targeting surgery for known axillary...

Targeting Surgery for

Known Axillary Disease

Abigail Caudle, MD

Henry Kuerer, MD PhD

Dept. Surgical Oncology

MD Anderson Cancer

Center

Nodal Ultrasound at Diagnosis

• Whole breast and draining lymphatic basin

ultrasound performed on all patients with

invasive cancer – Axilla -Internal mammary

– Infra-clavicular -Supraclavicular

• Suspicious lymph nodes biopsied

Fornage

Ultrasound Guided FNA

Krishnamurthy et al Cancer, 2002

Specificity: 100% Positive Predictive Value: 100%

Preoperative Systemic Therapy

• General approach for large primary tumor or

nodal metastases at MDACC

• Response in the breast and nodes can be

monitored during therapy

• Surgery in the axilla following chemotherapy

– Initial node negative: SLN and ALND if positive

– Initial node positive: ALND

Conversion of Axillary Metastases:

Clinically Positive to Pathologic Negative

Clinical Positive NCT

Pathologic Negative

HER2-Negative - 40%

HER2-Positive (with trastuzumab) – 74%

Sentinel Node Biopsy after

Preoperative Chemotherapy for

Node Positive Breast Cancer ?

SLN after Preoperative Chemotherapy for Known Node Positive: Retrospective Studies

Author

Year

Number of

Patients

Identification

Rate (%)

False

Negative Rate

(%)

Mamounas et al. 2005 102 86.3 7.0

Shen et al. 2007 61 91.8 25

Classe et al. 2008 65 81.5 15

Gimbergues et al. 2008 27 - 29.6

Gomez et al. 2008 34 809 15

Chintamani et al. 2011 30 100 13.3

Canavese et al. 2011 64 93.8 5.1

Alvarado et al. 2012 121 93 20.8

San Antonio Breast Cancer Symposium, December 4-8, 2012

This presentation is the intellectual property of the author/presenter. Contact [email protected] for permission to reprint and/or distribute.

The role of sentinel lymph node surgery in patients presenting with node positive breast cancer (T0-T4, N1-2) who receive

neoadjuvant chemotherapy – results from the ACOSOG Z1071 trial

Judy Boughey, Vera Suman, Elizabeth Mittendorf, Gretchen Ahrendt, Lee

Wilke, Bret Taback, Marilyn Leitch, Teresa Flippo-Morton, David Byrd,

David Ollila, Tom Julian, Sarah McLaughlin, Linda McCall, Fraser

Symmans, Carisa Le-Petross, Bruce Haffty, Tom Buchholz, Kelly Hunt

mailto:[email protected]




ACOSOG Z1071

Hypothesis: SLN surgery is an accurate method of axillary staging after NAC in node positive patients

Primary Endpoint: False negative rate of SLN surgery in clinically node positive disease after NAC

ClinicalTrials.gov Identifier: NCT00881361





T0-4, N1-2, M0 invasive breast cancer

(pretreatment axillary ultrasound with FNA or core biopsy documenting

axillary metastases)

↓REGISTER* ↓

Neoadjuvant chemotherapy

↓

REGISTER* ↓

SLN and ALND

Z1071 schema





Methods

Recommended surgical standards

• Resection of minimum of 2 SLNs

• Use of dual tracer (radiocolloid and blue dye)

Pathologic assessment

• Standard processing with H&E staining

• Node positive defined as tumor >0.2mm on H&E





SLN Identification Rate

SLN(s) detected in 639 (92.7%) of 689 women

Patients N SLN

identified

SLN

identification

rate (%)

CI

All patients 689 639 92.7 90.5 - 94.6

cN1 651 605 92.9 90.7 - 94.8

cN2 38 34 89.5 75.2 - 97.1




Node positive disease

637 pts

Node negative

255 pts (40%)

Residual nodal disease

382 pts (60%)

SLN negative / ALND positive

56 pts

SLN positive

326 pts

Chemotherapy

SLN correctly identified nodal status in 91.2%





FNR =

310 patients had residual nodal disease

39 of these patients had negative SLNs

False negative rate among pts with cN1 disease and at least 2 SLNs examined

FNR = 12.6%

95% probability that the FNR lies in the range of 9.4

to 16.7%.

# pts SLN - / ALND +

# pts SLN + or ALND +





Clip placement in patients with cN1 disease and 2+ SLNs examined

172 of 525 (32.8%) patients had clip placed in LN at diagnosis.

Clip N

Nodal

residual

disease

FNR 95% CI

Clip placed and found in

SLN

96 54 7.4% 2.0 - 17.9%

Clip placed, not documented

where located at surgery

76 50 14.0% 5.8 - 26.7%

Clip not placed 353 206 13.6% 9.2 - 19.0%


Nodal FNA and Placement of Gel

Marker

Wei Yang, MD

What is the fate of individual

nodes with documented

metastases?

