A comprehensive approach to the management of axillary disease in breast cancer and the latest updates.

1. MANAGEMENT OF AXILLA IN CARCINOMA BREAST
:CURRENT PERSPECTIVE
Presented by
Paras Bhandari
Junior Resident III
Moderator
Dr. Gitika Nanda Singh (MS,MCh)
Asst. Professor
Department of Surgery(Gen.)
KGMU,Lucknow

2. Overview
• Anatomy
• History
• Preoperative axillary assesment
• ALND
• SLNB
• Important Trials
• SLNB IN SPECIAL SITUATION
• Future Perspectives in SLN
• Axillary Sampling
• Conclusion

3. ANATOMY

4. Lymphatic Drainage

5. Lymphatic of Breast
i. Superficial lymphatics includes
Cutaneous Plexus(Dermis)
Subcutaneous Plexus(Subcutaneous space)
Drain in axillary L.N
ii Deep Lymphatic plexus
Glandular plexus (lobes and ducts)
Fascial Plexus(over pectoralis fascia)
The superficial injection techniques are based on that both
gland and skin have a common embryonic origin and
therefore share the same lymphatic drainage
(Tanis et al.; Quadros & Gebrim).
• Lymphatic Drainage of the Breast from Theory to Surgical Practice Int. J.
Morphol.,27(3):873-878, 2009.

6. PRE OPERATIVE ASSESMENT

7. Pre-Operative Assessment of Axilla
Zhang YN1 et al Sensitivity, Specificity and Accuracy of Ultrasound in Diagnosis of Breast Cancer Metastasis to the
Axillary Lymph Nodes in Chinese Patients.. Ultrasound Med Biol. 2015 Jul;41(7):1835-41. doi:
10.1016/j.ultrasmedbio.2015.03.024. Epub 2015 Apr 29.
Technique Sensitivity Specificity
Clinical Examination 31.6%
Hr-USG Axilla 69.4% 81.8%
Hr-USG Axilla + FNAC 78.9% 100%
Mammography 14% 84%
CT Scan 93% 57%
Dynamic Contrast
Enhanced MRI
93% 62%
2Nan Fang Yi etal [Value of mamography, CT and DCE-MRI in detecting axillary lymph node
metastasis of breast cancer 2016 Apr;36(4):493-9

8. USG Metastatic nodes
Normal Lymph node
• Smooth
• Hypoechoic cortex
< 3 mm
• Echogenic central
hilum

9. USG Metastatic nodes
Metastatic Lymph
node
• Hypoechoic cortex
> 3 mm
• Absence of
echogenic central
hilum
• Abnormal/
Hyperemic blood flow

10. Mammography
Normal Lymphnode
• Elongated
• Central
hypointense
• hilum

11. Mammography
Abnormal Lymphnode
• Round
• Eccentric hila/loss of
hila
• Microcalcification

12. HISTORY

13. Milestones of Axillary Lymph node dissection
• Rudolf Virchow first hypothesized
centrifugal expansion of breast cancer in
axillary lymphnode
• William Stewart Halsted advocated
"Radical Mastectomy with axillary dissection“
• Bernard Fisher 1971 challeged Halstead
hypothesis
• Giuliano et al. 1994 propogated Sentinel Biopsy in Breast
cancer
Robert E. Mansel et al (2000) History, Present Status and Future of Sentinel Node Biopsy in
Breast Cancer: The Mary Béves Lecture, Acta Oncologica, 39:3, 265-268

14. Tumour Size and axillary Metastasis
De-escalation of axillary surgery in early breast cancer Kyoto Breast Cancer Consensus
Conference 2016

15. • Staging
• Prognosis: Most powerful predictor of recurrence and
survival
• Determines therapeutic decision making- extent of
axillary surgery, systemic therapy, radiation)
De-escalation of axillary surgery in early breast cancer Kyoto Breast Cancer Consensus
Conference 2016
Importance of axilla Management

