1. JHSGR 15/10/2016 Wong Lai Shan Tuen Mun Hospital
Should Sentinel Lymph Node Biopsy be used in Node-positive Breast Cancer after Neoadjuvant Chemotherapy?
Good afternoon everyone, I am Candy Wong from Tuen Mun Hospital
My presentation topic today is ‘should sentinel LNB be used in node positive breast cancer after neoadjuvant chemotherapy
JHSGR 15/10/2016
Wong Lai Shan
Tuen Mun Hospital

2. Introduction
Role of sentinel lymph node biopsy(SLNB) in management of clinically node-negative breast cancer is well-established
Reliable method of identifying nodal metastasis with good accuracy and acceptable false negative rate (<10%)
–NSABP B-32 trial
Avoid unnecessary axillary dissection so as to prevent associated morbidity
Lympedema, decreased arm mobility, arm pain and numbness
SLNB has well established role in managenent of node-negative breast cancer
With equivalent overall survival, disease-free survival and local-regional control as axillary dissection

3. Introduction
How about patient with node-positive disease at presentation?
But for node positive disease, the treatment approach is different
Let’s quickly go through a case for better illustration

4. Case Ms Yau, 42/F Good past health C/O right breast mass for 6months
Physical examination:
5.5cm right breast mass without skin/muscle involvement
One enlarged mobile right axillary lymph node
Madam Yau is 42yo lady enjoiyed good past health
She presented with right breast mass with palpable right axillary LN

5. Case
Mammogram + USG: Suspicious of right breast malignancy with nodal metastasis
Core biopsy of tumour: Invasive ductal carcinoma, triple negative(ER-ve, PR-ve, Her-2 –ve)
FNAC of right axillary lymph node: Metastatic carcinoma
Whole body PET-CT: No evidence of distant metastasis
Clinical staging: cT3N1M0(Stage IIIA)
Triple assessment has been done
It turned out to be triple negative invasive ductal carcinoma with axillary nodal metastasis, but fortunately no evidence of distant metastasis

6. What will you offer? 1 Right total mastectomy with axillary dissection
Neoadjuvant chemotherapy followed by
Wide local excision and axillary dissection 2
This young lady was very keen for breast conserving treatment 4

7. Case After neoadjuvant chemotherapy
Tumour shrink to <1cm on USG
Clinically no palpable axillary LN
Wide local excision and axillary dissection done
Pathology:
High grade DCIS, no residual invasive carcinoma
Resection margin clear
Right axillary content no evidence of malignancy (0/14)
After neoadjuvant therapy completed, there is good tumour shrinkage, WLE and AD were done as planned
Pathology came back to be high DCIS only without invasive carcinoma
There was no evidence of malignancy in the right axillary LNs removed

8. Post-op
Unfortunately, patient came back FU with this disabling lymphedema after operation.
As the surgeon-in-charge, you may have a question in mind => can we prevent this?

9. Axillary dissection/clearance for nodal metastasis
Around 40% node-positive disease will be converted to pathologically node-negative disease after neoadjuvant chemotherapy
=> Axillary pathologic complete response (pCR)
*Not benefit from axillary dissection but suffer from the associated morbidity
Nowadays, offering axillary dissection for nodal metastasis in breast cancer is quite a standard practise
However, with neoadjuvant chemotherapy, around 40% node-positive disease will be coverted into node-negative
This is the group of patients who will not benefit from axillary dissection but suffer from the associated morbidity

10. What will you offer? 1 Right total mastectomy with axillary dissection
Neoadjuvant chemotherapy followed by
wide local excision and axillary dissection 2
Can SLN Biopsy helps to avoid unnecessary axillary dissection for this group of patients? 4
Neoadjuvant chemotherapy followed by
wide local excision + SLN Bx +/- AD 3

11. Actually it is already mentioned in the latest NCCN guideline updated in February this year
SLNB can be performed if axillae is clinically negative after neoadjuvant chemotherapy
However, we all know that there are technical difficulty of SLNB in post NAC axilla which will compromise the identification rate and false negative rate
There are 3 large prospective clinical trials trying to assess the feasibility and accuracy

