uptodate lecture with review of the latest sudies in axillary managment of breast cancer patients 2021

1. AXILLARY MANAGEMENT
DECISION MAKING
DR ANAS ABURUMMAN
breast surgical oncologist
Dr.anasaburumman@yahoo.com
Jordan /Alhussein medical city center/breast surgery unit
March /2021

2. INTRODUCTION
• The status of the axillary lymph nodes is one of the most important
prognostic factors in patients with breast cancer.
• approximately one in four patients with clinically negative lymph
nodes will have pathologically identified nodal metastases
• Axillary dissection has traditionally been used in breast surgery to
obtain lymph nodes.
• Sentinel lymph node biopsy has replaced axillary lymph node
dissection in most patients with early stage breast cancer.

3. Axillary lymph nodes
• (ALNs) receive 85 % of the lymphatic drainage from all quadrants of
the breast; the remainder drains to the internal mammary,
infraclavicular, and/or supraclavicular lymph nodes.
• The likelihood of ALN involvement is related to tumor size and
location, histologic grade, and the presence of lymphatic invasion.

4. Tumor size & LNs involvment
• Larger tumors are associated with a higher likelihood of axillary involvement,
• In a series of 2282 women with invasive breast cancer or ductal carcinoma
• the incidence of ALN involvement was as follows :
• ●Tis – 0.8 %
• ●T1a – 5 %
• ●T1b – 16 %
• ●T1c – 28 %
• ●T2 – 47 %
• ●T3 – 68 %
• ●T4 – 86%

5. Axillary management for Breast cancer Patients
Sub categorized into :
>Patients treated by Surgery as the First Line of Treatment in early
stage breast cancer .
>Patients treated by surgery post neoadjuvant chemotherapy .

6. Primary surgery in early Breast cancer.
• Assesment of the axilla
• Physical examination
• Axillary Imaging
• FNA vs CNBX

7. Concept of SLNB.
• Step wise spread
• Orderly & Predictable pattern of
lymphatic drainage , functioning
and effective filter 1st LN .

8. Overview of SLNB in breast cancer
• The SLNB technique has been developed and validated over the past
three decades.
• It has been demonstrated to be feasible, accurate, and less morbid
than (ALND).
• It has been adopted by medical centers worldwide as the standard
initial approach for patients with early-stage breast cancer.
• A systematic review of 69 trials of SLNB, including 8059 patients,
showed that sentinel lymph nodes could be identified in 95 % of
patients with a false negative rate of 7.3 %.

9. Indications of SLNB
• Early stage breast cancer with clinically negative nodes
• DCIS with planned mastectomy or suspicious features : two groups
of women undergoing breast surgery for DCIS may benefit from SLNB.
• DCIS with planned mastectomy
• DCIS with suspicious features

10. Contraindications to SLNB
• Clinically positive nodes :
• pathologically proven to contain metastatic cancer should undergo ALND
for axillary clearance, rather than SLNB.
• Locally advanced and inflammatory breast cance :
• T3 tumors is not absolute contraindication to SLNB, as long as the axilla is
clinically negative .
• T4 tumors are absolutely contraindicated.

11. Special circumstances
• Multicentric disease : Multicentric disease is not a contraindication to SLNB .
• Previous breast and axillary procedures for benign conditions :
• in these patients, we perform preoperative lymphoscintigraphy prior to SLNB.
• Recurrent breast cancer and previous axillary procedures :
• there are accumulating reports of successful second SLNB in patients with local recurrences of breast cancer
following a previous SLNB or ALND.
• SLNB can be as accurate as in patients without prior axillary surgery when a sentinel node can be identified.
• Male breast cancer : the principles guiding SLNB in women appear to apply to men.
• Pregnancy :
• SLNB is best avoided in women who are pregnant because of potential teratogenic effects on the developing fetus
from isosulfan blue dye and a lack of safety studies on other tracer agents .
• Although some consider the use of methylene blue or radioactive colloid to be safe for the fetus in pregnant
women with breast cancer,
• In one retrospective study, 25 pregnant women with breast cancer were injected with methylene blue, radioactive
colloid (16), or another type of tracer (2) during SLNB procedures .There were 25 livebirth infants, 24 of whom were
deemed healthy at delivery; one infant had a cleft lip not attributed to the injections

12. VALIDATION AND PATHOLOGY
• The SLNB technique is endorsed by multiple guidelines as an
alternative to ALND for the diagnosis of axillary metastases in patients
with clinically node-negative early breast cancer .

13. Pathologic analysis of nodal metastases.
• Isolated tumor cell clusters — defined as small clusters of tumor cells not greater than
0.2 mm
• Micrometastases : defined as a metastatic deposit >0.2 mm but ≤2.0 mm. If present, it is
designated as pN1mi
• Macrometastases : (classically designated as "node-positive") is defined by any tumor
cell deposit >2.0 mm.
• Extranodal extension : defined as invasive tumor cells or clusters that are present
outside of the lymph node capsule and parenchyma.
• One retrospective study of over 1000 patients found that the presence of extranodal
tumor deposits were strongly associated with four or more positive nonsentinel lymph
nodes among patients with one to two positive sentinel lymph nodes .
• Occult metastatic disease : Occult micrometastases refer to nodal metastases that are
not seen on initial H&E examination but are detected subsequently by additional levels
or by IHC staining or reverse tPCR.