16. AXILLARY LYMPH NODE DISSECTION
(ALND)

17. Axillary Lymph node Dissection(ALND)
Removal of level I and II lymph nodes in carcinoma breast
patients with clinically positive nodes
Current indications for ALND
• Clinically node-positive axilla
• Occult breast cancer: axillary node metastasis
• Inflammatory/T4/T3 breast cancer
• SLN positive patients
• Facility of SLNB not available

18. • Failed SLN mapping
• Inadequate prior ALND
• After neo adjuvant chemotherapy
• Axillary recurrence following previous breast cancer
treatment

19. • Axillary lymph node dissection
– Standard: Level 1 and 2 dissection
– Level 3 dissection if
• Enlarged level 3 nodes
• Bulky levels 1 and 2 nodes
Adequate ALND: >10 lymph nodes removed

21. Morbidity of ALND
50% to 70% of patients undergoing ALND will have some
complaints
Early
• Skin erythema
• Prolonged drainage or Seroma
• Wound infection
Delayed
• Arm edema (16%)
• Shoulder dysfunction (17%)
• Pain (25%)
• Chest wall and arm numbness (78%)
Complications of Level I and II Axillary Dissection in the Treatment of Carcinoma of the Breast Ann
Surg. 1999 Aug

22. SENTINEL LYMPHNODE BIOPSY
(SLNB)

23. NSABP B-04 TRIAL (BERNARD FISHER MD et al 1971)
AIM-COMPARISION OF RADICAL V/S TOTAL MASTECTOMY
TIME PERIOD 25 YEARS

25. Sentinel Lymph node
• “Node on Watch”.
• First node to receive
cancer cells.
• If negative, the upstream
nodes are negative
99 /100 times
Amit Goyal Management of the axilla in
Patients with breast cancer Indian J Surg
(November 2009) 71:328–334

26. History of Sentinel Lymph node
• Seaman/Powers 1955 first echelon node, nodal basin with
radioactive colloid gold
• Gould in 1960 labeled first-echelon node the “sentinel
node”
• Cabanas in 1977 identified specific groin node in primary
penile cancer
• Morton 1992 demonstrated intraoperative mapping in
humans with melanoma using dye
Cabanas : AN approach to the treatment of penile carcinoma
Morton et al: Technical details of intraop lymphatic mapping for melanomaGould:
observations on a sentinel node in parotid cancer

27. Benefits of SLND
• Reduces the morbidity of axilla dissection: lymphedema ,
shoulder dysfunction, numbness, seroma and chronic pain
• Can identify patients with proven node positive disease
who may benefit from ALND
• Cost and time effective
• Provides reliable pathologic staging of axilla with
Identification rate 95% False Negative rate 5-10%
Amit Goyal Management of the axilla in Patients with breast cancer Indian J Surg
(November 2009) 71:328–334

28. Contraindications
Absolute
Clinically positive nodes
Inflammatory breast cancer
Relative
Locally advanced and inflammatory breast cancer
Neoadjuvant chemotherapy
Previous breast and axillary procedures for benign conditions
Recurrent breast cancer and previous axillary procedures
Pregnancy
Surgeons experience and learning curve
George M Filippakis et al Contraindications of sentinel lymph node biopsy: Áre there any really?
alWorld J Surg Oncol. 2007; 5: 10.

30. Technique
Four steps
1 : SLN identification
2 : SLN Removal
3: Intra-op pathology of SLN
4: Management

31. Reagent Used Sensitivity Specificity Accuracy
Blue Dye 82% 60% 68%
Patent violent (Lymphazurin ®)
– Methylene blue
• Radio-pharmaceutical 91%
– 99mTc Sulfur colloid
– 99mTc antimony colloid
• Combination 95% 73% 83%
Blue dye versus combined blue dye radioactive tracer technique in detection of sentinel L.N. in breast
cancer Eur J Surj Oncology 2004
Identification

32. • Radiotracer element combined with Organic or inorganic
carrier
• Smaller the size more the speed of flow
• Optimal size 10-100 nm
Volume Used
Radiotracer- Day before 2.5 miC
Preop 0.5 miC
Blue dye 4-5 ml
• FREGNANI, J. H. T. G. & MACÉA, J. R. Lymphatic drainage of the breast: from theory
to surgical practice. Int. J.Morphol., 27(3):873-878, 2009.

