SEER Staging Trends Gold Standard, before sentinel...
Transcript of SEER Staging Trends Gold Standard, before sentinel...
Sentinel Lymph Nodes in Breast Cancer:
Histology, reporting, andclinical implications!"#$%&'(&)"*+,
Sentinel Lymph Nodes in Breast Cancer:
Histology, reporting, andclinical implications!"#$%&'(&)"*+,
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Sentinel Lymph Node
First node in regional nodal basin that drains a primary tumor and reflects the tumor status of the entire nodal basin
Surgical aspects per Dr. Morrow
Gold Standard, before sentinel methodology accepted
• Axillary lymph node dissection (although minimal cases missed)
• Histopathologic study of nodes
• report # of positive nodes/ # nodes
present
Sentinel Lymph Node
• Gross examination
• Frozen section
• Touch prep
• Immunohistochemistry
• PCR[not indicated, high false +]
SEER Staging Trends (1983-1998)
• Stage 0 – increase
• Stage 1 - increase
• Stage 2 node negative – stable
• Stage 3, 4 – stable
• Stage 2, node positive - increase of as much as 30%,most minimal involvement
Metastasis in SLN
SLND ALND
no. patients 162 134
% positive 42% 29%
% <2mm) 38% 10%
Giuliano, Ann Surg 1995
Outcome and Node AnalysisEarly,1999,espouse conservative
“IHC metastases do not appear to adversely affect prognosis”
“IHC should not be routinely performed” on SLN, “nor should treatment decisions be made”[recall that average size is T1c, and grades
are mostly low.]
Turner, et al., Am J Surg Pathol, 23: 263-7, 1999
CO$T CON$IDERATIONDon Weaver,MD
• In order to detect single cells:– Section at 10 micron (0.01 mm) intervals
– One paraffin block (2 mm) results in 200 slides
• $12 per slide = $4800 per case
• Newly diagnosed breast cancer in US = $900 million annually
• 77 million slides
Significance of isolated tumor cells and
Cell Clusters (ITCs)
?X
xx
xx
x
xxxx
xxxxxxx
Xx
xx
xx
xxxx
xxxxxxx
Patterns: missed & detected micrometastasesPatterns: missed & detected Patterns: missed & detected micrometastasesmicrometastases
Xx
xx
xx
xxxx
xxxxxxx
Xx
xx
xx
xxxx
xxxxxxx
pN0(i+)
pN1mi
pN0(i-)
pN0(i-)
Don Weaver
Patterns of missed micrometastases for various strategies
Three levels
200 micron intervals
Two levels
1.0 mm interval
Four levels through block
500 micron (0.5 mm) intervals
Multiple levels through block
200 micron intervals
Don WeaverPathologistsPathologists’’ chargecharge
Minimal epithelial cells need to be examined and analyzed without
the assumption that they represent relevant node involvement by
cancerQuantitatively and Qualitatively
False Positive Nodal Involvement
CK staining of dendritic macrophages, and
plasmablasts as well as degenerating cell debris
Benign inclusions
Viable fragments of papillomas
Benign transport: usually fragments of hyperplasia
as seen in the displaced clusters in granulation
tissue of biopsy site
or papilloma(s)
Artifactual keratinocytes in plane above node
Benign Transport
• 15 cases from breast consult files
• Node dissection 15 days after biopsy
• 7 of 15 with DCIS
• Cluster (<100!m) of epithelial cells in subcapsular sinus accompanied by hemosiderin-laden macrophages, giant cells, and altered RBC’s
Carter et al, Am J Clin Pathol, 2000
Nl. Glands at Bx. SiteCLUSTER OF 3 DEGENERATING CELLS IN SINUS
WITH SURROUNDING MACROPHAGE REAXN.
