Sentinel Lymph Node Biopsy in Breast Cancer

1
Sentinel Lymph Node Biopsy in Breast Cancer

• Dr Peter Lovrics
• St Josephs Healthcare,
• Department of Surgery, McMaster University
• Hamilton, Ontario

2
Axillary Dissection

• Breast cancer is a common disease.
• Level I II axillary dissection has been the
  standard of care .

3
Why not do ALND?

• Inaccurate predictor of prognosis.
• Primary tumour patient characteristics guide
  adjuvant therapies.
• Radiation therapy delayed ALND provide
  effective local control.
• No impact on survival.
• Morbidity

4
(No Transcript)
5
Why perform ALND?

• Staging ? prognosis
• Staging ? guide chemo radiation therapy
• Longterm regional control
• Minimal morbidity
• Positive impact on survival?

6
Is there a better way?

• Acceptance of BCS minimizing surgical
  morbidity.
• Increased awareness widespread adoption of
  screening ? decreased size of primary earlier
  stage.
• Enhanced, more accurate pathological examination
  of nodal tissue.
• Noninvasive modalities

7
Lymphatic Mapping

• Drainage primarily to the axilla.
• Isolated internal mammary or supraclavicular
  drainage rare.
• Morton ? melanoma
• Cabanas ? penile carcinoma

8
(No Transcript)
9
Sentinel lymph node

• The lymphatic effluent of a tumour drains
  preferentially to one (or more) sentinel lymph
  node(s).
• The sentinel node accurately reflects the disease
  status of the entire nodal basin.
• Offers opportunity for enhanced pathological
  evaluation.

10
SLN localization

• Radiopharmaceutical injection ? uptake into
  lymphatics ? phagocytosis retention by lymph
  node.
• Minimal diffusion/absorption.
• Depends on particle size.
• Detectable by gamma camera (lymphoscintogram)
  by handheld gamma probe.

11
SLN localization

• Vital blue dye injection ? uptake into lymphatics
  ? retention by lymph nodes.
• Significant diffusion, absorption passage.
• Rapid
• Visible
• Complementary to radiopharmaceutical

12
Identification of the Sentinel Node
Injection of radiocolloid and intraop blue dye
13
Intraop Identification of Sentinel Node (s)
Gamma Probe
14
(No Transcript)
15
Blue Dye

• Allergic reactions
• Inform anaesthesia drop in saturation monitor
• Patient may appear ashen, cadaveric ? inform
  recovery room nurses
• Counsel patient re blue-green urine/BM
• Skin Tatooing

16
Validation of SLN hypothesis

• Does SLN reflect disease status of the nodal
  basin?
• Can SLN be consistently identified?
• What is the risk of a false negative SLNB?
• Can SLNB technique be widely disseminated with
  acceptable success accuracy?

17
Validation of SLN hypothesis

• Giuliano et al, Ann Surg 1999
• Negative SLN ? positive ALN 1/1087
• Veronesi et al, Lancet 1997
• Negative SLN ? positive ALN 3
• Krag et al, NEJM 1998
• Negative SLN ? positive ALN 3
• Risk of false negative ALND 3-10

18
Validation of SLN concept

• Cox et al, J Am Coll Surg 1997
• 96 successful identification of SLN
• Giuliano et al, J Clin Onc 1997
• 99 successful identification of SLN
• Veronesi et al Lancet 1997
• 98 successful identification of SLN

19
Implementation dissemination

• Krag Giuliano identified learning curve in
  both identification rate false negative rate.
• However, validation series, multicentered trials
  meta-analyses have demonstrated that technique
  can be implemented with acceptable accuracy rates.

20
Learning Curves

• Data suggest increased volume lead to decreased
  failure rates
• COX learning curve- logistic regression on
  mapping failures
• lt3 SLN biopsies/month 86 success rate
• 3-6 SLN biopsies/month- 89 success rate
• gt6 SLN/biopsies/month- 97 success rate

21
Learning Curve FN Rate

• Four multicenter trials
• Decrease in False Negative rate to or lt 5 after
  20-30 procedures
• A minimum of 25 cases with completion ALND is
  recommended

22
Is SLNB better than ALND?

• Enhanced staging single/small number of nodes
  enables serial sectioning with H E, and also
  immunohistochemical staining (IHC).
• Most series nodal positivity rates 10-25 higher
  than ALND.
• Reflects historical rates of serial sectioning
  entire ALND.