33. Site of Injection
IR FNR
Peritumoral 72% 8.3
Subdermal 92% 7.8
Intradermal 95.3 6.5
Peritumoral+Subdermal 93.2
Periareolar+Intradermal 98%
Comprasion of different injection sites of radionuclide for sentinel lymphnode detection in
breast cancer Mudun A Clin Nucl Med 2008

34. Procedure

35. HOW MANY NODES?
Number of Dissected
SLN
False Negative
rate %
Accuracy %
1 10.8 96.3
2 5 98.3
3 3.5 98.7
4 or more 0 100
How Many Sentinel Lymph Nodes Are Enough for Accurate Axillary Staging in T1-2 Breast
Cancer? Eun Jeong Ban Journal of Breast Cancer 2011 December

36. Non Visualisation of Sentinel Lymphnode
• Shine through” from primary tumor can obscure
identification
• Tumor filling a node, distorting architecture, could
redirect lymphatic flow
• Tumor size can directly compress draining lymphatics
• Technical Incompetence
Isabelle Brenot-Rossi etal 2009Nonvisualization of Axillary Sentinel Node During Lymphoscintigraphy: Is There a
Pathologic Significance in Breast Cancer?, m jnm.snmjournals.org

37. Pathological Examination of SLN
Rapid/ intra-op pathology to aid one-stage operation
• The value of touch imprint cytology and frozen section for intra-operative evaluation of axillary sentinel lymph
nodes. Pol J Pathol. 2010;61(3):161-5
• Cytokeratin on Frozen Sections of Sentinel Node May Spare Breast Cancer Patients Secondary Axillary Surgery
Pathology Research InternationalVolume 2012 (2012), Article ID 802184,
• Intraoperative diagnosis of sentinel lymph node metastases in breast cancer treatment with one-step nucleic acid
amplification assay (OSNA) Arch Med Sci. 2016
Technique Sensitivity(%) Specificity(%)
Touch Imprint Cytology 71.4 100
Frozen Section(FS) 87 98.5
Rapid Cytokeratin Immune
Staining(RCI)
80 97.5
FS+RCI 87 100
OSNA(One step nucleic acid
amplification )
99-100 90-100

38. Isolated Tumour Cell
(pN0(i+))
Micrometastasis
(pN1mi )
Macrometastasis
Clusters of tumor cells
< 0.2 mm or
nonconfluent or nearly
confluent clusters of
cells <200 cells in a
single histologic lymph
node cross section
Nodal involvement
with metastatic
deposit >0.2 mm but
<2.0 mm.
Nodal involvement
(classically designated
as "node-positive") by
any tumor cell deposit
>2.0 mm.
Recent consideration :-
Occult metastatic disease (pN0) Nodal metastases detected only by
immunohistochemical staining or reverse transcriptase polymerase
chain reaction
("Z-0011-eligible" criteria and NCCN 2017 Guidelines)
Interpretation result of SLND

39. MANAGEMENT AFTER SENTINEL LYMPH NODE BIOPSY
Completion ALND
• >2 metastatic sentinel lymph nodes on SLNB.
• 1-2 metastatic sentinel lymph nodes on SLNB but who do
not desire whole-breast irradiation.
No ALND
• A T1 or T2 (≤5 cm) primary breast cancer
• <3 metastatic sentinel lymph nodes on SLNB.
• Breast conserving surgery
• whole-breast irradiation
("Z-0011-eligible" criteria and NCCN 2017 Guidelines)

40. IMPORTANT TRIALS

41. NSABP B-32
AIM-Whether SLN resection achieves same survival and
regional control as ALND
Time Period 96 months
Inclusion Criteria
• Clinically node negative
• Age (≤49 years, ≥50 years)
• Type of surgery (lumpectomy, mastectomy)

43. MILAN TRIAL (UMBERTO VERONESI, M.D. et al 1986)
• AIM Comparision of Radical Mastectomy with Quadrantectomy
• Inclusion criteria Clinically negative nodes
Age < 70 yrs
Breast Cancer < 2 cm
• Time Period 8 YEARS
ALND NO ALND
Over all Survival 83+2.2 85+2.1
Disease Free Survival 77+2.4 80+2.4

