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

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

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

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

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

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

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

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?

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

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

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

ACOSOG Z1071(Alliance)Trial

ACOSOG Z1071(Alliance)Trial Multicenter clinical trial 756 women, clinical T0-T4, N1-N2, M0 breast cancer and received neoadjuvant chemotherapy from 2009-2011 663 patients with cN1 disease Primary end point: - False negative rate(FNR) for SLN dissection in patient with clinical N1 disease with at least 2 SLNs examined => 12.6% (95% CI 9.85-16.05%) SLN detection rate 92.9% Axillary pCR rate 41% Boughey et al, JAMA 2013

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

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

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

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

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

SENTINA Trial Kuehn et al, Lancet Oncol 2013

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

SN FNAC Trial (2014) JCO 2014 Prospective multicentre cohort study 153 patients with T0-3 N1-2 disease were recruited from 2009-2012

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

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

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

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

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%

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

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

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

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

Thank you!