Prognosis of Breast Cancer Patients who
had Sentinel Lymph Node Biopsy alone
after Neoadjuvant Chemotherapy
Hakyoung Kim, Sae Byul Lee, Jisun Kim, Il Yong Chung,
Hee Jeong Kim, Beom Seok Ko, Jong Won Lee,
Sei Hyun Ahn, Byung Ho SonDepartment of Surgery, University of Ulsan College of Medicine
Asan Medical Center, Seoul, Korea
Introduction
• Neoadjuvant chemotherapy(NCT) is being increasingly used to minimize surgery.
• Effect of NCT
• Of node positive patients at disease presentation – 89% had clinical nodal response
– 44% had pathological complete response(pCR)
B. Fisher et al. Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer :
findings from National Surgical Adjuvant Breast and Bowel Project B-18 . J Clin Oncol , 1997
• Accuracy and reliability of sentinel lymph node biopsy(SNB) after NCT– Identification rate : 80.1~ 92.9%
– False negative rate : 8.4~14.2%
Boughey et al. Alliance for Clinical Trials in Oncology.Sentinel lymph node surgery after neoadjuvant chemotherapy in patients
with node-positive breast cancer : the ACOSOG Z1071 clinical trial. JAMA, 2013
KuehnT et al. Sentinel-lymph-node biopsy in patients with breast cancer before and after neoadjuvant chemotherapy(SENTINA):
A prospective, multicentre cohort study. Lancet Oncol .2013
JF Boileau et al. Sentinel Node Biopsy after neoadjuvant chemotherapy in biopsy-proven node-positive breast cancer :
the SN FNAC study. J Clin Oncol, 2015
Introduction• Long term outcome of SNB after NCT
•
• For breast cancer patients who have clinical axillary node conversion from positive to negative following NCT, SNB guided axillary operation is useful strategy.
JY Kang et al. Outcome following sentinel lymph node biopsy-guided decisions in breast cancer patients
with conversion from positive to negative axillary lymph nodes after neoadjuvant chemotherapy. Breast Cancer Res Treat. 2017
Group A (N=428) : SNB guided decision (- : SNB alone / +: ALND)
Group B (N=819) : ALND
P value = 0.148
4 year axillary recurrence rate
A : 2.2%
B : 1.0%
P value = 0.459
Purpose
• Not many studies on long term outcome of SNB in NCT– Optimal extent of axillary surgery of NCT patients is still controversy
• What is axillary recurrence and survival rate of patients who are
– Node positive at disease presentation (cN(+))
– Respond well to NCT
– ONLY OPERATED SNB as axillary surgery
– Is SNB alone acceptable practice ??
Breast Cancer
Stage I-III
NCT
2003-2014
( N=1812 )
SNB alone
( N=760 )
cN(-)
( N=410)
ypN(-)
( N=377 )
3(0.79%)
5 (1.32%)
ypN(+)
( N=33 )
2(6%)
2 (6%)
cN(+)
( N=350 )
ypN(-)
( N= 241 )
5(2.07%)
7 (2.9%)
ypN(+)
( N=109 )
4(3.66%)
7 (6.4%)
No Operation ( N=5 )
SNB+ALND ( N= 593)
ALND ( N= 439)
At Disease
Presentation
(US,MR,FNA,PET)
Median follow up : 54m(5~181)
Good Response to NCT
Axillary recur
Alone 14(1.84%)
Combined 21(2.76%)
At Disease
Presentation
(FNA confirmed)
• SNB procedure
– Radio-isotope colloid injection
– Excision of sentinel lymph node(SLN) and non sentinel lymph node(NSLN).
