Background: Recent clinical trials attempt to determine whether it is appropriate to omit axillary lymph node surgery in patients with cT1–2N0 breast cancer. The study aimed to investigate the true extent of axillary node disease in patients with clinically negative nodes and explore the differences between negative axillary ultrasound (AUS-cN0) and suspicious axillary ultrasound with negative fine-needle aspiration (FNA-cN0). Methods: Pathologically identified T1–2 invasive breast cancer patients with clinically negative nodes were retrospectively analyzed at our center between January 2019 and December 2022. Patients who received any systematic treatment before surgery were excluded from this study. Results: A total of 538 patients were enrolled in this study. 134 (24.9%) patients had pathologically positive nodes, and 404 (75.1%) patients had negative nodes. Univariate analysis revealed that tumor size, T stage, Ki67 level, and vascular invasion (VI) were strongly associated with pathological axillary lymph node positivity. In multivariate analysis, VI was the only independent risk factor for node positivity in patients with cT1–2N0 disease (OR: 3.723, confidence interval [CI]: 2.380–5.824, p < 0.001). Otherwise, pathological node positivity was not significantly different between AUS-cN0 and FNA-cN0 groups (23.4% vs. 28.8%, p = 0.193). However, the rate of high nodal burden (≥3 positive nodes) was significantly higher in FNA-cN0 group. Further investigation revealed that FNA-cN0 and VI were independently associated with a high nodal burden (OR: 2.650, CI: 1.081–6.496, p = 0.033; OR: 3.521, CI: 1.249–9.931, p = 0.017, respectively). Conclusions: cT1–2 breast cancer patients with clinically negative axillary lymph nodes may have pathologically positive lymph nodes and even a high nodal burden. False negatives in AUS and AUS-guided FNA should not be ignored, and sentinel lymph node biopsy remains an ongoing necessity for cT1–2N0 breast cancer patients.

1.
Reimer
T
.
Omission of axillary sentinel lymph node biopsy in early invasive breast cancer
.
Breast
.
2023
;
67
:
124
8
.
2.
Lee
YW
,
Huang
CS
,
Shih
CC
,
Chang
RF
.
Axillary lymph node metastasis status prediction of early-stage breast cancer using convolutional neural networks
.
Comput Biol Med
.
2021
;
130
:
104206
.
3.
Riedel
F
,
Schaefgen
B
,
Sinn
HP
,
Feisst
M
,
Hennigs
A
,
Hug
S
.
Diagnostic accuracy of axillary staging by ultrasound in early breast cancer patients
.
Eur J Radiol
.
2021
;
135
:
109468
.
4.
Sauer
T
,
Kåresen
R
.
The value of preoperative ultrasound guided fine-needle aspiration cytology of radiologically suspicious axillary lymph nodes in breast cancer
.
Cytojournal
.
2014
;
11
:
26
.
5.
Houvenaeghel
G
,
Cohen
M
,
Raro
P
,
De Troyer
J
,
Gimbergues
P
,
Tunon de Lara
C
.
Sentinel node involvement with or without completion axillary lymph node dissection: treatment and pathologic results of randomized SERC trial
.
NPJ Breast Cancer
.
2021
;
7
(
1
):
133
.
6.
Gambardella
C
,
Clarizia
G
,
Patrone
R
,
Offi
C
,
Mauriello
C
,
Romano
R
.
Advanced hemostasis in axillary lymph node dissection for locally advanced breast cancer: new technology devices compared in the prevention of seroma formation
.
BMC Surg
.
2019
18
Suppl 1
125
.
7.
Giuliano
AE
,
Hunt
KK
,
Ballman
KV
,
Beitsch
PD
,
Whitworth
PW
,
Blumencranz
PW
.
Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial
.
JAMA
.
2011
;
305
(
6
):
569
75
.
8.
Giuliano
AE
,
Ballman
KV
,
McCall
L
,
Beitsch
PD
,
Brennan
MB
,
Kelemen
PR
.
Effect of axillary dissection vs No axillary dissection on 10-year overall survival among women with invasive breast cancer and sentinel node metastasis: the ACOSOG Z0011 (alliance) randomized clinical trial
.