AJCC Cancer Staging2002
• Micromets distinguished from ITC
• Identifiers added to indicate SLN and IHC
• Major classification of lymph node status designated according to number of involved axillary nodes
AJCC/UICC Cancer Staging
6th edition
Isolated tumor cells (ITCs)
defined as single tumor cells or small clusters not greater than 0.2 mm
pN0 (it)
Modified by Singletary,et al,
Cancer; 2003
ITC = Isolated tumor cells and cell clustersAJCC Cancer Staging
2003
• Micrometastasis (greater than 0.2 mm, none greater than 2.0 mm)
pN1mi
Dense small cell groups, probably significant
= < 2mm.
Individual Tumor Cells and Clusters, = ITC
Some more “real” than others. Still small
Individual Tumor Cells and Clusters, = ITCIndividual Tumor Cells and Clusters, = ITC
Some more Some more ““realreal”” than others. Still smallthan others. Still small
Normal glandular inclusions in capsuleNormal glandular inclusions in capsuleNormal glandular inclusions in capsule Benign Inclusion, in capsule substanceBenign Inclusion, in capsule substanceBenign Inclusion, in capsule substance
Nodal Inclusion, nl. polarized cellsNodal Inclusion, Nodal Inclusion, nlnl. polarized cells. polarized cells ITC or Benign transportITC or Benign transportITC or Benign transport
Lymph Node Sinusoid, Nl. Gland & giant cellLymph Node Sinusoid, Lymph Node Sinusoid, NlNl. Gland & giant cell. Gland & giant cell
CK, B9 transport & CK, B9 transport & squamoussquamous metaplasiametaplasia
Sinusoid
Individual tumor cells and clustersITCITC
Benign Benign papillomapapilloma ““inclusioninclusion”” in nodein node Benign transport, Benign transport, subcapsularsubcapsular sinussinus
AnucleateAnucleate squamessquames in in subcapsularsubcapsular sinussinus
Occult Cells in Lymph Nodes
Does the finding change the prognosis from that already indicated by other information?
Implication of minimal cells in other nodesother nodes not = survival survival predictionprediction
But may indicate other nodes But may indicate other nodes with tumorwith tumor
Viale et al, Ann. Surg;2005
further axillary involvement was significantly
associated with the type and size of SLN metastases, the number of affected SLNs, and the occurrence of peritumoral vascular invasion. A predictive model was able to identify subgroups of patients at significantly different risk for further axillary involvement. CONCLUSIONS: Patients with the most favorable combination of predictive factors still have no less than 13% risk for nonsentinel lymph node metastases and should be offered completion ALND outside of clinical trials of SLN biopsy without back-up axillary dissection.
further further axillaryaxillary involvement was significantlyinvolvement was significantly
associated with the type and size of SLN associated with the type and size of SLN metastases, the number of affected metastases, the number of affected SLNsSLNs, and , and the occurrence of the occurrence of peritumoralperitumoral vascular vascular invasion. A predictive model was able to invasion. A predictive model was able to identify subgroups of patients at identify subgroups of patients at significantly different risk for further significantly different risk for further axillaryaxillary involvement. CONCLUSIONS: Patients involvement. CONCLUSIONS: Patients with the most favorable combination of with the most favorable combination of predictive factors still have no less than predictive factors still have no less than 13% risk for 13% risk for nonsentinelnonsentinel lymph node lymph node metastases and should be offered completion metastases and should be offered completion ALND outside of clinical trials of SLN biopsy ALND outside of clinical trials of SLN biopsy without backwithout back--upup axillaryaxillary dissection.dissection.