14. Techniques used in SLNB
• A properly performed SLNB identifies patients who need further
axillary clearance, while sparing others a potentially morbid (ALND) .
• Proper surgical technique in SLNB minimizes the risk of understaging
and undertreating patients, which in turn influences outcomes
• SLNB typically begins with injection of one or two tracers into breast
skin or parenchyma either in the vicinity of the tumor or under the
areolar plexus.
• Sentinel lymph nodes are then identified as those first receiving
drainage from the tumor by the presence of tracer and removed

15. Injection of tracer agents.

16. The sections below describe best practices for each
tracer agent as suggested by the experts in the field
• Blue dye : (1% isosulfan blue or diluted methylene blue).

17. Dual technique for detection of SLN(s):
(a) axillary lymph node(s) that are both
stained blue and emitted radioactivity
• Radioactive colloid
• both filtered and unfiltered technetium sulfur colloid agents are
normally used , When available, unfiltered radioactive colloid is better
for SLNB because the larger particles in the unfiltered solution are
trapped better by the sentinel lymph nodes

18. newer techniques
• ICG –In a meta-analysis of 12 nonrandomized comparative studies, ICG was
equal to or better than radioactive colloid in localizing sentinel lymph nodes and
tumor-positive sentinel nodes

19. ICG
The fluorescence method has four major advantages
over the standard radioactive technique:
1.it works without radiation and its danger.
2. it can be applied directly in the operating room
without preoperative scintigraphy.
3. it allows reliable identification and visual
localisation of sentinel lymph nodes by ICG
fluorescence.
4.lymphatic flow can be observed transcutaneously
in real time, allowing pre- or intra-operative
mapping.’

20. • SPIO :The magnetic tracer agent :
• In a meta-analysis of seven randomized trials, the SPIO technique was not
inferior to the standard technique in identification rate (97.1 versus 96.8
percent), The mean discordance rate between the two techniques was 3.9 .
• Microbubble contrast :
• contrast-enhanced ultrasound and followed to identify and biopsy axillary
SLN .
• In a meta-analysis of five studies, this technique identified sentinel lymph
nodes in 9.3 to 55.2 % of patients with a sensitivity of 61 to 89 percent and a
FNR of 6.6 to 39 percent .
• Comparative studies with a standard technique are required to validate this
technique.

21. CONTROVERSIAL ISSUES
• Single versus dual technique :
• In a systematic review of the data the use of both blue dye and
radiocolloid was associated with an almost significant trend toward
fewer false negative results (7 versus 9.9 percent, p = 0.07) .
• the use of dual tracers may be warranted in situations where the
sentinel node identification rate is expected to be low and the FNR
high . ???

22. CONTROVERSIAL ISSUES
• Lymphoscintigraphy : ???
• Optimum number of sentinel lymph nodes ???
• Intraoperative evaluation of sentinel lymph nodes :
• Although several intraoperative techniques can be used to identify a
positive sentinel node , cell smears, cytokeratin staining, and/or
frozen sections
• the average false negative rate of intraoperative sentinel lymph node
evaluation is 25 % , there were 2 percent false positives which lead to
unnecessary ALND.
• So Permanent sections remain the gold standard

23. MANAGEMENT AFTER SENTINEL LYMPH NODE
BIOPSY
• No sentinel node metastasis ???
• Occult metastasis ???
• One or two sentinel node metastases : (hot topic )!!!
• Two randomized trials, the ACOSOG Z-0011 trial and the International Breast
Cancer Study Group 23-01 (IBCSG 23-01) trial, demonstrated that many of these
patients with one or two metastatic sentinel nodes can safely avoid a completion
axillary node dissection provided they are (Z0011 eligible criteria). ? If its not
eligible ? Then what next ?
• Sentinel node metastasis with extranodal extension ??? Even if one sentinel !!!
• Sentinel node metastasis with large tumor ??? Even if one sentinel !!! Why?
• Three or more sentinel node metastases

24. ROLE OF RADIOTHERAPY
The AMAROS trial showed axillary radiation to be
an acceptable alternative to ALND in patients who
have positive sentinel node(s) but do not meet the
Z0011 criteria.
For those who meet the Z0011 criteria, axillary
radiation is likely to add morbidity without
conferring any additional benefit compared with
whole-breast irradiation alone.

27. Case scenario : 1
• A 44 yrs old female pt , presented with RT breast cancer measuring 3
cm , IDC .
• On examination : no palpable axillry LNs
• On Imaging : multiple pathological axillary LNs.
• FNA results : malignat cells present
• Axillary decision ???