44. ACOSOG Z0011 TRIAL (Guliano et al)
• AIM: impact of completion ALND on survival of patients
with SLN metastasis in breast cancer.
• Time Period 5 Years (1999-2004)
• Sample 891
Inclusion Criteria
• T1 or T2 breast cancer;
• no palpable adenopathy;
• Patients with sentinel lymph node-positive disease were
randomly assigned to ALND or no further axillary surgery

47. AMAROS61
AIM: Comparison of ALND with SLNB+RT
Year -2001
Sample 1425
Inclusion Criteria T1 or T2 breast cancer;
no palpable adenopathy;
primary tumour treated with breast-
conserving therapy or mastectomy

50. SLNB IN SPECIAL SITUATION

51. Post NACT SLN
Still under study
Studies carried out
Study Type Prechemo node Identification False Negative
identification rate (IR) rate (FNR)

52. In Study conducted in SGPGI 2015 concludes
SLNB in post-NACT N0 patients was not found robust in
staging the axilla
• Minimum acceptable quality standards for staging axilla,
SLN-IR of 90% and SLN-FNR of 10%
• Patients with index stage T3,N0-1 are
exception to this.
• (Pre-NACT) skin involvement (T4b),
matted axillary nodes (N2a) and LVI
predict high-risk of non-identification
and false-negative SLNB.
Gaurav Agarwal etal 2015 Sentinel Lymph Node Biopsy (SLNB) after Neo-adjuvant Chemotherapy (NACT) in Large/ Locally Advanced
Breast Cancer Patients: Results of a Validation Study San Antonio Breast Cancer Symposium - 2015

54. Locoregional Recurrence following SLN

56. Future Perspectives in SLN
• Newer technologies for lymphatic mapping
Indocyanine green fluroscent
Super paramagnetic iron oxide nanoparticle
• Omission of SLN Biopsy in early Breast Cancer
SOUND trial(tumour size<2 cm)
INSEMA Trial(tumour size<5 cm)
(Prof E P Mamounas MD etal August 14, 2017 Current approach of the axilla in patients with
early-stage breast cancer Published Online University of Florida Health Cancer Center—
Orlando Health,and University of Central Florida, Orlando, FL, USA

57. Year 2014
Sample
1900
Planned
POSNOC64
(Ongoing)
Inclusion Criteria
Invasive breast cancer
(≤5 cm);no palpable
adenopathy; primary
tumour treated with
breast-conserving
surgery or mastectomy
Design
Patients with sentinel lymph
node-positive disease were
randomly assigned to axillary
therapy (surgery or
radiotherapy) or no further
axillary therapy
Aim
• Learn more about the side effect of
treatment of axilla node
• Effect of axillary treatment on Quality of life

58. AXILLARY SAMPLING
Blind technique and relies on palpation to removal
lymph nodes.
Indication Fail SLNB
No Facility of SLNB
Largest node (min 4) excised
Accuracy 95%
Sensory loss and lymphoedema worse after four
node sampling compared with SLNB
Monypenny IJ et al (2005) End of 4 node sampling?- Comparative morbidity
versus sentinel lymph node biopsy in the ALMANAC trial. Proceedings of the
Nottingham Breast Cancer Conference 2005

59. Sentinel node biopsy versus low axillary sampling in women
with clinically node negative operable breast cancer
(V.Parmar et al 2004-11)
• Excision of all fibrofatty tissue overlying the second
digitation of serratus anterior below the intercostobrachial
nerve
• Done before pre-operative injection of radioactive colloid
and injection of blue dye
• False Negative Rate not significant(p=0.56)
• effective and low cost procedure that minimizes axillary
surgery and can be implemented widely

60. CONCLUSION

61. NCCN Guidelines® Insights Breast Cancer, Version 1.2017

62. Schematic of progressive de-escalation of axillary surgery
De-escalation of axillary surgery in early breast cancer Kyoto Breast Cancer Consensus
Conference 2016

63. Switch to new paradigm
“maximum tolerable treatment”
“minimum effective treatment.”

64. THANK YOU