Pinder et al, Br.J.Cancer;2005• Metastatic deposits were classified as macrometastasis (>2.0
mm), micrometastasis (0.2-2.0 mm) or isolated tumour cells (ITC, <0.2 mm). Of the 216 patients, 56 (26%) had metastasis as identified by H&E. IHC detected metastatic deposits in a further nine patients (4%), of whom four (2%) had micrometastasis and five (2%) had ITC only. Those with micrometastases were all, on review, visible on the H&E sections. IHC detects few SLNs, of which were either micrometastasis or ITC. Until the prognostic significance of these deposits has been determined, IHC may be of limited value in the histopathological examination of SLNs
The Milan Studies involve complete analysis of each node
There are varieties of epithelial presence
other than benign transport in lymph nodes
There are also instances of cytokeration staining of
other than epithelial cells, particularly of
dendritic macrophages
Micrometastasis <2 mm
Recorded: N1
Prognostically: N0
AJCC Staging Manual 5th edition
Minimal Occult Metastasis
author method survival impact
De Mascarel IHC none
Cote IHC none overall, postmenopausal only
References for D.Page- Pathology of Sentinel Lymph Nodes in Breast Cancer. Feb. 2006. AJCC reporting and CAP Guidelines: 7,9,13,14
Pathology and prediction10-12
1-6,8,15-24
1. Carter BA, Jensen RA, Simpson JF, et al.: Benign transport of breast
epithelium into axillary lymph nodes after biopsy. Am J Clin Pathol 2000, 113:259-65
2. Chagpar A, Middleton LP, Sahin AA, et al.: Clinical outcome of patients with lymph node-negative breast carcinoma who have sentinel lymph node micrometastases detected by immunohistochemistry. Cancer 2005, 103:1581-6
3. Cibull ML: Handling sentinel lymph node biopsy specimens.A work in progress. Arch Pathol Lab Med 1999, 123:620-1
4. de Mascarel I, Bonichon F, Coindre JM, et al.: Prognostic significance of breast cancer axillary lymph node micrometastases assessed by two special techniques: reevaluation with longer follow-up. Br J Cancer 1992, 66:523-7
5. de Mascarel I, MacGrogan G: [Strategies for management of axillary lymph nodes in breast cancer. Point of view of the Institut Bergonie.]. Ann Pathol 2003, 23:518-33
6. Diaz LK, Hunt K, Ames F, et al.: Histologic localization of sentinel lymph node metastases in breast cancer. Am J Surg Pathol 2003, 27:385-9
7. Fitzgibbons PL, Page DL, Weaver D, et al.: Prognostic factors in breast cancer. College of American Pathologists Consensus Statement 1999. Arch Pathol Lab Med 2000, 124:966-78
8. Goyal A, Douglas-Jones A, Newcombe RG, et al.: Predictors of non-sentinel lymph node metastasis in breast cancer patients. Eur J Cancer 2004, 40:1731-7
9. Greene FL, Page DL, Fleming ID, et al. (editors): AJCC Staging Manual. New York, Springer-Verlag, 2002
10. Intra M, Zurrida S, Maffini F, et al.: Sentinel lymph node metastasis in microinvasive breast cancer. Ann Surg Oncol 2003, 10:1160-5
11. Klevesath MB, Bobrow LG, Pinder SE, et al.: The value of immunohistochemistry in sentinel lymph node histopathology in breast cancer. Br J Cancer 2005, 92:2201-5
12. Koscielny S, Le MG, Tubiana M: The natural history of human breast cancer. The relationship between involvement of axillary lymph nodes and the initiation of distant metastases. Br J Cancer 1989, 59:775-82
