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The Role of SLNB and ALND in
Breast Cancer
Anees B. Chagpar, MD, MSc, MA, MPH
Associate Professor of Surgery, Yale School of Medicine
Director, The Breast Center – Smilow Cancer Hospital at Yale-New Haven
Assistant Director, Yale Cancer Center – Diversity & Health Equity
Program Director, Multidisciplinary Breast Fellowship, Yale University
NSABP B-04
Fisher B, et al. NEJM 2002;347(8):567-575
Lymph Node Evaluation
• Staging
• Local Control
Evolution
1960
1977
1992
1994
Sentinel lymph node biopsy
Study N Accuracy (%) SLN ID (%) FN rate (%)
McMasters (2001) 2206 97 93 8
Tafra (2001) 535 96 87 13
Krag (1998) 443 97 93 11
Veronesi (1999) 376 96 99 7
Haigh (2000) 283 99 81 3
Sentinel Lymph Node Biopsy
Sentinel Lymph Node Biopsy
• Positive:
• Macrometastases > 2mm
• Micrometastases 0.2-2mm
ALND
• Negative:
• Negative
• Isolated tumor cells <0.2 mm
no further axillary surgery
NSABP B-32
• Median f/u:
95.3 mo SLNB
Routine ALND ALND only if
SLN+
1975 SLN-
8 LN recurrences
5-yr OS: 96.4%
2011 SLN-
14 LN recurrences
5-yr OS: 95.0% Krag et al., J Clin Oncol 28:18s, 2010 (abstr LBA505)
Risk of non-SLN disease
Study # patients % with no further
non-SLN metastases
Viale et al. (2005) 794 49.7
Degnim et al. (2005) 574 58.3
Van Zee et al. (2003) 1075 61.1
Schrenk et al. (2005) 379 62.3
Chagpar et al. (2006) 1253 63.1
van Iterson et al. (2003) 135 66.0
Houvenaeghel et al. (2009) 490 84.9
Models to predict non-SLN
metastases
Chen et al., Cancer Sci 2012; 103: 274-281
Revolution
ALND only in SLN+
Predicting non-SLN
No ALND
Clinical Trials
• ACOSOG Z-0011
• IBCSG 23-01
• EORTC AMAROS
SLNB
SLN+
ALND Observation or
XRT
ACOSOG Z-0011
+ SLNB
ALND XRT
• Non-inferiority study;
target accrual 1900
• 27.3% of ALND had
non-SLN metastases
• Median f/u: 6.3 yrs
N=420
# nodes: 17
LN recur: 0.6%
5-yr OS: 91.9%
N=436
# nodes: 2
LN recur: 1.3%
5-yr OS: 92.5% Giuliano et al., Ann Surg 2010; 252:426-433
ACOSOG Z-0011 Trial
• Eligibility:
– Tumors < 5 cm
– 1-2 positive nodes
– No neoadjuvant
therapy
– Partial mastectomy
– Whole breast
radiation therapy
• Study Cohort:
– Tumor size: 1.65 cm
– Median age: 55 yrs
– 28.3% LVI
– 50.2% macromets
– 21.1% grade 3
– 83% ER+
– 96.5% adjuvant
systemic therapy
IBCSG 23-01
+ SLNB
(≤ 2 mm)
ALND No ALND
• Non-inferiority study;
target accrual 1960
• 13% of ALND had non-
SLN metastases
• Median f/u: 5.0 yrs
N=464
# nodes: 21
LN recur: 0.2%
5-yr OS: 97.6%
N=467
# nodes: 2
LN recur: 1.1%
5-yr OS: 97.5% Galimberti et al. Lancet Oncol 2013; 14: 297-305
IBCSG 23-01 Trial
• Eligibility:
– Tumors < 5 cm
– 1 or more positive SLN
– Micrometastases ≤ 2 mm
– No neoadjuvant therapy
• Study Cohort:
– Median age: 54 yrs
– 7% tumors ≥ 3 cm
– 69% SLN deposit ≤ 1 mm
– 90% ER+
– 9% mastectomy
– 3% BCS without XRT
– 96% adjuvant systemic
therapy
Timing of SLNB and NAC
Pre-NAC SLNB Post-NAC SLNB
Identification rate ~100% > 90%
False negative rate < 5-10% Up to 33% (8-13%)
Second surgery Potentially Not necessarily
Ability to avoid ALND Low Higher
