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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
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• 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
Sentinel Lymph Node Dissection (SLND) for Breast Cancer
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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
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Modern Randomized Trials of Axillary Treatment with BCT
Martelli G, Ann Surg 2005, 242:1; Louis-Sylvestre C, JCO 2004, 22:97; Veronesi U, Ann Oncol 2005, 16:383.
ALND vs. Ax RT
Author
Median F/U
N
Axillary Recurrence
Ax RT vs. ObsALND vs. Obs
Louis-SylvestreVeronesiMartelli
5
219
0 vs 1.8%
5.3
435
0.5% vs 1.5%
15
658
1% vs 3%
No significant differences in survival
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Hypothesis:
SLND alone achieves
similar locoregional control
and survival as
Level I and II ALND for H&E
SN node-positive women.
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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
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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
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Z0011 Study Design Schema
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Study Population Schema 5/99–12/04
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All analyses performed on both intent-to-treat and
actual treatment received.No meaningful differences
in findings. Intent-to-treat analysis
reported.
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Patient and Tumor Characteristics
Age (median range)
Clinical Stage T1T2
ER(+)(-)
LVI YesNo
56 (24-92)
67.9%32.1%
83.0%17.0%
67.7%32.3%
40.6%59.4%
ALND (420 pts)
54 (25-90)
29.4%
17.0%
64.8%
70.6%
83.0%
69.9.%
35.2%
SLND(436 pts)
30.1%
PR(+)(-)
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Patient and Tumor Characteristics
Modified Bloom-Richardson22.0%
48.9%
1.7 (0.4-7.0)
46.8%
25.6%
1.6 (0.0-5.0)Clinical Tumor Size (median cm.)
29.1% 27.5%
I
II
III
ALND (420 pts)
SLND(436 pts)
SLNDSLNDALNDALND
Adjuvant Systemic Therapy
Chemotherapy 57.9% 58.0%
Hormonal therapy 46.4% 46.6%
Either/Both 96.0% 97.0%
P = N.S.
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Median Number of Lymph Nodes Removed
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Size of SN Metastasis
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Number of Positive Lymph Nodes
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106 (27.4%) patients treated with ALND
had additional positive nodes removed
beyond SN.
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Locoregional Recurrences
SLND(436 pts)
ALND (420 pts)
2 (0.5%) 4 (0.9%)Regional (Axilla, Supraclavicular)
15 (3.6%) 8 (1.8%)Local (Breast)
17 (4.1%) 12 (2.8%)Total Locoregional
Recurrence
Median follow-up = 6.3 years
Regional recurrence seen in only 0.7% of the entire population
P = 0.11
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It is highly improbable that the 0.9% regional or 2.8% locoregional recurrence with SLND would significantly impact
survival.
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Locoregional Recurrence-Free Survival
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Associations of Prognostic Variables with Locoregional Recurrence
ER status
PR status
Tumor Size
Histologic Type
0.0002
NS
NS
NS
0.0012
NS
0.0002
0.0421
NS
LVI present vs. absent
SN Metastasis Size
# Positive Total LN
Modified Bloom-Richardson
Treatment Arm
Adjuvant Systemic Therapy
Age (< 50, > 50)
0.0207
NS
NS
NS
NS
NS
NS
NS
0.0258
0.0260
NS
NS
NS
Univariable AnalysisP value
Multivariable AnalysisP value
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ER/PR Status and 5-Year Locoregional Recurrence-Free Survival
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Disease-Free Survival
0
10
20
30
40
50
60
70
80
90
100
0 1 2 3 4 5 6 7 8
Time (Years)
% R
ecu
rren
ce-F
ree
and
Aliv
e
ALND
No ALND
P-value = 0.14
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Associations of Prognostic Variables with Disease-Free Survival
PR status
Tumor Size
Histologic Type
0.031
0.002
0.016Adjuvant Systemic Therapy
NSTreatment Arm NS
0.005# Positive Total LN NS
ER status 0.0003 0.007
NS
Age (< 50, > 50) NS NS
0.006
NS
NS NS
LVI present vs. absent NS NS
Modified Bloom Richardson
Univariable AnalysisP value
Multivariable AnalysisP value
NSNS
NSSN Metastasis Size NS
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ER/PR Status and 5-Year Disease-Free Survival
260
10
20
30
40
50
60
70
80
90
100
0 1 2 3 4 5 6 7 8
Time (Years)
% A
live
ALND
No ALND
P-value = 0.25
Overall Survival
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Associations of Prognostic Variables with Overall Survival
PR status
Tumor Size
Histologic Type
NS
0.042
0.020
Univariable AnalysisP value
Multivariable AnalysisP value
Adjuvant Systemic Therapy
NSTreatment Arm NS
0.044# Positive Total LN NS
ER status 0.012 0.013
NS
Age (< 50, > 50) 0.002 0.006
0.025
NS
NS NS
LVI present vs. absent NS NS
Modified Bloom Richardson NS NS
NSSN Metastasis Size NS
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ER/PR Status and 5-Year Overall Survival
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Summary
• 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.
Locoregional Recurrence-Free Survival
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Summary
• 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.
Disease-Free and Overall Survival
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Conclusion
In this prospective randomized study SLNDalone provided excellentlocoregional control andsurvival comparable to
completion ALND.
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This study does not support the routine use of ALND in early
nodal metastaticbreast cancer. The role of this operation should be
reconsidered.
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Acknowledgments
The authors thank our
courageous patients as well as
the ACOSOG staff and
investigators for their
contributions to this study.