13. Singletary SE, Greene FL: Revision of breast cancer staging: the 6th edition of the TNM Classification. Semin Surg Oncol 2003, 21:53-9
14. Singletary SE, Greene FL, Sobin LH: Classification of isolated tumor cells: clarification of the 6th edition of the American Joint Committee on Cancer Staging Manual. Cancer 2003, 98:2740-1
15. Trojani M, de Mascarel I, Bonichon F, et al.: Micrometastases to axillary lymph nodes from carcinoma of breast: detection by immunohistochemistry and prognostic significance. Br J Cancer 1987, 55:303-6
16. Trojani M, de Mascarel I, Coindre JM, et al.: Micrometastases to axillary lymph nodes from invasive lobular carcinoma of breast: detection by immunohistochemistry and prognostic significance. Br J Cancer 1987, 56:838-9
17. Veronesi U, Galimberti V, Mariani L, et al.: Sentinel node biopsy in breast cancer: early results in 953 patients with negative sentinel node biopsy and no axillary dissection. Eur J Cancer 2005, 41:231-7
18. Veronesi U, Paganelli G, Viale G, et al.: A randomized comparison of sentinel-node biopsy with routine axillary dissection in breast cancer. N Engl J Med 2003, 349:546-53
19. Viale G, Maiorano E, Pruneri G, et al.: Predicting the risk for additional axillary metastases in patients with breast carcinoma and positive sentinel lymph node biopsy. Ann Surg 2005, 241:319-25
20. Viale G, Sonzogni A, Pruneri G, et al.: Histopathologic examination of axillary sentinel lymph nodes in breast carcinoma patients. J Surg Oncol 2004, 85:123-8
21. Viale G, Zurrida S, Maiorano E, et al.: Predicting the status of axillary sentinel lymph nodes in 4351 patients with invasive breast carcinoma treated in a single institution. Cancer 2005, 103:492-500
22. Weaver DL: Sentinel lymph node biopsy in breast cancer: creating controversy and defining new standards. Adv Anat Pathol 2001, 8:65-73
23. Weaver DL: Occult "micrometastases" in ductal carcinoma in situ: investigative implications for sentinel lymph node biopsy. Cancer 2003, 98:2083-7
24. Weaver DL: Sentinel lymph nodes and breast carcinoma: which micrometastases are clinically significant? Am J Surg Pathol 2003, 27:842-5
Monica Morrow, M.D.Monica Morrow, M.D.
Chairman, Department of Chairman, Department of
Surgical OncologySurgical Oncology
G. Willing Pepper Chair in Cancer ResearchG. Willing Pepper Chair in Cancer Research
Sentinel Node Biopsy and Clinical
Decision Making
The Evolving Role of Axillary Dissection
Therapy
Prognosis
Need for Adjuvant Rx
Local Control
1900’s 1970’s 1980’s 1990’s
Re-Examining Axillary Dissection
• Increased frequency of small
mammographically detected tumors
• Systemic therapy of N+ and N0
Cancers
• Neoadjuvant Chemotherapy
AuthorAuthor nn % SN identified% SN identified % False negative% False negative
GiulianoGiuliano 107107 9494 00
BorgsteinBorgstein 130130 9494 22
VeronesiVeronesi 376376 9999 6.76.7
DeCiccoDeCicco 250250 9696 2.52.5
ZervosZervos 149149 8989 44
CoxCox 186186 9393 0.80.8
Results of SN Biopsy: Single Institution TrialsResults of SN Biopsy: Single Institution Trials Is SN Biopsy the Standard of Care?Is SN Biopsy the Standard of Care?
• Can the results of single institution studies be generalized?
• What is an acceptable false negative rate?
