Ultrasound or FNA for Predicting Node Positive in Breast Cancer Chiun Sheng Huang, MD, PhD, MPH Professor and Chairman Department of Surgery Director of Breast Care Center National Taiwan University Hospital National Taiwan University College of Medicine 1
SLNB has replaced ALND for axillary staging for patient without clinically palpable node 2014 ASCO Guideline of SLNB Recommendation 1: Clinicians should not recommend ALND for women with early stage breast cancer who do not have positive sentinel nodes. 2
Before Z0011: Preoperative Ultrasound can Detect LN Metastasis and Save Patients from SLND van Rijk ASO 2006 Ultrasound suspicious 176 (24%) 732 axillae FNAC positive 59 (34%) FNAC negative 117 (66%) LN-positive 58 (98%) LN-negative 1 (2%) false+ SLN positive 36 (31%) SLN negative 81 (69%) Ultrasound not suspicious 556 (76%) SLN-positive 177 (32%) SLN-negative 379 (68%)
Comparison of diagnostic performance of US and US FNA in diagnosis of axillary lymph node metastasis US only (%) Adding US FNAB (%) p value Sensitivity 73/129 (56.3) 51/129 (39.5) <0.0001 Specificity 205/253 (81.0) 242/253 (95.7) <0.0001 Specificity a 205/243 (84.4) 242/243 (99.6) <0.0001 PPV 73/121 (60.3) 51/62 (82.3) <0.0001 PPV a 73/111 (65.8) 51/52(98.1) 0.0009 NPV 205/261 (78.5) 242/320 (75.6) 0.0296 a Excluding complete responders to chemotherapy ASO 2011: 741
US-guided Sampling of Axillary LNs in Breast Cancer Authors Number of axillae FNAC/ CNB Number (%) of axillae with positive LN Number (%) diagnosed preoperatively Sampling criteria Damera 166 CNB/FNA 64(39%) 27(42%) Suspicious node, FNA if core not feasible % of SLNB avoided 16% Abe et al. 1 144 CNB 80 (56%) 64 (64%) suspicious node, one 44% 185 87(47%) Single node dekanter 17% Et al. 2 FNAC 31 (17%) regardless of echo pattern,69 cases LN visible Deurloo et al. 3 268 FNAC 93 (35%) 37(31%) suspicious node, one 14% Van Riijk et al 4 732 FNAC 271 58 (21%) All suspicious nodes 8% Cilisson et al 5 195 FNAC 93(48%) 52 (56%) All suspicious nodes 27% Damera Br J Cancer 2003, 1.Radiology 2009:41, 2. Br J Surg 1999:1459, 3. EuJ Cancer 2003:1068, 4. ASO 2006; 13;31, 5. Eu J Surg Oncol 2008:497
University Hospital of North Staffordshire, UK 52/142 (37%) cases were LN meta, 51(36%) had abnormal axilla ultrasound Ultrasound sensitivity for lobular ca. was 36% versus 76% for all other The most significant factor producing discordance between preoperative ultrasound and final LN meta was tumor type (p< 0.0019) The Breast Journal, Volume 19 Number 1, 2013 49 55
cortex fatty hilum
US benign Thickened Cortex
Ultrasound Features of Axillary Nodes and Results of Ultrasound Guided Needle Localization Surgical Results, No. (%) of Cases Needle Localized Node to Node Based SLND/ALND Analysis Positive (n=41) Negative (n=150) Positive (n=54) Negative (n=137) Cortical thickness of 1.5 mm 1 (2) 42 (98) 3 (7) 40 (93) 1.5 < cortical thickness 2.5 mm 5 (6) 75 (94) 11 (14) 69 (86) 2.5 < cortical thickness 3.5 mm 19 (40) 29 (60) 23 (48) 25 (52) Cortical thickness of > 3.5 mm and intact fatty hilum Cortical thickness of > 3.5 mm and loss of fatty hilum 7 (70) 3 (30) 7 (70) 3 (30) 9 (90) 1 (10) 10 (100) 0 (0) Cho et. al. AJR 2009:1731
Correlations between Ultrasound and CNB Findings in 144 Patients Abe et al. Radiology 2009:41 CNB Finding* US Finding Malignant Benign Sensitivity Specificity PPV NPV Cortical thickening 63 23 79 (63/80) 64 (41/64) 7(63/86) 71 (41/58) Absence of fatty hilum 26 2 33 (26/80) 97 (62/64) 93(26/28) 53 (62/116) NHBF 52 15 65 (52/80) 77 (49/64) 78 (52/67) 64 (49/77) Cortical thickening and NHBF combined 52 12 65 (52/80) 81 (52/64) 81 (52/64) 65 (52/80) NHBF: Non-hilar blood flow * Data are numbers of lymph nodes (same as numbers of patients). Data are percentages, with the numbers of patients used to calculate the percentages in parentheses. NPV=negative predictive value, PPV=positive predictive value. P<0.001 for all correlations between US and histopathologic findings at X2 testing.
