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(+))