• Long-term outcomesLocal controlMorbidity
NSABP B32NSABP B32
Clinical NO
SN Biopsy + Axillary Dissection
SN Biopsy
RANDOMIZE
SN- SN+
No Further
SurgeryAxillary
Dissection
ACOSOG Sentinel Node Study
T1 -T2
Candidate for BCT
SN Biopsy
N+ N -
Axillary No Axillary
Dissection DissectionRT to Breast IHC
+ Adjuvant Rx SN
+
Marrow
RT to Breast
Adjuvant Rx
ACOSOG Z10ACOSOG Z10 NSABP B32NSABP B32
# Cases# Cases 53275327 52105210
# Surgeons# Surgeons 198 198 233233
TechniqueTechnique AnyAny combinedcombined
TrainingTraining 2020--30 cases +ALND Proctor, 5 cases + ALND30 cases +ALND Proctor, 5 cases + ALND
PatientsPatients TT11 TT22, N, N00 + BCT+ BCT TT11 TT22 NN00, any surgery, any surgery
Comparison of NSABP B32 and Comparison of NSABP B32 and
ACOSOG Z10ACOSOG Z10Comparison of NSABP B32 and Comparison of NSABP B32 and
ACOSOG Z10ACOSOG Z10
ACOSOG Z10 NSABP B32
SN ID 98.6% 97%
SN positive 24% 26%
BMI p BMI p !! 0.0001 0.0001
Age p Age p !! 0.00010.0001
Cases accrued p Cases accrued p !! 0.00010.0001
Not SignificantNot Significant
Nodal statusNodal status
T sizeT size
Tumor locationTumor location
HistologyHistology
Biopsy TypeBiopsy Type
Factors Associated with SN Factors Associated with SN
IdentificationIdentificationResults of SN Biopsy: Collaborative StudiesResults of SN Biopsy: Collaborative Studies
No. of Technique (%) SN False -
Author Patients Localization Identification Rate(%)
Krag 443 R 91 11
McMasters 806 Any 88 7.2
Shivers 560 B&R 85 4.0
Tafra 535 B&R 87 13
Bergkvist 498 B&R 90 11
NSABP 5210 B&R 97 9.7
R - radioactivity
B - blue dye
SN Biopsy Reliably Stages the SN Biopsy Reliably Stages the AxillaAxilla
SN BiopsySN Biopsy
ManselMansel
N = 1031N = 103124.8%24.8%
% Nodal Metastases
VeronesiVeronesi
N = 516N = 51635.5%35.5%
AxillaryAxillary DissectionDissection
23.8%23.8%
32.3%32.3%
Local Control After SN Biopsy AloneLocal Control After SN Biopsy Alone
Author n
no. AxillaryFailures
RoumenShiversDessureaultChungHansenLozaBadgwellVeronesiCody
100309890206238168159259
2,222
000101003
Mean Follow-up(months)
2416202639213246*31*
* median
Total 4,551 5 (0.001%)
Initial Results: ACOSOG Z10Initial Results: ACOSOG Z10n=5327n=5327
•• 16 16 axillaryaxillary LRsLRs (0.3%) at a median of (0.3%) at a median of 31 mo follow31 mo follow--upup
•• 3/16 1+SN, no ALND3/16 1+SN, no ALND1/16 3+ SN, ALND done1/16 3+ SN, ALND done12/16 SN negative, no ALND12/16 SN negative, no ALND
•• Median to recurrence 16 mo Median to recurrence 16 mo (4.2 (4.2 –– 40.1 mo)40.1 mo)
Is SN Biopsy the standard of care?Is SN Biopsy the standard of care?
•• SN biopsy reliably identifies SN biopsy reliably identifies axillaryaxillarynodal metastases with low morbidity.nodal metastases with low morbidity.
•• Long term local control rates after SN Long term local control rates after SN biopsy are excellent.biopsy are excellent.
•• SN biopsy is the procedure of choice for SN biopsy is the procedure of choice for managing the clinically node negative managing the clinically node negative axillaaxilla today.today.
Rationale for Rationale for AxillaryAxillary Surgery in DCISSurgery in DCIS
• Incomplete sampling
• Diagnosis by core bx
• DCIS has the ability tometastasize
How Common is Undiagnosed Invasive Cancer?How Common is Undiagnosed Invasive Cancer?
• Cause specific survival rates of 97% - 100% NOT
compatible with high rates of invasive cancer
• Smaller mammographic DCIS seen today less
likely to have undiagnosed invasion
• Pathologic sampling more extensive
Author # Patients % Invasive
Kestin 2000 130 7.7
Rosenfeld Darling 2000 289 14
Cox 2001 240 12.5
Cox 2003 499 9.4
Morrow 238 13.3
DCIS Diagnosed by Core Biopsy:
How Common is Sampling Error?
Does DCIS Have The Capacity To
Metastasize?
