting of Stage IV Breast Cancer? Pain Control - Yes Quality of Life - Yes Morbidity and Mortality - ? Survival - ? “Prophylactic” Palliation - ? Cost Effectiveness - ? Physiologic Response - ?
  11. 11. Patients with Stage IV Breast Cancer and Asymptomatic Intact Primary Site
  12. 12. Do Patients with Stage IV Breast Cancer Live Longer with Their Disease? *Chia et al, Cancer 2007 Kaplan-Meier Overall Survival Curves•British Columbia Registry* •N=2150 patients with stage IV breast cancer •Diagnosis years – 1991-2001
  13. 13. Systemic Therapy Utilization Chia et al, Cancer 2007
  14. 14. Cox Regression Analysis for Survival in Stage IV Breast Cancer Chia et al, Cancer 2007
  15. 15. Improved Disease Specific Survival SEER, 1973-2010* *Park et al, JCO 2015 A <3 years from diagnosis B >5 years from diagnosis
  16. 16. Does Surgery in Stage IV Breast Cancer Improve Survival? Meta-analysis of Retrospective Data* Overall Mortality – Surgery vs. No Surgery *Headon et al, Molecular and Clinical Oncology, 2016
  17. 17. How can Surgery Impact Survival in Stage IV Breast Cancer: “Theories” Control of seeding from primary tumor site1 Decrease in formation of tumor stem cells within the primary tumor stroma2 Decrease in tumor- induced immunosuppression by the intact primary site3, 4 1Norton, Massague, Nat Med 2006 2Kamoub et al, Nature 2007 3Campbell et al, Breast Cancer Res Treat 2005 4Danna et al, Cancer Res 2004
  18. 18. *King et al, ASCO 2016 A Prospective Analysis of Surgery and Survival in Stage IV Breast Cancer (TBCRC 013)* Cohort A (N=112) Median Age 51 years (21-77) Median Follow-up 54 months (34-78) Median Tumor Size 3.2 cm (0.8-15 cm) ER+/HER2- 71 (63%) ER+/HER2+ 24 (21%) ER-/HER2+ 9 (8%) ER-/HER2- 8 (7%) Responders 94 (85%) 3 year OS 70% (95% CI, 63-79%)
  19. 19. *King et al, ASCO 2016 A Prospective Analysis of Surgery and Survival in Stage IV Breast Cancer (TBCRC 013)* Responders (N=94) Surgery (N=39, 41%) No Surgery (n=55, 59%) P Median Tumor Size 3.8 cm 3.2 cm 0.01 Single Metastatic Site 77% 41% 0.001 1st Line Chemotherapy 39% 17% 0.002
  20. 20. *King et al, ASCO 2016 A Prospective Analysis of Surgery and Survival in Stage IV Breast Cancer (TBCRC 013)* Responders Surgery N Median Survival, mos (95%CI) 3yr OS (95%CI) P Overall N 51 71 (56-NR) 76 (66-89) 0.85 Y 39 77 (52-NR) 77 (65-91) ER positive N 46 71 (56-NR) 78 (67-91) 0.47 Y 34 77 (53-NR) 79 (67-94) HER2 positive N 12 NR (NR-NR) 83 (65-100) 0.39 Y 15 77 (77-NR) 100 (100-100)
  21. 21. TBCRC 013 Prognostic Impact of 21-Gene Recurrence Score in Patients With Stage IV Breast Cancer* *King et al, JCO 2016 •Prospective registry to evaluate approach to local therapy for stage IV breast cancer (N=127) •Cohort A – Patients diagnosed with de novo metastatic disease (N=112) •Cohort B – Patients found to have distant metastases within 3 months of breast cancer diagnosis (N=15) •Median patient age - 52 years •Median follow-up – 29 months
  22. 22. TBCRC 013 Clinical Characteristics and the 21-Gene Recurrence Score in Patients With Stage IV Breast Cancer* *King et al, JCO 2016
  23. 23. TBCRC 013 21-Gene RS vs. Time to First Progression and 2 Year Overall Survival* *King et al, JCO 2016
  24. 24. TBCRC 013 Median Time to Progression and 2 Year Overall Survival in Patients with De Novo Stage IV Breast Cancer* *King et al, JCO 2016