Ultrasound lymph node features of high risk for axillary metastases Br J Radiol. 2008 Aug; 81(968):630-6. cortex thickness indicative of 1-3 N(+) absence of fatty hilum, abnormal lymph node shape and increased peripheral blood flow: indicative of >3 N+ US benign US suspicious US positive
2014 ASCO Guideline of SLNB Recommendation 2.1: Z0011 Clinicians should not recommend ALND for women with early breast cancer who have one or two sentinel lymph node metastases and will receive BCS with conventionally fractionated whole breast radiotherapy and systemic therapy 13
Can US/FNA positive patients undergo BCS and SLNB? Data are insufficient to address whether FNApositive patients can undergo SLNB (under the assumption that resected SLNs represent the FNAbiopsied node) and then avoid ALND after resection of the metastatic SLN. ASCO guideline: Clinicians may still perform SLNB if the abnormal lymph node is removed.
Institute of Oncology Ljubljana, Slovenia 658 patients s/p SLN Ultrasound ( ) Clinically ( ) SLN positive 40%(114/286), 32% if ITC excluded Non SLN positive 23% (18/79 ALND) 9.2% if all had ALND LN (+) no. (mean) 1.7 (median) 1 39% (144/372) 45% (43/96) 3.2 2 Breast Cancer Res Treat. 2006 Jun;97(3):293-9.
Positive Axillary Ultrasound does not exclude the chance of 1 or 2 positive sentinel nodes 1573 Patients of National Taiwan Uni. Hospital Ultrasound Number of Total Positive Lymph Nodes 0 1-3 >3 Total Positive/ Suspicious Negative / Slightly suspicious 128 133 74 335 38.2% 39.7% 22.1% 100% 958 256 24 1238 77.4% 20.7% 1.9% 100% Total 1086 389 98 1573 Fisher's Exact Test: p < 0.0001 16
2014 ASCO Guideline of SLNB Recommendation 2.2: Clinicians may offer ALND for women with early stage breast cancer with nodal metastases found on SNB who will receive mastectomy. IBCSG 23 01: No difference in 5 year DFS between SLNB alone vs. ALND if SLN had micrometastasis Omitting ALND in Mastectomy patients? (9% of patients in each arm)
AUS benign (n=1115) SLN detection failure(n=16) NTUH Patients receiving BCS (n=606) or Mastectomy (n=509) SLN( )(n=883) (80.3%) SLN detection success(n=1099 SLN micrometastasis (n=48) ) (100%) (4.4%) ALND not done (BCs 22, mastec. 8) ALND done Non SLN( )(n=14) 77.8% ALND done Non SLN(+)(n=4) 22.2% SLN macrometastasis (n=168) (15.3%) ALND not done(n=55) ALND done Non SLN( )(n=83) 73.5% ALND done Non SLN(+)(n=30) 26.5%
Ultrasound/FNA for Axillary Staging in Different Scenarios When mastectomy is planned- preoperative ultrasound can detect axillary LN metastasis and save patients from SLND When breast-preserving surgery is planned- if US LN(+) but LN not palpable, SLND is still feasible. However, if the US features favor more than 3 positive nodes, ALND can be considered. And when US LN(-), 19
When axillary ultrasound is negative. the chance of having negative sentinel node is about 77%, and the chance of having more than two or three positive nodes is low For people who still have doubt in Z0011, it is probably safe to follow Z0011 when US is negative. It is not necessary to do intraoperative examination of sentinel node for breast conserving surgery The chance of needing radiation therapy after mastectomy is low. Immediate reconstruction after mastectomy can be planned. 20