Pendas Klauber-DeMore
n=87 n=76
SN+ 5 (6%) 9 (12%)
IHC only 3 7
Addl. + nodes 0 1/6
Invasion in primary 1 18 “suspicious”
What do IHC Positive Cells in DCIS Mean?
• Retrospective review
• 79 DCIS patients F/U > 10 years
• Axillary Dissection performed
• Nodes recut, IHC performed
4 IHC positive patients (5.1%)
Outcome: 8/79 patients recurred, NONE with IHC+
Cox, Moffit
When Should Sentinel Node Biopsy
Be Performed in DCIS
• Microinvasive carcinoma
Metastases in 3% - 20% of cases
• DCIS treated by mastectomy
opportunity lost if invasion found
• Done as a second procedure if invasion
found after lumpectomy
Prior biopsy does not interfere with mapping
Contraindications to SN BiopsyContraindications to SN Biopsy
• Locally advanced breast cancer
• Pregnancy and Lactation
• Prior axillary surgery
Is a Repeat SN Biopsy Feasible?Is a Repeat SN Biopsy Feasible?
Intra, et al n=18
100% SN identification
2/18 positive
No axillary recurrence at 12.7 mo median
Ann Surg Oncol 2005
ControversiesControversies
• Multicentricity
• Internal Mammary Nodes
• Neoadjuvant Therapy
SN Biopsy for SN Biopsy for MulticentricMulticentric CancerCancer
• Original hypothesis: Unique drainage pathway for each cancer.
• Concordance studies indicate the majority of breast tumors drain via central collecting system.
• Reasonable to do a subareolar injection or separate peritumoral injections.
SN Biopsy for SN Biopsy for MulticentricMulticentric CancerCancer
Author Number of Cases % SLN identified % Sensitivity
Kumar, et al 10 100 100
Tousimis, et al 70 96 92
Kumar, et al 59 93 100
Ozmen, et al 21 86 89
Fernandez, et al 53 98 100
Jin Kim, et al 5 100 100
Schrenk, et al 19 100 100
Total 237 95.4 96.9
Internal Mammary Node Metastases
7070 Patients
22.4% I.M. node positive
4.9% I.M. node were only site
of metastases
Morrow and Foster, Arch Surg 1981
How Common are Isolated IM How Common are Isolated IM
Metastases?Metastases?
• Dupont, et al Vander Ent, et al ALMANAC
3/1273 3/256 5/1139
0.2% 1.2% 0.4%
Nodal Response to Neoadjuvant Therapy?
Tumor SN
Non-SN
SN Biopsy After SN Biopsy After NeoadjuvantNeoadjuvant RXRX
Studies Since 2002Studies Since 2002% SN % False
Author n Identified NegativeStearns 2002 34 85 14Brady 2002 14 93 0Miller 2002 35 86 0Reitsamer 2003 30 87 7Balch 2003 32 97 5Vigario 2003 37 94 39Piato 2003 42 98 17Schwartz 2003 21 100 9Kang 2004 80 76 7Patel 2004 42 95 0Shimazu 2004 47 94 12
SN Biopsy After SN Biopsy After NeoadjuvantNeoadjuvant RXRX
HIGHLY VARIABLE RESULTS DUE TO:
– SMALL NUMBERS 2/17 STUDIES > 50 PTS
– DIVERSE POPULATIONS
T1 – T4
N0, N+
– ? CLASSIFICATION PALPABLE, ABNORMAL
NODES
T1C - T3, N0 or N1
NSABP B27NSABP B27
Randomize
AC x 4
Surgery
Docetaxol x 4
AC x 4
Surgery
AC x 4
Surgery
Docetaxol x 4
Accuracy of SN BiopsyAccuracy of SN Biopsy
NEOADJUVANT RX PRIMARY SURGERY
NSABP B27 Metaanalysis, 2002
69 Studies
n=428/2365 n=10,000
SN identified 85% 90%
False negative 11% 8.4%
Relationship Between SN False Relationship Between SN False
Negative Rate and ResponseNegative Rate and Response
RESPONSE % FALSE NEGATIVE
Clinical
CR 8.7
Other 11.6
p=ns
Accuracy of SN Biopsy by Accuracy of SN Biopsy by
Pathologic ResponsePathologic Response
RESPONSE % ACCURACY
CR 98.4
CCR, Residual tumor 96.0
PR/Stable 94.9
p=ns
Unresolved ProblemsUnresolved Problems
• Is Completion Axillary Dissection
Necessary After a Positive SN
Biopsy?