JAMA
.
2017
;
318
(
10
):
918
26
.
9.
Hersh
EH
,
King
TA
.
De-escalating axillary surgery in early-stage breast cancer
.
Breast
.
2022
62
Suppl 1
S43
9
.
10.
Magnoni
F
,
Galimberti
V
,
Corso
G
,
Intra
M
,
Sacchini
V
,
Veronesi
P
.
Axillary surgery in breast cancer: an updated historical perspective
.
Semin Oncol
.
2020
;
47
(
6
):
341
52
.
11.
van Roozendaal
LM
,
Vane
MLG
,
van Dalen
T
,
van der Hage
JA
,
Strobbe
LJA
,
Boersma
LJ
.
Clinically node negative breast cancer patients undergoing breast conserving therapy, sentinel lymph node procedure versus follow-up: a dutch randomized controlled multicentre trial (BOOG 2013-08)
.
BMC Cancer
.
2017
;
17
(
1
):
459
.
12.
Araújo
DCM
,
Duarte
GM
,
Jales
RM
,
Shinzato
JY
,
Cardoso Filho
C
,
Torresan
RZ
.
Sentinel lymph node biopsy vs no axillary surgery in early breast cancer clinically and ultrasonographically node negative: a prospective randomized controlled trial-VENUS trial
.
Breast J
.
2020
;
26
(
10
):
2087
9
.
13.
Pulappadi
VP
,
Paul
S
,
Hari
S
,
Dhamija
E
,
Manchanda
S
,
Kataria
K
.
Role of shear wave elastography as an adjunct to axillary ultrasonography in predicting nodal metastasis in breast cancer patients with suspicious nodes
.
Br J Radiol
.
2022
;
95
(
1134
):
20220055
.
14.
Zhu
H
,
Dogan
BE
.
American Joint committee on cancer’s staging system for breast cancer, eighth edition: summary for clinicians
.
Eur J Breast Health
.
2021
;
17
(
3
):
234
8
.
15.
Allison
KH
,
Hammond
MEH
,
Dowsett
M
,
McKernin
SE
,
Carey
LA
,
Fitzgibbons
PL
.
Estrogen and progesterone receptor testing in breast cancer: ASCO/CAP guideline update
.
J Clin Oncol
.
2020
;
38
(
12
):
1346
66
.
16.
Wolff
AC
,
Hammond
MEH
,
Allison
KH
,
Harvey
BE
,
McShane
LM
,
Dowsett
M
.
HER2 testing in breast cancer: American society of clinical oncology/college of American Pathologists clinical practice guideline focused update summary
.
J Oncol Pract
.
2018
;
14
(
7
):
437
41
.
17.
Bartels
SAL
,
Donker
M
,
Poncet
C
,
Sauvé
N
,
Straver
ME
,
van de Velde
CJH
.
Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer: 10-year results of the randomized controlled EORTC 10981-22023 AMAROS trial
.
J Clin Oncol
2022
Jco2201565
.
18.
Keelan
S
,
Heeney
A
,
Downey
E
,
Hegarty
A
,
Roche
T
,
Power
C
.
Breast cancer patients with a negative axillary ultrasound may have clinically significant nodal metastasis
.
Breast Cancer Res Treat
.
2021
;
187
(
2
):
303
10
.
19.
Xiong
J
,
Zuo
W
,
Wu
Y
,
Wang
X
,
Li
W
,
Wang
Q
.
Ultrasonography and clinicopathological features of breast cancer in predicting axillary lymph node metastases
.
BMC Cancer
.
2022
;
22
(
1
):
1155
.
20.
Liang
Y
,
Chen
X
,
Zhan
W
,
Garfield
DH
,
Wu
J
,
Huang
O
.
Can clinically node-negative breast cancer patients with suspicious axillary lymph nodes at ultrasound but negative fine-needle aspiration be approached as having node-negative disease
.
Ann Surg Oncol
.
2017
;
24
(
7
):
1874
80
.
21.
Robbins
T
,
Hoskin
TL
,
Day
CN
,
Mrdutt
MM
,
Hieken
TJ
,
Jakub
JW
.