  25. 25. Prospective Randomized Trials Country Accrual Period N Initial Therapy Radiotherapy Status India 2005-2012 350 Chemotherapy If indicated Closed, mature follow-up Japan 2011-2016 410 Systemic therapy Not addressed Enrolling USA, Canada 2011-2015 368 Systemic therapy As for stage I-III disease Closed, July 2015 Turkey 2008-2012 271 Surgery For breast conservation Closed, mature follow-up Netherlands 2011-2016 516 Surgery For positive margins and palliation Closed due to lack of accrual Austria 2010-2019 254 Surgery As for stage I-III disease Closed, now allows pre- operative systemic therapy
  26. 26. Locoregional Treatment versus No Treatment of the Primary Tumour in Metastatic Breast Cancer: an Open-Label Randomized Controlled Trial* *Badwe et al, Lancet Oncology 2015 •350 patients with de novo stage IV breast cancer (February 2005 – January 2013) who had an objective response to 6 cycles of anthracycline-based chemotherapy •Randomization •Loco-regional treatment (LRT) (N=173) •No LRT (N=177) •LRT – Surgery (breast conservation or mastectomy , plus ALND), followed by radiation therapy, “as per standard adjuvant guidelines” •Stratification (balanced by all criteria) •ER Status •Number of metastatic lesions (<3 vs. >3) •Metastatic sites: •Bone •Visceral •Both •Median Follow-up – 17 months •Total deaths N=218 (LRT – N=111 (64%), no LRT – N=107 (60%))
  27. 27. Locoregional Treatment versus No Treatment of the Primary Tumour in Metastatic Breast Cancer: an Open-Label Randomized Controlled Trial* *Badwe et al, Lancet Oncology 2015 LRT (N=173) No LRT (N=177) Hazard Ratio P Median OS (months) 18.8 20.5 1.07 (95% CI 0.82-1.4) 0.6 2 year OS 40.8% 43.3% 1.00 (95% CI 0.76-1.33) 0.98 Problem – lack of HER2 directed therapy
  28. 28. Locoregional Treatment versus No Treatment of the Primary Tumour in Metastatic Breast Cancer: an Open-Label Randomized Controlled Trial* *Badwe et al, Lancet Oncology 2015 Locoregional Progression
  29. 29. Locoregional Treatment versus No Treatment of the Primary Tumour in Metastatic Breast Cancer: an Open-Label Randomized Controlled Trial* *Badwe et al, Lancet Oncology 2015 Distant Progression
  30. 30. A Randomized Controlled Trial Evaluating Resection of the Primary Breast Tumor in Women Presenting with De Novo Stage IV Breast Cancer: Turkish Study (Protocol MF07-01)* *Soran et al, ASCO 2016 •274 patients with de novo stage IV breast cancer • Randomization •Loco-regional surgery (LRS) group (N=138) •Systemic therapy (ST) only group (N=136) •Balanced for age, BMI, HER2 status, tumor histology, tumor size, tumor grade, bone and visceral metastases •Median follow-up – 40 months •Total deaths – N=187 (LRS – N=76 (55%), ST – N=101 (74%)) •36-month survival – no difference (60% for LRS, 51% for ST, p=0.5) •Median OS - 34 months longer with LRS than with ST
  31. 31. Median Overall Survival Turkish Study (Protocol MF07-01)* *Soran et al, ASCO 2016 Hazard Ratio P LRS vs. ST 0.66 (95% CI 0.49-0.88) 0.005 ER+/PR+ vs. not 0.64 (95% CI 0.46-0.91) 0.01 HER2 negative vs. not 0.64 (95% CI 0.45-0.91) 0.01 Age <55 years 0.57 (95% CI 0.38-0.86) 0.006 Solitary bone metastasis only 0.47 (95% CI 0.23-0.98) 0.04
  32. 32. Is Definitive Local Therapy Justified in the Asymptomatic Stage IV Breast Cancer Patient? •Possibly for those with a dramatic and durable response to systemic therapy - more data are needed •Systemic therapy and advances in the development of future targeted therapies remain a top priority for these patients

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