• Significance of Micrometastases
Management of the Positive SNManagement of the Positive SN
Is Axillary Dissection Indicated?
" Small primary tumors
" Small metastatic deposits not seen intraop
Risk of Additional Metastases: Risk of Additional Metastases:
T1b CancerT1b Cancer
Author n % Cases
Chu - 13
Wong 41 22
Nos 61 12
Viale* 200 34
Van Zee 171 26
*T1a+b
Risk of Additional Metastases by Risk of Additional Metastases by
Size of Size of MetastaticMetastatic DepositDeposit
Author n Size % Cases
Viale 116 <0.2 mm 14.5
212 0.2 – 1 mm 16.9
Leidenius 39 <0.2 mm 20.5
35 0.2 – 1 mm 34.3
Risk of Additional Metastases by Risk of Additional Metastases by
Size/Detection Method: Size/Detection Method:
MicrometastasesMicrometastases
Author n Method % Cases
Mignotte 44 IHC 15.9
24 H&E 33.2
Kamath 26 IHC 7.6
20 H&E 25.0
Multivariate Analyses of Factors Multivariate Analyses of Factors
Predictive of Involvement of Predictive of Involvement of
NonNon--Sentinel NodesSentinel Nodes
n=4017 Patients, 10 Studies
Tumor Size : 5/10 Tumor Grade : 0
Metastases Size: 7/10 # SN involved : 6/9
LVI : 4/10 # SN removed : 3/4
AxillaryAxillary Dissection?Dissection?
Pros:Pros:
• Significant risk of additional nodal disease
• Small survival benefit for dissection cannot be
excluded
• Information on the status of remaining nodes
may help clarify decisions about adjuvant rx
Unresolved QuestionsUnresolved Questions
• Significance of micrometastases
Pathologic Analysis of Lymph NodesPathologic Analysis of Lymph Nodes
• Pre-SLND
– Bivalve lymph nodes
– Half of lymph node discarded
– Section from 1/2 lymph node evaluated with H&E
• Post-SLND
– Serial sections of sentinel node
– Evaluation with H&E and IHC
IHC DetectedIHC Detected MicrometastasisMicrometastasis
Micrometastases
• Present in 7% - 32% H & E negative nodes
• Heterogeneous - ranging from missed tumors greater than 2mm to single cells in subcapsular sinus
• Prognostic significance uncertain
no benefit
important in postmenopausal women
DFS differences 2% - 14%
Significance of Significance of MicrometastasesMicrometastases: :
Ludwig TrialLudwig Trial
• Method: Retrospective analysis of a prospectivetrial
736 of 921 patients included
Serial sections
Single section from first level of node stained for AE-1 and CAM5-2
Median follow-up 12 yrs
Cote, Lancet 1999
Detection of Detection of MicrometastasesMicrometastases::
Ludwig TrialLudwig Trial
H&E
Serial Selection IHC
7% 20%
Cote, Lancet 1999
!""#$%&'()*&'*+,%-.*!""#$%&'()*&/(0-%-.*
12&345
6-0*,0*&78**&9#8.-.,$&:;<
0 2 4 6 8 10 12 14
100
80
60
40
20
0
0 2 4 6 8 10 12 14
Hematoxylin and eosin
12&344=
6-0*,0*&78**&9#8.-.,$&:;<
>-?*&9-'"*&@,')(?-A,%-('&:B*,80<
100
80
60
40
20
0
Prognostic Significance of
MicrometastasesImmunohistochemistry
Cote, Lancet 1999
Time Since Randomization (years)
John Wayne Prospective Study of
Micrometastases
n = 683
• Stage I and II cancer 1/92 - 4/99