12. ACOSOG Z1071(Alliance)Trial

13. ACOSOG Z1071(Alliance)Trial
Multicenter clinical trial
756 women, clinical T0-T4, N1-N2, M0 breast cancer and received neoadjuvant chemotherapy from
663 patients with cN1 disease
Primary end point:
- False negative rate(FNR) for SLN dissection in patient with clinical N disease with at least 2 SLNs examined
=> 12.6% (95% CI %)
SLN detection rate 92.9%
Axillary pCR rate 41%
Boughey et al, JAMA 2013

14. ACOSOG Z1071(Alliance)Trial
Boughey et al, JAMA 2013

15. ACOSOG Z1071(Alliance)Trial
In the cN2 cohort
26 patients with cN2 disease with at least 2 SLNs examined
- 12 patients had no residual nodal disease (pCR rate 46%)
- 14 patients with residual nodal disease, either confined to SLNs or remaining axillary LNs, yielded FNR 0%
* cN2 disease only represented minority of patient in the trial, was not included in the primary outcome analysis
* Restaging of the clinical nodal status after neoadjuvant therapy not mentioned
Boughey et al, JAMA 2013

16. SENTINA Trial (2013) Lancet Oncol 2013
Prospective multicentre cohort study
2234 patients who were scheduled to receive neoadjuvant therapy were recruited
1737 patients fulfiled criteria for the final per-protocol analysis

17. SENTINA Trial (2013) Study design Kuehn et al, Lancet Oncol 2013 N=662

18. SENTINA Trial (2013)
Use of dual mapping agent with radiocolloid and blue dye will increase the SLN detection rate
Kuehn et al, Lancet Oncol 2013

19. SENTINA Trial
Kuehn et al, Lancet Oncol 2013

20. SENTINA Trial (2013) Implications:
Use of dual agent for mapping increase the identification rate and decrease FNR
Harvesting 3 or more SLNs can decrease the FNR
Restaging of the clinical nodal status after neoadjuvant therapy should be considered
Kuehn et al, Lancet Oncol 2013

21. SN FNAC Trial (2014) JCO 2014 Prospective multicentre cohort study
153 patients with T0-3 N1-2 disease were recruited from

22. SN FNAC Trial (2014)
Study design
Boileau et al, ACO 2014

23. SN FNAC Trial (2014)
Results
Boileau et al, ACO 2014

24. SN FNAC Trial (2014)
Results
Boileau et al, ACO 2014

25. SN FNAC Trial (2014) Important findings:
Use of dual agent for mapping and harvesting more SLNs can decrease the FNR
Use of the Immunohistochemistry(IHC) when conventional H&E staining failed to identify micrometastasis/ITCs can decrease the FNR
Boileau et al, ACO 2014

26. Comparison of results of ACOSG Z1071, SENTINA and SN FNAC trials
ACOSOG Z1071
SENTINA
SN FNAC
Identification rate
92.9%
87.8%
87.6%
FNR - >=2 SLNs
12.6%
14.2%
4.9%
FNR - >=3 SLNs
9.1%
7.3%
N/A
FNR - Dual agent
10.8%
8.6%
5.2%
FNR - Inclusion of N0(i+)
8.4%

27. Other important factors
Tumour biology
Triple negative > Her-2+ve > hormone receptor +ve
Nodal disease burden
Patient with significant nodal disease on imaging/physical examination after neoadjuvant therapy may not be candidate for SLN biopsy
Targeted axillary dissection
Removal of the biopsy-proven positive node with SLN by placing clips to the node

28. Limitation
The three mentioned studies only demonstrated the feasibility of SLN biopsy
For patient with SLN biopsy alone after converting to node-negative disease
Lacking long term data concerning loco-regional recurrence and overall survival

29. Conclusion
With good patient selection and SLN-harvesting technique, sentinel lymph node biopsy for node-positive breast cancer after neoadjuvant chemotherapy should be considered
Multidisciplinary approach

30. Best treatment for patient
Multidisciplinary approach
Surgeon
Oncologist
Radiologist
Pathologist
Best treatment for patient

31. Thank you!