– Extra sampling of LNs according to surgeon’s decision was allowed
– BUT no ALND
• Mean number of SLN+NSLN (OP record)
– 4.07 (1-10)
Method
Factor N(%)
Age at diagnosis (yrs) <35 114(15.0)
35-50 419(55.1)
>50 227(29.9)
Pre_NG G1 12(1.6)
G2 425(57.2)
G3 306(41.2)
Unknown 17
Pre_HG G1 14(1.9)
G2 429(57.7)
G3 300(40.4)
Unknown 17
Pre_ER Negative 358(47.2)
Positive 401(52.8)
Unknown 1
Pre_PR Negative 448(59.0)
Positive 311(41.0)
Unknown 1
Pre_HER2 (IHC) Negative 537(71.2)
Positive 217(28.8)
Unknown 6
cT stage T1 59(7.8)
T2 558(73.4)
T3 137(18.0)
T4 6(0.8)
cN stage N0 410(53.9)
N1 253(33.3)
N2 25(3.3)
N3 72(9.5)
cStage I 22(2.9)
II 596(78.4)
III 142(18.7)
Op methods BCS 509(67.0)
Mastectomy 251(33.0)
ypT stage T0 154(20.3)
Tis 54(7.1)
T1 350(46.1)
T2 182(23.9)
T3 19(2.5)
T4 1(0.1)
ypN stage N0 615(81.2)
N1 144(18.9)
N2 1(0.1)
pCR No 617(81.2)
Yes 143(18.8)
Table 1. Total characteristic (N = 760)cT stage T1 59(7.8)
T2 558(73.4)
T3 137(18.0)
T4 6(0.8)
cN stage N0 410(53.9)
N1 253(33.3)
N2 25(3.3)
N3 72(9.5)
cStage I 22(2.9)
II 596(78.4)
III 142(18.7)
ypT stage T0 154(20.3)
Tis 54(7.1)
T1 350(46.1)
T2 182(23.9)
T3 19(2.5)
T4 1(0.1)
ypN stage N0 615(81.2)
N1 144(18.9)
N2 1(0.1)
pCR No 617(81.2)
Yes 143(18.8)
Factor
cN(-) cN(+)
P value(N=410) (N=350)
N(%) N(%)Age at diagnosis (yrs) <35 61 (14.9) 54 (15.4) 0.396
35-50 246 (60.0) 194 (55.4)
>50 103 (25.1) 102 (29.2)Nuclear Grade G1 5 (1.3) 7 (2.0) 0.71
G2 229 (57.7) 197 (56.9)
G3 163 (14.1) 142 (41.0)
Unknown 13 4Histologic Graded G1 5 (1.3) 9 (2.6) 0.404
G2 232 (58.4) 198 (57.2)
G3 160 (40.3) 139 (40.2)
Unknown 13 4Estrogen Receptor Negative 202 (49.3) 155 (44.4) 0.182
Positive 208 (50.7) 194 (55.6)
Unknown 0 1Progesteron Receptor Negative 250 (61.0) 197 (56.4) 0.206
Positive 160 (39.0) 152 (43.6)
Unknown 0 1HER2 (IHC) Negative 285 (70.0) 252 (72.6) 0.432
Positive 122 (30.0) 95 (27.4)
Unknown 3 3Operation methods BCO 279 (68.0) 229 (65.4) 0.444
Mastectomy 131 (32.0) 121 (34.6)
Table 2. Characteristic comparing cN(-) and cN(+)
Factor
cN(-) cN(+)
P value(N=410) (N=350)
N(%) N(%)
cT stage T1 19 (4.6) 41 (11.7) <0.001
T2 319 (77.8) 238 (68.0)
T3 71 (17.3) 66 (18.9)
T4 1 (0.2) 5 (1.4)
cN stage N0 410 (100) 0 <0.001
N1 0(0) 252 (72.0)
N2 0(0) 26 (7.4)
N3 0(0) 72 (20.6)
cStage I 21 (5.1) 0 (0) <0.001
II 388 (94.6) 208 (59.4)
III 1 (0.2) 142 (40.6)
ypT stage T0 55 (13.4) 99 (28.3) <0.001
Tis 21 (5.1) 33 (9.4)
T1 192 (46.8) 159 (45.4)
T2 130 (31.7) 51 (14.6)
T3 12 (2.9) 33 (2.2)
T4 0(0) 0(0)
ypN stage N0 377 (92.0) 241 (68.9) <0.001
N1 33 (8.0) 108 (30.9)
N2 0(0) 1 (0.3)
pCR No 357 (87.1) 260 (74.3) <0.001
Yes 53 (12.9) 90 (25.7)
Table 2. Characteristic comparing cN(-) and cN(+)
Result
SNB alone
( N = 760 )
cN (-)
( N = 410 )
ypN (-)
( N = 377 )
ypN (+)
( N = 33 )
cN (+)
( N = 350 )
yp N (-)
( N = 241 )
ypN (+)
( N= 109 )
Result
Fig1. Axillary and Locoregional recurrence free survival of cN(-) vs cN(+)
5 year survival
cN(-) : 98.3%
cN(+) : 96.2 %
5 year survival
cN(-) : 95.4%
cN(+) : 92.0%
5 year recur rate
cN(-) 1.7%
cN(+) 3.8%
Fig2. Distant metastasis free survival and overall survival of cN(-) vs cN(+)
Result
5 year survival
cN(-) : 93.4%
cN(+) : 89.1%
5 year survival
cN(-) : 94.7%
cN(+) : 89.6%
Result
SNB alone
( N = 760 )
