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)