1. Giuliano Pre-SSO mins
ASCO Z mins
ACOSOG Z0011: A Randomized Trial of Axillary Node Dissection in Women with Clinical T1-2 N0 M0 Breast Cancer who have a Positive Sentinel Node
Giuliano AE, McCall L, Beitsch PD, Whitworth PW, Blumencranz PW, Leitch AM, Saha S, Hunt K, Morrow M, Ballman KV 1

2. Sentinel Lymph Node Dissection (SLND) for Breast Cancer
SLND has replaced axillary lymph node dissection (ALND) for histopathologically node-negative women
Numerous studies have demonstrated its staging efficacy and safety
ALND remains the gold standard for node-positive women
ALND more morbidity than SLND

3. Contemporary Breast Cancer
ASCO Z mins
Contemporary Breast Cancer
Tumors are smaller than in past
Fewer node-positive patients
Sentinel node (SN) often only node involved (40-70%)
BCT common – tangential field irradiation treats much of axilla
Adjuvant systemic therapy usually given for node-positive women

4. Modern Randomized Trials of Axillary Treatment with BCT
ALND vs. Obs
Ax RT vs. Obs
ALND vs. Ax RT
Author
Martelli
Veronesi
Louis-Sylvestre N
219
435
658
Median F/U 5
5.3 15
Axillary
Recurrence
0 vs 1.8%
0.5% vs 1.5%
1% vs 3%
No significant differences in survival
Martelli G, Ann Surg 2005, 242:1;
Louis-Sylvestre C, JCO 2004, 22:97;
Veronesi U, Ann Oncol 2005, 16:383.

5. similar locoregional control and survival as
Hypothesis:
SLND alone achieves
similar locoregional control
and survival as
Level I and II ALND for H&E
SN node-positive women.

6. ACOSOG Z0011
A randomized trial of axillary node dissection in women with clinical T1-2 N0 M0 breast cancer who have a positive SN
165 Investigators / 177 Institutions
50 investigators with 5 or more patients
Target accrual 1900 patients (non-inferiority)
Closed early

7. Inclusion/Exclusion Criteria
Eligibility
Clinical T1 T2 N0 breast cancer
H&E-detected metastases in SN (AJCC 5th edition)
Lumpectomy with whole breast irradiation
Adjuvant systemic therapy by choice
Ineligibility
Third field (nodal irradiation) or APBI
Metastases in SN detected by IHC
Matted nodes
3 or more involved SN

8. Z0011 Study Design Schema

9. Study Population Schema 5/99–12/04

10. No meaningful differences in findings.
All analyses performed on both intent-to-treat and actual treatment received.
No meaningful differences in findings.
Intent-to-treat analysis reported.

11. Patient and Tumor Characteristics
ALND
(420 pts)
SLND
(436 pts)
Age (median range)
56 (24-92)
54 (25-90)
Clinical Stage T1 T2
67.9%
70.6%
32.1%
29.4% ER
(+)
(-)
83.0%
83.0%
17.0%
17.0% PR
(+)
(-)
67.7%
69.9.%
32.3%
30.1%
LVI
Yes No
40.6%
35.2%
59.4%
64.8%

12. Patient and Tumor Characteristics
ALND
(420 pts)
SLND
(436 pts)
Modified Bloom-Richardson I
22.0%
25.6% II
48.9%
46.8%
III
29.1%
27.5%
Clinical Tumor
Size (median cm.)
1.7 ( )
1.6 ( )

13. Adjuvant Systemic Therapy
ASCO Z mins
Adjuvant Systemic Therapy
ALND
SLND
Chemotherapy
57.9%
58.0%
Hormonal therapy
46.4%
46.6%
Either/Both
96.0%
97.0%
P = N.S.

14. Median Number of Lymph Nodes Removed

15. Size of SN Metastasis

16. Number of Positive Lymph Nodes

17. had additional positive
106 (27.4%) patients
treated with ALND
had additional positive
nodes removed
beyond SN.

18. Locoregional Recurrences
ALND
(420 pts)
SLND
(436 pts)
Recurrence
Local (Breast)
15 (3.6%)
8 (1.8%)
Regional (Axilla,
Supraclavicular)
2 (0.5%)
4 (0.9%)
Total Locoregional
17 (4.1%)
12 (2.8%)
P = 0.11
Median follow-up = 6.3 years
Regional recurrence seen in only 0.7% of the entire population

19. It is highly improbable that the 0. 9% regional or 2
It is highly improbable that the 0.9% regional or % locoregional recurrence with SLND would significantly impact
survival.

20. Locoregional Recurrence-Free Survival

21. Associations of Prognostic Variables with Locoregional Recurrence
Univariable Analysis
P value
Multivariable Analysis
P value
Treatment Arm NS NS
Age (< 50, > 50)
0.0421
0.0260
ER status
0.0002 NS
PR status
0.0207 NS
# Positive Total LN NS NS
LVI present vs. absent NS NS
Histologic Type NS NS
SN Metastasis Size NS NS
Tumor Size
0.0012 NS
Adjuvant Systemic Therapy NS NS
Modified Bloom-Richardson
0.0002
0.0258

22. ER/PR Status and 5-Year Locoregional Recurrence-Free Survival

23. Disease-Free Survival

24. Associations of Prognostic Variables with Disease-Free Survival
Univariable Analysis
P value
Multivariable Analysis
P value
Treatment Arm NS NS
Age (< 50, > 50) NS NS
ER status
0.0003
0.007
PR status
0.031 NS
# Positive Total LN
0.005 NS
LVI present vs. absent NS NS
Histologic Type NS NS
SN Metastasis Size NS NS
Tumor Size
0.002 NS
Adjuvant Systemic Therapy
0.016
0.006
Modified Bloom Richardson NS NS

25. ER/PR Status and 5-Year Disease-Free Survival

26. Overall Survival

27. Associations of Prognostic Variables with Overall Survival
Univariable Analysis
P value
Multivariable Analysis
P value
Treatment Arm NS NS
Age (< 50, > 50)
0.002
0.006
ER status
0.012
0.013
PR status NS NS
# Positive Total LN
0.044 NS
LVI present vs. absent NS NS
Histologic Type NS NS
SN Metastasis Size NS NS
Tumor Size
0.042 NS
Adjuvant Systemic Therapy
0.020
0.025
Modified Bloom Richardson NS NS

28. ER/PR Status and 5-Year Overall Survival

29. Locoregional Recurrence-Free Survival
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.
Neither number of positive SN, size of SN metastasis, nor number of lymph nodes removed was associated with locoregional recurrence.

30. Disease-Free and Overall Survival
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.

31. alone provided excellent locoregional control and
Conclusion
In this prospective
randomized study SLND
alone provided excellent
locoregional control and
survival comparable to
completion ALND.

32. breast cancer. The role of this operation should be
This study does not
support the routine
use of ALND in early
nodal metastatic
breast cancer. The role of
this operation should be
reconsidered.

33. Acknowledgments The authors thank our courageous patients as well as
the ACOSOG staff and
investigators for their
contributions to this study.