cN (-)
( N = 410 )
ypN (-)
( N = 377 )
ypN (+)
( N = 33 )
cN (+)
( N = 350 )
ypN (-)
( N = 241 )
ypN (+)
( N = 109 )
Result
Fig3. Axillary and locoregional recurrence free survival comparing 4 groups
ypN(-)
cN(-)ypN(-) : 0.986
cN(+)ypN(-) : 0.968
ypN(+)
cN(-)ypN(+) : 0.939
cN(+)ypN(+) : 0.913
ypN(-)
cN(-)ypN(-) : 0.961
cN(+)ypN(-) : 0.928
ypN(+)
cN(-)ypN(+) : 0.879
cN(+)ypN(+) : 0.856
Result
Fig4. Distant metastasis free survival and overall survival comparing 4 groups
cN(+)
cN(+)ypN(-) : 0.889
cN(+)ypN(+) : 0.859
cN(-)
cN(-)ypN(+) : 0.970
cN(-)ypN(-) : 0.950
cN(-)
cN(-)ypN(-) : 0.946
cN(-)ypN(+) : 0.936
cN(+)
cN(+)ypN(-) : 0.908
cN(+)ypN(+) : 0.839
cN(+) NCTGood
responseSNB
cN(-) NCTGood
responseSNB
Conclusion
• When NCT response is good
– No significant difference in axillary recurrence free survival
– 5 year axillary recurrence rate : cN(-) : 1.7% cN(+) : 3.8%
– SNB alone is acceptable practice for patients with axillary lymph node positive at
diagnosis and good response to NCT.
• Thank you for your attention
Reason for SNB only in
ypN(+) Group
SNB+Sam
pling, 22,
15%
Negative
in Frozen,
59, 42%
Metastatic
node
removed
with SNB,
61, 43%
n=142 No of Frozen (+) (N=61)
Microinvasion 22
1 34
2 2
No of Frozen(+) (N=22)
Microinvasion 5
1 14
2 3
Excised LN number
Frozen(in OR) Permanant
Total (N=760) 4.06 5.09
cN(-)ypN(-) (N=377) 3.99 4.80
cN(-)ypN(+) (N=33) 4.45 5.21
cN(+)ypN(-) (N=241) 4.09 5.37
cN(+)ypN(+) (N=109) 4.12 5.41
• ACOSCOG Z1071 trial– When at least 2 nodes were removed
– pCR : 41.0% (95% CI, 36.7%-45.3%)
– FNR :12.6 % (90% Bayesian CI, 9.85%-16.05%).Boughey et al. Alliance for Clinical Trials in Oncology.
Sentinel lymph node surgery after neoadujvant chemotherapy in patients with node-positive breast cancer :
the ACOSOG Z1071 clinical trial. JAMA, 2013
• SN FNAC study
– With use of IHC when evaluating sentinel lymph node
– IR : 87.6% (95% CI, 82.2% to 93.0%),
– FNR : 8.4% (95% CI, 2.4% to 14.4%). JF Boileau et al. Sentinel Node Biopsy after neoadjuvant chemotherapy in biopsy-proven node-positive breast
cancer : the SN FNAC study.
J Clin Oncol, 2015
• Z0011
– Median excised node : 2 (1-4)
– 10-yr recurrence rate
• SNB alone : 19.8%
• ALND : 21.8%
• (HR, 0.85 [95% CI, 0.62-1.17]; P = .32).
– Between year 5 and year 10, 1 regional recurrenc
e was seen in the SLND alone group vs none in t
he ALND group. Ten-year regional recurrence did
not differ significantly between the 2 groups.
Result
SNB alone
( N = 760 )
cN (-)
( N = 410 )
ypN (-)
( N = 377 )
ypN (+)
( N = 33 )
cN (+)
( N = 350 )
ypN (-)
( N = 241 )
ypN (+)
( N= 109 )
Fig5. Axillary recurrence free survival and locoregional recurrence free survival of
cN(-)ypN(-) vs cN(+)ypN(-)
Result
cN(-)ypN(-) : 98.6%
cN(+)ypN(-) : 97.1%
cN(-)ypN(-) : 96.0%
cN(+)ypN(-) : 93.7%
Axillary recur : 2.9%
Fig6. Distant metastasis free survival and overall survival of cN(-)ypN(-) vs cN(+)ypN(-)
Result
cN(-)ypN(-) : 92.9%
cN(+)ypN(-) : 90.0%
cN(-)ypN(-) : 94.8%
cN(+)ypN(-) : 90.6%
Discussion for 4 groups
• When compared 4 groups
– Axillary and Locoregional recurrence free
survival
• Lower in pN(+) groups (cN(-)ypN(+), cN(+)ypN(+))
– Distant metastasis free and overall survival
• Lower in cN(+) groups (cN(+)ypN(-), cN(+)ypN(+))