Ability to assess pCR May have removed
only positive node
Better able to assess
response
Influences
management
Maybe Maybe
SLNB after NAC
Study N Identification
rate
False negative
rate
Van Deurzen 2148 90.9% 10.5%
Kelly 1799 89.6% 8.4%
Xing 1273 89.7% 12.0%
Hunt 575 97.4% 5.9%*
Mamounas 428 84.8% 10.7%
Classe 195 90.3% 11.5%
San Antonio Breast Cancer Symposium, December 4-8, 2012
Z1071 schema
T0-4, N1-2, M0 invasive breast cancer
(pretreatment axillary ultrasound with FNA or core biopsy
documenting axillary metastases)
Neoadjuvant chemotherapy
↓
SLN and ALND
↓
Node positive disease
637 pts
Chemotherapy
Residual nodal
disease
382 pts (60%)
SLN positive 326 pts
SLN negative /
ALND positive 56 pts (14.7%)
Node negative
255 pts (40%)
ACOSOG Z-1071
• SLN identification rate = 92.5%
• Accuracy = 91.2%
• False negative rate
– Overall: 14.7%
– cN1 disease and 1 SLN: 31.5%
– cN1 disease and 2+ SLNs: 12.8%
• Only 2 SLNs examined: 21.1%
• Dual tracer: 10.8%
Clip
Clip N Residual
disease FNR 95% CI
Placed and
found 96 54 7.4% 2.0 – 17.9%
Placed, but
not found 76 50 14.0% 5.8 – 26.7%
Not placed 353 206 13.6% 9.2 – 19.0%
Role of Ultrasonography
• May provide staging information if done prior
to neoadjuvant chemotherapy without
removing only positive node
• Should we still do SLNB post-NAC in patients
with known axillary disease?
– If so, ultrasound no longer saves patients SLNB
SENTINA Trial 1737 patients
(103 institutions)
cN0 cN1
pN0 pN1
No axillary
surgery
SLNB
Re-SLNB +
ALND
Neoadjuvant Chemotherapy
SLNB +
ALND ALND
Neoadjuvant Chemotherapy
ycN1 ycN0
Arm Identification
Rate FNR
Pre-NAC SLNB 99.1%
Re-SLNB post-NAC 60.8% 51.6%
SLNB post-NAC 80.1% 14.2%
SENTINA Trial
False Negative Rate post-NAC
Lobular vs non-lobulal tumor G3 vs G1-2 Unifocal vs multifocal L0 vs L1 V0 vs V1 Extracaps. extension no vs yes
ER/PgR negative vs positive
HER2-negative vs positive
Large center vs small Number of SLN (1 vs >1)
No pCR vs pCR
OR=.132 (.007, 2.51), p=.178 OR=1.20 (.406, 3.55), p=.741 OR=.961 (.322, 2.86), p=.942
OR=1.66 (.553, 4.99), p=.365
OR=2.33 (.069, 78.5), p=.637
OR=.386 (.103, 1.44), p=.157
OR=1.02 (.321, 3.27), p=.967
OR=1.67 (.496, 5.65), p=.406
OR=.416 (.147, 1.18), p=.098
OR=.505 (.306, .833), p=.008
OR=1.34 (.243, 7.37), p=.737
So….
• Lower identification rate
• Higher false negative rate
• But does it matter?
– NSABP B-04
– ACOSOG Z-0011
Does ALND matter?
• LNR stratifies
prognosis
• ALMANAC and others
→ no change in tx
• No significant change
in local recurrence
Chagpar et al. Ann Surg Oncol 2011; 18(11): 3143-8
Morbidity of Axillary Dissection
Wernicke et al. Am J Clin Oncol 2013; 36(1): 12-19
Future Studies
• Alliance A11202
– Randomize SLN+ patients post-NAC to ALND vs.
axillary RT
• NSABP B-51
– Node positive patients undergoing NAC
→Node negative post-NAC (SLNB and/or ALND)
– Breast radiation if partial mastectomy
– Randomized to regional LN radiation (+ PMRT) vs.
no regional LN radiation (and no PMRT)
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