Sentinel Lymph Node Biopsy Should be Performed BEFORE Neoadjuvant Chemotherapy

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1 The London Cancer Alliance West and South Sentinel Lymph Node Biopsy Should be Performed BEFORE Neoadjuvant Chemotherapy Dimitri J Hadjiminas, MD, MPhil, FRCS (Consultant Breast & Endocrine Surgeon Imperial College NHS Healthcare Trust)

2 Sentinel Node Biopsy Initially introduced as a method of assessment of the axillary node status in small clinically nodenegative tumours Lymph Node With a combination of high identification rate and low false negative rate SNBx provides correct axillary staging in over 95% of these patients This is important as adjuvant systemic treatment and radiotherapy is often based on axillary staging Proximal Lymphatic

3 Sentinel Node Biopsy Initially introduced as a method of assessment of the axillary node status in small clinically nodenegative tumours Further studies showed that it was a safe technique for large tumours Isabelle Bedrosian et al, Pennsylvania. Cancer 2000;88:2540. Mathew Chung et al. JWCI CA. Ann Surg Oncol 2001;8(9):688.

4 Sentinel Node Bx in Large Tumours Institution Number Detection rate False Negatives Rate of node positive disease University of Pennsylvania Medical Center Isabelle Bedrosian et al, Cancer 2000;88: % 2% 59% JWCI, Santa Monica, Ann Surg Oncol 2001;8(9): % 3% 76%

5 Neoadjuvant Chemotherapy: Why Should it be any Different from any other breast cancer patient?

6 Non-uniform effect of Neoadjuvant chemo on lymph nodes Sentinel node can therefore respond better that other lymph nodes and its status may not be predictive of the post-chemo axillary status Isotope uptake by the sentinel node is a function dependent on phagocytosis of the radioactive particles and this function may be inhibited by chemotherapy Chemotherpy may induce fibrosis of lymphatics previously involved by tumour

7 MD Anderson early experience Breslin TM et al, JCO18:3480-6, 2000 N=51, successful in 43 Identification rate 82% 22 positive SN All patients underwent ANC 3 false neg SN or 12%

8 NSABP-B27 Mamounas EP et al, JCO.23: , 2005 Total N=428 Identification Rate 84.8%, N=343 Node positive on ANC=140 Node positive on SNBx=125 False negative rate 10.7%

9 Comparative data Massachusetts General Hospital, Jones JL et al, Am J Surgery. 190:517-20, Before Neoadjuvant Identification Rate 100% N=52 No False negatives After Neoadjuvant Identification Rate 80.6% N=36, successful in 29 False negatives 11%

10 Number Identification Rate False negative Fernandez A, et al node + 90% 22% Schwartz GF & Meltzer AJ node + 100% 9% Kinoshita T, node % 10% Yu JC, et al Ann Surg Oncol node pos 91.3% 9.6% Lee Seeyoun % v 97% 5.6% 20 7 node + Not mentioned 14% Yamamoto Maki et al 2007

11 Identification False negatives Fig. 1 Forest plots of SN identification rate (A), false-negative rate (B), negative predictive value (C) and accuracy (D) of an SN biopsy following NAC in breast cancer patients. The width of the horizontal line represents the 95% CI of the indi... Carolien H.M. van Deurzen, Birgit E.P.J. Vriens, Vivianne C.G. Tjan-Heijnen, Elsken van der Wall, Mirjam Albreg... Accuracy of sentinel node biopsy after neoadjuvant chemotherapy in breast cancer patients: A systematic review European Journal of Cancer Volume 45, Issue

12 Meta-analysis Van Deurzen CH et al. Eur J Cancer. 45: , studies, 2148 patients Identification Rate 90.9% False Negatives 10.5% Clinically positive lymph nodes in these patients are associated with reduced accuracy of SNBx

13 ACOSOG-Z1071 T0-4 N1-2 M0, from 136 institutions 756, eligible 708 Identification rate : 92.5% False Negative Rate : 12.8% Accuracy : 84% Presented at the SABCS, 5th December 2012.

14 SENTINA-Trial 1737 patients from 103 institutions 4 arms SNBx after neoadjuvant, 592 cn1 ycn0: IR: 80.1% False Neg: 14.2% SNBx before Neoadjuvant: IR: 99.1% (1013/1022) Presented at the SABCS, 5th December 2012.

15 5 Node Biopsy, Ahlgren J. et al. EJSO 2005;28(2): patients in total, 149 node positive on axillary clearance Number of nodes excised Number of patients classified as node positive Sensitivity 1 lymph node % 2 lymph nodes % 3 lymph nodes % 4 lymph nodes % 5 lymph nodes % Axillary clearance + 5 LN 149

16 NSABP-B04 trial 1079 clinically node-negative patients Randomised into 3 arms: Halsted mastectomy Simple mastectomy+rt Simple mastectomy 40% of Patients in Halsted Mastectomy group had histologically positive lymph nodes Only 18.6% of patients in the simple mastectomy group ever had axillary relapse

17 Z11 trial of The American College of Surgeons N=891 Axillary Clearance Sentinel node only Breast recurrence 15 8 Axillary recurrence 2 (0.5%) 4 (1%) However, 96% of patients received systemic therapy. A E Giuliano et al, Ann Surg, 2010;252:426-32

18 Pepels, De Boer et al, Ann Surg 2012;255: Compared axillary recurrence rates between patients who had SNBx only vs patients who had SN Bx and ANC or RT Only 48% of patients with sentinel node micrometastases in this study received systemic treatment RR=4.39, p<0.05

19 Neo-adjuvant Chemotherapy If SNBx is performed after Chemo then If SN is falsely negative, patients will not receive any further chemotherapy, therefore Z11 s results are not applicable

20 Straver ME, RutgersEJ et al, Eur J Cancer, 2009;45: , Neoadjuvant patients 252 node+ by pre-neoadjuvant FNA had ANC 50 had pcr (20%) 57% of Triple negative tumours 68% of HER-2 positive tumours

21 Straver ME, RutgersEJ et al, Eur J Cancer, 2009;45: , Neoadjuvant patients 75 had pre-neoadjuvant SNBx 22 had a positive SN and had ANC after chemo Only 7 of these had residual axillary disease after Chemo

22 58 node+ 100 pt SNBx (60node+) 40 node2 false - Post op Adjuvant 20 residual disease ANC 38 no further disease Chemo+/Hormone 11 not possible Possibly 1 axillary recurrence Sampling or ANC? (5node+) Neo-adjuvant 100 pt (60node+) Chemotherapy SNBx 38 SN+ 5 false 46 SN true - ANC 3 possibly 4 axillary recurrences

23 3 8 A N C Before 100-After 58 ANC?1 axillary relapse Better prognostic information to guide the oncologists p a t i e

24 Conclusions When performed before neoadjuvant chemotherapy SN Bx is characterised by very high identification rates and low false negative rates. Although the procedure is feasible after neoadjuvant chemotherapy, identification rates and false negative rates are poor by comparison As a result, performing SNBx after neoadjuvant exposes a small number of patients to a risk of being left with residual axillary disease when no further cytotoxic therapy will be given to them. As a result of downstaging of the axillary disease by neoadjuvant chemotherapy up to 20% of node positive patients will be staged incorrectly and their prognosis potentially overestimated.