Node positivity among sonographically suspicious but FNA-negative axillary nodes
.
Ann Surg Oncol
.
2022
;
29
(
10
):
6276
87
.
22.
Naidoo
K
,
Pinder
SE
.
Micro- and macro-metastasis in the axillary lymph node: a review
.
Surgeon
.
2017
;
15
(
2
):
76
82
.
23.
Chen
X
,
He
Y
,
Wang
J
,
Huo
L
,
Fan
Z
,
Li
J
.
Feasibility of using negative ultrasonography results of axillary lymph nodes to predict sentinel lymph node metastasis in breast cancer patients
.
Cancer Med
.
2018
;
7
(
7
):
3066
72
.
24.
Leenders
MW
,
Broeders
M
,
Croese
C
,
Richir
MC
,
Go
HLS
,
Langenhorst
BL
.
Ultrasound and fine needle aspiration cytology of axillary lymph nodes in breast cancer. To do or not to do
.
Breast
.
2012
;
21
(
4
):
578
83
.
25.
Diepstraten
SC
,
Sever
AR
,
Buckens
CF
,
Veldhuis
WB
,
van Dalen
T
,
van den Bosch
MAAJ
.
Value of preoperative ultrasound-guided axillary lymph node biopsy for preventing completion axillary lymph node dissection in breast cancer: a systematic review and meta-analysis
.
Ann Surg Oncol
.
2014
;
21
(
1
):
51
9
.
26.
Groheux
D
,
Hindie
E
.
Breast cancer: initial workup and staging with FDG PET/CT
.
Clin Transl Imaging
.
2021
;
9
(
3
):
221
31
.
27.
Fujii
T
,
Yajima
R
,
Hirakata
T
,
Miyamoto
T
,
Fujisawa
T
,
Tsutsumi
S
.
Impact of the prognostic value of vascular invasion, but not lymphatic invasion, of the primary tumor in patients with breast cancer
.
Anticancer Res
.
2014
;
34
(
3
):
1255
9
.
28.
Hamamoto
Y
,
Ohsumi
S
,
Aogi
K
,
Shinohara
S
,
Nakajima
N
,
Kataoka
M
.
Are there high-risk subgroups for isolated locoregional failure in patients who had T1/2 breast cancer with one to three positive lymph nodes and received mastectomy without radiotherapy
.
Breast Cancer
.
2014
;
21
(
2
):
177
82
.
29.
Wallgren
A
,
Bonetti
M
,
Gelber
RD
,
Goldhirsch
A
,
Castiglione-Gertsch
M
,
Holmberg
SB
.
Risk factors for locoregional recurrence among breast cancer patients: results from international breast cancer study group trials I through VII
.
J Clin Oncol
.
2003
;
21
(
7
):
1205
13
.
30.
Geng
SK
,
Fu
SM
,
Zhang
HW
,
Fu
YP
.
Predictive nomogram based on serum tumor markers and clinicopathological features for stratifying lymph node metastasis in breast cancer
.
BMC Cancer
.
2022
;
22
(
1
):
1328
.
31.
Liu
L
,
Lin
Y
,
Li
G
,
Zhang
L
,
Zhang
X
,
Wu
J
.
A novel nomogram for decision-making assistance on exemption of axillary lymph node dissection in T1-2 breast cancer with only one sentinel lymph node metastasis
.
Front Oncol
.
2022
;
12
:
924298
.
32.
Ouyang
FS
,
Guo
BL
,
Huang
XY
,
Ouyang
LZ
,
Zhou
CR
,
Zhang
R
.
A nomogram for individual prediction of vascular invasion in primary breast cancer
.
Eur J Radiol
.
2019
;
110
:
30
8
.
33.
Cheon
H
,
Kim
HJ
,
Lee
SM
,
Cho
SH
,
Shin
KM
,
Kim
GC
.
Preoperative MRI features associated with lymphovascular invasion in node-negative invasive breast cancer: a propensity-matched analysis
.
J Magn Reson Imaging
.
2017
;
46
(
4
):
1037
44
.
You do not currently have access to this content.