• SN Step Sectioned, H & E stained
If H & E – IHC
• Stratified by SN met size
Hansen et al
Results
Group Definition
NegNeg SN (SN (--) H&E & IHC) H&E & IHC
IHCIHC SN (+) IHCSN (+) IHC
MicroMicro SN (+) H&E SN (+) H&E Mets Mets << 2 mm2 mm
MacroMacro
n
419
56
76
132 SN (+) H&E SN (+) H&E Mets > 2 mmMets > 2 mm
Mean Age
5858
5858
5858
56560 20 40 60 80 100
Su
rviv
al (%
)
0
20
40
60
80
100
Disease Free Survival
Time (mos)
IHC 96.67Neg 98.01
Macro 73.56Micro 97.09
5-yr DFS (%)
P=0.0001
Median F/U: 44 mos
IHC Should NOT be used routinely
Decisions regarding Stage and the
need
for adjuvant therapy should be made
on the basis of H & E staining
CAP Consensus
Phila Concensus
ConclusionsConclusions
• SN Biopsy is the procedure of choice for managing the clinically node negative axilla
• Axillary dissection remains standard management for the SN+ patient
• Routine use of IHC awaits results of prospective trials
Sentinel Node Biopsy and Clinical Decision Making
Monica Morrow, M.D.
USCAP, February 12, 2005
References
Kim T, Giuliano AE, Lyman GH. Lymphatic mapping and sentinel lymph node biopsy
in early-stage breast carcinoma. Cancer 2005 [Epub ahead of print]
Lyman GH, Giuliano AE, Somerfield MR, Benson AB 3rd
, Bodurka DC, Burnstein HJ,
Cochran AJ, Cody HS 3rd
, Edge SB, Galper S, Hayman JA, Kim TY, Perkins CL,
Podoloff DA, Sivasubramaniam VH, Turner RR, Wahl R, Weaver DL, Wolff AC, Winer
EP; American Society of Clinical Oncology. American Society of Clinical Oncology
guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer.
J Clin Oncol 2005;23(30):7703-20.
Calhoun KE, Hansen NM, Turner RR, Giuliano AE. Nonsentinel node metastases in
breast cancer patients with isolated tumor cells in the sentinel node: implications for
completion axillary node dissection. Am J Surg 2005;190(4):588-91.
Posther KE. McCall LM, Blumencranz PW, Burak WE Jr, Beitsch PD, Hansen NM,
Morrow M, Wilke LG, Herndon JE 2nd
, Hunt KK, Giuliano AE. Sentinel node skills
verification and surgeon performance: data from a multicenter clinical trial for early-
stage breast cancer. Ann Surg 2005;242(4):593-9.
Mamounas EP, Brown A, Anderson S, Smith R, Julian T, Miller B, Bear HD, Caldwell
CB, Walker AP, Mikkelson WM, Stauffer JS, Robidoux A, Theoret H, Soran A, Fisher
B, Wickerham DL, Wolmark N. Sentinel node biopsy after neoadjuvant chemotherapy in
breast cancer: results from National Surgical Adjuvant Breast and Bowel Project Protocol
B-27. J Clin Oncol 2005;23(21):4808.
Davidson NE, Morrow M, Kopan DB, Koerner FC. A 56-year old woman with breast
cancer and isolated tumor cells in a sentinel node. N Eng J Med 2005;353:67-75.
Cote RJ, Peterson HF, Chaiwun B, Gelber RD, Goldhirsch A, Castiglione-Gertsch M,
Gusterson B, Neville AM, for the International Breast Cancer Study Group. Role of
immunohistochemical detection of lymph-node metastases in management of breast
cancer. The Lancet 1999;354:896-900.