1. Definitive Analysis of the Primary Outcomes
ASCO Abstract LBA505
NSABP PROTOCOL B-32
A Randomized, Phase III Clinical Trial to Compare Sentinel Node Resection to Axillary Dissection in Clinically Node-Negative Breast Cancer Patients
Definitive Analysis of the Primary Outcomes
DN Krag, SJ Anderson, TB Julian, A Brown, SP Harlow, JP Costantino, T Ashikaga, D Weaver, EP Mamounas, N Wolmark

2. All trials reported higher survival in the AD group
AD vs. no AD
Randomized Trials
Survival
All trials reported higher survival in the AD group
Orr RK. Ann Surg Oncol 1999;6(1):109-16

3. Few vs. Some vs. Many Survival >15 nodes 1-5 nodes
All nodes negative
Nodes Examined
1-5
6-10
11-15
16+ 
Krag et al. Ann Surg Oncol, (10): p. 1-8.

4. Anatomy

5. Clinically Negative Axillary Nodes Intraop cytology & postop HE*
07/16/96
B-32
Stratification
Age
Clinical Tumor Size
Type of Surgery
Clinically Negative Axillary Nodes
Randomization
GROUP 1
SN +AD
GROUP 2 SN
Intraop cytology & postop HE
SN Neg
(SN+AD)
SN Neg
(SN only)
SN Pos
SN pos
+ AD FU FU
1,975 patients
2,011 patients * ##

6. SN Detection Methods Technetium sulfur colloid Blue dye
B-32 Surgery
Technetium sulfur
colloid
Blue dye
Palpation (~2% cases)

7. Standardized Path Protocol
B-32 Pathology
Standardized Path Protocol
Intraop- Cytology
Postop- HE

8. Core Trainers Travel Map
B-32 Training
Seth Harlow
Thomas Julian
David Krag
Fred Moffat
Roberto Kusminsky
Sheldon Feldman
Suzanne Klimberg
Peter Beitsch
R. Dirk Noyes

9. Surgeon Performance 224 surgeons audited 94 items per case
B-32 QC
SN Surgery is complex - expect variation
Surgeon Performance
224 surgeons audited
94 items per case
averaged below one error per patient.
Sets a standard for surgical trials
Supports accuracy and conclusions of the B-32 trial.

10. B-32 Analysis Plan 3,989 - SN neg (71% of 5611)
99.9% - follow-up information
95 months - average time on study
Primary endpoints OS, DFS, Regional Control
Study powered to detect 2% difference OS

11. Evenly Balanced Entry Characteristics Associated Treatments Age Race
Tumor size
Surgical treatment plan
Associated Treatments
Radiation Therapy 85% & 84%
Systemic Therapy 82%

12. B-32 OS
NSABP Protocol B-32
Overall Survival for Sentinel Node Negative Patients
100 80 60
% Surviving 40
Trt N Deaths
SNR+AD
SNR HR=1.20 p=0.117 20
Data as of December 31, 2009 2 4 6 8
Years After Entry
* 300 deaths triggered the definitive analysis
* 309 reported as of 12/31/2009 12

13. Protocol B-32: Sentinel Negative Patients
B-32 OS
Protocol B-32: Sentinel Negative Patients
Smoothed Hazard Ratio Plots for Mortality
10.0
5.0
2.0 HR
1.0
0.5
0.2
Data as of December 31, 2009
0.1 2 4 6 8
Time after Randomization (Year) 13

14. B-32 SN Negative Patients: Hazard Ratios of OS
B-32 OS
B-32 SN Negative Patients: Hazard Ratios of OS
According to Stratification Variables
Planned Mastectomy
Planned Lumpectomy
Tumor size >2 cm
Tumor size ≤ 2 cm
Patients 50 + at entry
Patients < 50 at entry
All patients with follow-up
HR= 1.2
SNR better
SNR+AD better
0.2
0.6
1.0
1.4
1.8
2.2
2.6
Hazard Ratio

15. B-32 DFS
NSABP Protocol B-32
Disease-Free Survival for Sentinel Node Negative Patients
100 80 60
% Disease-Free 40
Trt N Deaths
SNR+AD
SNR HR=1.05 p=0.542 20
Data as of December 31, 2009 2 4 6 8
Years After Entry

16. B-32 SN Negative Patients: Hazard Ratios of DFS
B-32 DFS
B-32 SN Negative Patients: Hazard Ratios of DFS
According to Stratification Variables
Planned Mastectomy
Planned Lumpectomy
Tumor size >2 cm
Tumor size ≤ 2 cm
Patients 50 + at entry
Patients < 50 at entry
All patients with follow-up
HR= 1.05
SNR better
SNR+AD better
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
Hazard Ratio

17. B-32 Hazard Ratios Between Groups
B-32 DFS
B-32 Hazard Ratios Between Groups
According to Site of Treatment Failure
Dead, NED
2nd cancers
Opposite Breast Cancers
Distant Recurrences
Local Regional Recurrences
All events
HR= 1.05
SNR better
SNR+AD better
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
Hazard Ratio

18. Local and Regional Recurrences
B-32 RR
Local and Regional Recurrences
as First Events
Group 1
Group 2
Local
54 (2.7%)
49 (2.4%)
Axillary
2 (0.1%)
8 (0.3%)
Extra-axillary
5 (0.25%
6 (0.3%)

19. Residual Morbidity at End of Follow-up
B-32 Morbidity
Residual Morbidity at End of Follow-up
Lower in SN group
Not nonexistent
Group 1
SN + AD
Group 2 SN
Shoulder abduction deficit
19%
13%
Arm volume difference >5%
28%
17%
Arm numbness
31% 8%
Arm tingling 7%
Ashikaga et al JSO in press
All differences p<0.001

20. Quality of Life Sub-Study
789 SN-negative patients
Questionnaires: Weeks 1 & 2-3. q6 months through 3 years.
AD > SN
Ipsilateral arm and breast symptoms p≤0.002 all
Restricted work and social activity
Impaired QOL
From 1 – 3 years
<15% of either group reported moderate or greater severity
Arm morbidity was greater with AD than SN, but lower than expected even for AD.
Land et al, JCO, in press

21. NSABP B-32 Conclusion No significant differences were observed
OS, DFS, or Regional Control
Morbidity decreased
When the SN is negative, SN surgery alone
with no further AD is appropriate, safe, and
effective therapy for breast cancer patients
with clinically negative lymph nodes.