targeting surgery for known axillary...
TRANSCRIPT
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
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.
San Antonio Breast Cancer Symposium, December 4-8, 2012
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
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.
San Antonio Breast Cancer Symposium, December 4-8, 2012
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
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.
San Antonio Breast Cancer Symposium, December 4-8, 2012
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
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.
San Antonio Breast Cancer Symposium, December 4-8, 2012
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
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.
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%
San Antonio Breast Cancer Symposium, December 4-8, 2012
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San Antonio Breast Cancer Symposium, December 4-8, 2012
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 +
San Antonio Breast Cancer Symposium, December 4-8, 2012
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San Antonio Breast Cancer Symposium, December 4-8, 2012
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
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.
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