28. Case scenario :2
• A 47 yrs old female pt present with RT breat mass measuring 3 cm ,
investigated and found to have IDC .
• On examination : no palpable axillary LNs .
• Imaging studies :no suspicious LNs.
• Done for her breast pathology BCS
• SLNB revealed 2 positive LNs.
• What next . ???
• Completion ALND VS axillary radiation therapy VS no further axillary
surgery.

29. Case scenario :3
• A 55 yrs old female pt ,presented with left breast mass measuring 4
cm , located in retroareolar area , CNBX revealed IDC .
• NO palpable axillary LNs .
• On imaging study: no suspicious axillary LNS .
• Pt treated by mastectomy +SLNB
• SLN REVEALED two positive LNS
• Whats next ???

30. Case scenario : 4
• A 35 yrs old female pt ,presented with RT breast cancer measuring 2
cm , IDC .
• NO palpable axillary LNs
• On imaging : no suspicious pathological LNs
• Treated by BCS +SLNB .
• SLNB result 1 positive LNs associated with gross extranodal
extension
What next ???.

31. Axillary management post NAC.

32. Introduction
• PST will not only induce tumour downstaging to facilitate BCS but may also
achieve (pCR),which is predictive regarding (DFS) and (OS).
• pCR may occur in about 20–45% of PBC cases,regarding the incidence of
pCR in axillary lymph nodes, similar but not necessarily concordant rates
are found .
• While breast surgery within the new tumour boundaries after PST
downstaging is of undisputed safety, controversial issues remain with
respect to axillary surgery approaches.

33. SLNB in NAC controversial questions
1. What is the optimal timing of SLNB in the neoadjuvant setting?
2. Does SLNB provide an accurate assessment of nodal status when
performed after PST ?
3. Is there a difference between patients with initially node-negative
vs. node-positive disease?
4. Which method should be chosen to confirm nodal status prior to
PST?

34. MSKCC Neoadjuvant Therapy
nodal pCR by subtype
Clinical Stage I-III breast cancer, enrollment 11/2013-7/2015
245/440 pts had completed surgical therapy

35. Axillary Node Downstaging
NSABP B18
Can we do SLN biopsy after NAC and avoid ALND?

36. SNB Before Neoadjuvant Therapy
Disadvantages
• Requires two surgical procedures
• Does not take advantage of the potential downstaging effects on lymph nodes
• Uncertain prognostic value of negative nodes after NAC if the SLN was the only positive node and was
removed

37. SNB after Neoadjuvant Therapy
Arguments in Favor
• This avoids an additional surgical procedure
• preserves the prognostic information obtained from the status of the
sentinel nodes after neoadjuvant therapy

39. •Accurate assessment of SLN & Techniques to
optimize SLNBX following NAC .

40. SLN Biopsy After Neoadjuvant Therapy
cN1 convert Cn0

41. IHC

42. Used methods to identify
clipped nodes:

43. SLN biopsy after NAC - cN1 convert to cN0
suggestions to minimize the FNR
• Dual agent mapping
• Normal exam after chemotherapy
• Remove ≥ 3 SN
• Include IHC detected disease as node
positive
• Leave a clip at time of biopsy and localize for
SLN

44. Evidence based _ accuracy OF SLNB post NAC.

45. Sentinel Lymph Node Biopsy After
Neoadjuvant Therapy
A Practical Approach
• Clinical node negative ...
●If the SLNB result is negative (ypN0), no further axillary evaluation is required.
●If the SLNB is positive (ypN+), we proceed with ALND.
●Patients in whom sentinel node mapping is not technically successful
require an ALND.

46. Sentinel Lymph Node Biopsy After
Neoadjuvant Therapy
• Clinically node positive (N1) converts to node negative
management of the axilla includes:
•Patients who remain clinically node positive (ycN1) after NACT should undergo an ALND.
•Patients who are clinically node negative after NACT (ycN0) should undergo axillary US after NACT.

47. Axillary US post NACT in pts whom converted from CN+/CN0
• approach is as follows:
●For those with abnormal post-treatment axillary US, ALND should be
performed, which may be done at the time of breast surgery.
●For those with negative or uncertain axillary US results, post-
treatment SLNB as well as removal of any clipped or other marked
nodes should be planned. This may be performed at the time of breast
surgery, with intraoperative assessment of the sampled nodes, if
possible.

48. Rationale for Axillary US POST NAC ?
• limiting SLNB to those with normal US and pursuing ALND in others decreases
the FNR associated with SLNB from(13 to 10) percent.
• The ACOSOG Z1071 trial evaluated the accuracy of axillary US in 611 patients who
presented with cN1 or cN2 disease and underwent US, SLNB, and ALND following
NACT , The major findings were that patients with suspicious nodes on post-NACT
US were very likely to have positive nodes at surgery (72 %) and to have a greater
number of positive nodes and larger nodal metastases than patients with normal-
appearing nodes.