Ultrasound/FNA for Axillary Staging in Different Scenarios When mastectomy is planned- preoperative ultrasound can detect axillary LN metastasis and save patients from SLND When breast-preserving surgery is planned- SLND is still feasible if US LN(+) but LN not palpable. However, if the US characteristics favor more than 3 positive nodes, ALND can be considered. And when US LN(-) When neoadjuvant therapy is planned - 21
2014 ASCO Guideline of SLNB SLNB may be offered before or after neoadjuvant systemic therapy (NACT), but the procedure seems less accurate after NACT. Ultrasound is helpful in determining the sequence of SLNB and neoadjuvant chemotherapy (NAC) US LN( ): SLND before or after NAC US LN(+): NAC first, then surgery and SLNB/ALND 22
SLND before Neoadjuvant Chemotherapy If the information of lymph node status is needed before neoadjuvant chemotherapy (NAC) If SLN is negative, or even with two positive SLNs and breast-preserving surgery planned (as in Z0011 trial), before NAC, there is no need to repeat axillary staging after NAC While if SLN is positive before neoadjuvant (more than 2 SLNs in breast-preserving surgery), repeating SLNB after chemotherapy may not be reliable (SENTINA study: FNR 52%) and ALND should be considered after chemotherapy. (SLN will be positive in about 20-25% of patients who have negative axillary ultrasound) 23
SLND after Neoadjuvant Chemotherapy NC could convert 30 to 40 % of node(+) to node(-) SLND done after NC in patients with positive node at diagnosis may save patients from ALND It is good to know whether there is axillary pcr, as axillary pcr is associated with good prognosis (even more prognostic than tumor pcr or not, as demonstrated in a study of 403 patients with preoperative confirmed nodal metastasis. Hennessy JCO 2005:9304 ) Identification rate of SLN after NC is 72-100% 24
SLNB after Neoadjuvant Chemotherapy in Node-Positive Patients IDR False Negative Rate Tracer Tracer SLN number Post CT AUS 2 SLNs removed IHC Single Dual Single Dual 1 2 No Yes No Yes SENTINA 77.4% 87.8% 16.0% 8.6% 24.3% 9.6% (18% if 2SLNs) ACOSOG Z1071 20.3% 10.8% 31.5% 9.1% if 3 SLNs, 21.1% if2 SLNs 12.6 % (N1) 9.8% US(-) SNFNAC 16.0% 5.2% 18.2% 4.9% (with IHC) 13.3% 8.4% IDR: Identification Rate SENTINA Lancet oncology 14(7): 609-618 SNFNAC JCO. 2015 Jan 20;33(3):258-64 ACOSOG Z1071 (Alliance) JAMA. 2013 Oct 9;310(14):1455 61, JCO 2015 doi:10.1200 /JCO.2014.55.7827 25
FNR of SLNB after NAC in patients with positive nodes before NAC NTUH experience Variable Pre NAC LN metastasis No. of Patients No. False Negative FNR 78 19 24.36% SLN number 3 36 4 11.11% 2 22 6 27.27% < 2 20 9 45.00% Change of LN status after NAC positive negative 24 4 16.67% SLN total number 3 13 2 15.38% 2 8 1 12.50% < 2 3 1 33.33%
When Neoadjuvant Chemotherapy (NCT) planned AUS Negative Negative/Positive SLNB NCT (-) (+) AUS NCT NCT Negative Positive ALND (20-25%, Lower if BCS) SLNB with dual tracer ALND - if only one SLN is harvested (20-31% in 3 trials) or any SLN has isolated tumor cells, micrometastasis, macro-metastasis 27 ALND
Sentinel node vs Observation after axillary UltraSouND (SOUND trial ) The Breast 21 (2012) 678-681
Recurrence free survival 0.0 0.2 0.4 0.6 0.8 1.0 Path negative Path positive p=0.793 319 304 286 274 262 243 190 140 107 55 13 62 58 54 52 51 44 32 21 12 9 1 0 6 12 18 24 30 36 42 48 54 60 Time to recurrence/death (months) path=neg path=pos There is no difference in adjuvant treatment decision making and recurrence free survival for patients with true negative and falsenegative AUS Tucker Ann Surg 2016
Thank You