Question #1:

Prospective Registry of Breast Cancer Patients with

Axillary Nodal Metastases Identified During Ultrasound

Staging at MD Anderson Cancer Center: Protocol 11-1087

• Eligibility: limited axillary disease

– One or two abnormal axillary nodes on US

documented by cytology

• Gel marker clip (visible on ultrasound and

mammography) in node with metastases

• Preoperative chemotherapy

• Routine axillary node dissection

Prospective Registry of Breast Cancer Patients with

Axillary Nodal Metastases Identified During Ultrasound

Staging at MD Anderson Cancer Center: Protocol 11-1087

Routine ALND, identification of marked node, pathologic correlation (disease presence and size) with compared with other nodes

Can we identify the clipped

node intra-operatively?

Question #2:

Feasibility of Selective Image Guided Resection of Cytologically

Documented Axillary Lymph Node Metastases

Following Preoperative Chemotherapy: Protocol 12-0163

T0 – T4

FNA documented axillary

metastases

One or two nodes with clip

placement

Preoperative Chemotherapy

Repeat nodal

ultrasound, FNA

Excision of marked nodes

Routine axillary node dissection

OUTCOME Technical Success? Correlation: FNA results with Histology Clip Node with Others

Potential Next Clinical Protocols?

• Marker placed if <3 suspicious nodes

• Standard chemotherapy

• Assess response by ultrasound

• Biopsy clipped node after NCT-

–Positive ALND

–Negative SLND and removal of clipped

node

• Both negative – no further axillary surgery

• Positive - ALND

Using Biologic Predictors:

NodeS Assay

• Microarray-based genomic predictor

• Based on tumor core or needle biopsies

• Based on two signatures: • Nodal response

• pLN- versus extensive disease

• Pathologic response • pCR/RCB-I vs. RCB-2/RCB-3

Clinically Node Positive

Clinical LN Positive N=88

Predicted Responder N=18

Predicted Non-Responder N=70

pLN Negative N=12

pLN Negative N=27

67% (95% CI 41-87%)

39% (95% CI 27-51%)

Chemotherapy

Symmans et al. ASCO Breast Symposium. Poster Presentation 2009

What about patients who go to

surgery first?

Role of axillary ultrasound in the

post-ACOSOG Z0011 era?

ACOSOG Z0011 Trial

• Designed to determine if ALND impacts survival in selected

SLN positive patients

• Enrolled patients with:

• Clinical T1-2 N0 breast cancer

• Undergoing breast conservation therapy (BCT) followed

by whole breast radiotherapy

• Found to have 1-2 positive SLN

• Randomized patients to ALND versus no ALND

• At median 6.3 follow-up, there was no difference in survival

or locoregional recurrence rates1,2

1 Giuliano et al. JAMA 2011 2 Giuliano et al. Ann Surg 2010

Defining Nodal Disease Burden

• Compared patients T1-2 tumors with axillary

metastasis:

– Cohorts:

• Clinically negative, metastasis found by SLN

• 1-2 suspicious nodes on U/S, confirmed by FNA

– Exclusions:

• >2 suspicious nodes

• N3 disease

• Patients undergoing NCT

• Clinical or pathologic tumor size > 5 cm

Burden of Nodal Disease

Identified by SLN N= 518

Identified by U/S N=149

P value

Mean number of + LN 2.2 3.6 <0.001

Total number of + LN: 1 2 ≥ 3

290 (56%) 127 (25%) 101 (19%)

44 (30%) 38 (25%) 67 (45%)

<0.001

Largest LN Metastasis (Mean)

5.29 mm 13.42 mm <0.0001

Extra-nodal Extension Present

124 (24%) 75 (50%) <0.001

Summary

• Ultrasound with FNA highly sensitive and specific for identification of nodal metastases

• Marking of nodal metastases may allow for targeted excision of disease

– Improve assessment of response?

– Minimize axillary surgery?

• Biologic predictors may also allow targeted surgical therapy



Future Studies

ALLIANCE A11202 Schema

Clinical T1-3 N1 M0 BC

Neoadjuvant Chemotherapy

BCT or Mastectomy

Sentinel Lymph Node Surgery

SLN Negative SLN Positive

Randomization

ALND

Breast/chest wall and nodal

XRT

No further axillary surgery.

Breast/chest wall and nodal

XRT

NSABP B-51/RTOG 1304 (NRG 9353) Schema

Clinical T1-3 N1 M0 BC

Axillary nodal involvement

(FNA or core needle biopsy)

Neoadjuvant chemo (+ Anti-HER-2 therapy for HER-2 neu

pts)

No Regional Nodal XRT

with breast XRT if BCS & No

chest wall XRT if

mastectomy

Regional Nodal XRT

with breast XRT if BCS

and chest wall XRT if

mastectomy

Definitive surgery with histologic documentation of negative

axillary nodes (either by axillary dissection or by SLNB axillary

dissection

Stratification

Type of surgery (mastectomy vs lumpectomy)

ER status (+ vs -), HER-2 status (+ vs -)

pCR in breast (yes vs no)

Randomization


targeting surgery for known axillary...

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