23
Pathology
24
Micrometastasis
25
Revised AJCC Staging

• pN0
• pN0 (i-)-negative IHC
• pN0 (i) positive IHC but no cluster gt 0.2 mm
  (Isolated Tumour Cells)
• pN1mi micrometastases (greater than 0.2 and none
  greater than 2.0 mm)
• pN1 1-3 positive nodes

26
Is SLNB better than ALND?

• Morbidity ALND is the leading cause of decreased
  cancer-specific quality of life.
• Postoperative complications
• Lymphedema 3-10
• Numbness 30-60
• Chronic pain/neuritis 20-30

27
Is SLNB better than ALND?

• Burak et al Am J Surg 2002 Temple et al Ann
  Surg Onc 2002
• Significantly less lymphedema, numbness pain.
• Veronesi et al NEJM 2004 significantly fewer
  patients with edema, pain, numbness, improved
  mobility cosmesis

28
ACOSOG Z010

• 5237 patients
• Surgical outcomes at 30 days and 6 months
• Anaphylaxis 0.1
• Wound infection 1.0
• Seroma 7.1
• Hematoma 1.4
• Axillary parasthesias 8.6
• Lymphedema 6.9

Ann Surg Oncol13(4) 2006
29
Unresolved issues

• Patient selection
• Implementation accreditation.
• Importance of micrometastatic disease.
• Technical controversies variations.
• Intraoperative SLN evaluation.
• Internal mammary nodes
• What to do with a positive SLN?

30
Clinical trials

• NSABP B-32 studies node negatives
• Survival, regional control toxicity of SLNB
  versus ALND.
• Prognostic value of IHC.
• Technical success rate.
• Target accrual 5400 patients

31
NSABP- B-32
Accrual 5400 patients
32
Clinical trials ACOSOG

• Z0010 all patients SLNB ? risk of negative SLNB
  no further surgery with or without positive
  micrometastatic disease. Target accrual 5300
• Z0011 all patients SLNB ? risk of positive SLNB
  and full ALND versus no ALND (with breast XRT
  adjuvant therapy). Target accrual 1900

33
Integration of Sentinel NodeCanadian Survey
Results

• Canadian Survey
• 61 response rate
• 1413 surgeons- 490 treated breast cancer
• Doubling of of surgeons performing SLN over
  five year period

34
2006 Survey Results

• 76 learned SLN procedure from mentor or Formal
  course
• 56 cited inadequate resources as a deterrent
• Specifically lack of gamma probe or nuclear
  medicine resources

35
Is Sentinel Node Biopsy the Standard of Care?

• Veronesi- RCT N Engl J Med. 2003 Aug
  7349(6)546-53.
• Underpowered ( n516)
• Short follow-up
• Definitive trial-----NSABP 32
• Trial 23-01----European IO, Italy
• ALMANAC Trial- Quality

36
National Surgeons Survey
No
Yes
37
Canadian Survey 2006
of Surgeons
Quan, Wright, Hodgson,Lovrics,Porter
38
What to do with a positive SLN?

• In patients with a SLN routine HE
• 30-40 disease on completion ALND ? ALND
• If micrometastatic disease 10-35 ?
• If ITC lt10 risk of additional ve nodes ?
• Literature difficult to interpret.
• NSABP/ACOSOG studies

39
Nomogram for Predicting additional Axillary
Metasases

• Memorial Sloan Kettering Cancer Center
• Primary characteristics size, grade, LVI, ER,
  multifocality
• SLN number positive negative, detection
  method.
• Calculates risk of further positive nodes in
  completion axillary dissection.
• Van Zee et al. Ann Surg Oncol1140-1151, 2003

40
Sentinel lymph node biopsy

• Its here.
• More accurate less morbid.
• Accepted as standard of care.
• Unresolved issues variances in techniques,
  implementation/standards, positive SLN patient
  selection.