REVIEWS AND COMMENTARY • REVIEW

Axillary Nodal Evaluation in Breast Cancer: State of the Art

Jung Min Chang, MD • Jessica W. T. Leung, MD • Linda Moy, MD • Su Min Ha, MD • Woo Kyung Moon, MD
From the Department of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 03080, Repub-
lic of Korea (J.M.C., S.M.H., W.K.M.); Department of Breast Imaging, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston,
Tex (J.W.T.L.); Department of Radiology, New York University Langone Medical Center, New York, NY (L.M.); NYU Center for Advanced Imaging Innovation and
Research, New York, NY (L.M.). Received November 14, 2019; revision requested December 30; final revision received January 22, 2020; accepted January 24. Address
correspondence to J.M.C. (e-mail: imchangjm@gmail.com).

Conflicts of interest are listed at the end of this article.

Radiology 2020; 295:500–515 • https://doi.org/10.1148/radiol.2020192534 • Content code:

Axillary lymph node (LN) metastasis is the most important predictor of overall recurrence and survival in patients with breast can-
cer, and accurate assessment of axillary LN involvement is an essential component in staging breast cancer. Axillary management in
patients with breast cancer has become much less invasive and individualized with the introduction of sentinel LN biopsy (SLNB).
Emerging evidence indicates that axillary LN dissection may be avoided in selected patients with node-positive as well as node-
negative cancer. Thus, assessment of nodal disease burden to guide multidisciplinary treatment decision making is now considered
to be a critical role of axillary imaging and can be achieved with axillary US, MRI, and US-guided biopsy. For the node-positive
patients treated with neoadjuvant chemotherapy, restaging of the axilla with US and MRI and targeted axillary dissection in addi-
tion to SLNB is highly recommended to minimize the false-negative rate of SLNB. Efforts continue to develop prediction models
that incorporate imaging features to predict nodal disease burden and to select proper candidates for SLNB. As methods of axillary
nodal evaluation evolve, breast radiologists and surgeons must work closely to maximize the potential role of imaging and to pro-
vide the most optimized treatment for patients.
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After reading the article and taking the test, the reader will be able to:
n Describe image findings of axillary lymphadenopathy
n Describe how axillary nodal disease burden can be assessed with US and MRI
n Discuss the role of axillary imaging in selecting a proper candidate for sentinel lymph node biopsy (SNLB) in patients planning upfront surgery versus those planning neoadjuvant chemotherapy treatment
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of this article.

T he presence of axillary lymph node (LN) metastasis and

the number and location of positive LNs determines the
pathologic stage of breast cancer (1,2). LN metastasis is the
of lymphatic drainage, with specific LNs called sentinel
nodes, which drain the breast first, followed by drainage
to the remaining nodal basin. In patients with clinically
most important predictor of overall recurrence and survival node-negative breast cancer, SLNB is the standard surgical
(2). While the 5-year survival rate for patients with disease approach to axillary staging. If the SLNB is negative for
localized to the breast is 98.8%, the figure drops to 85.8% metastases, then no further axillary surgery is required (4).
for patients with regional LN metastases (3). Therefore, ac- Clinical paradigms for axilla treatment have been fur-
curate assessment of axillary LN involvement is an essen- ther changed by the American College of Surgeons
tial component in staging breast cancer and deciding the Oncology Group (ACOSOG) Z0011 trial (6,7) which
appropriate treatment. The nodal status often determines demonstrated that SLNB without ALND is appropriate in
the need for systemic therapy, the extent of surgery, recon- selected patients with clinically node-negative cancer hav-
struction options, and the need for radiation therapy after ing one or two nodal metastases at SLNB and undergoing
mastectomy (4). breast-conserving surgery. The current recommendations
Over the decades, surgical axillary staging and manage- on the use of SLNB for patients with early stage breast
ment in early breast cancer have evolved, becoming less cancer are summarized in Table E1 (online) (8). The role
invasive and more conservative, from complete axillary LN of preoperative axillary US has been challenged after the
dissection (ALND) to sentinel LN biopsy (SLNB) to avoid application of these trial data, since aggressive approach
potential morbidity of uncomfortable postoperative drains with imaging test and percutaneous sampling of axillary
and seroma, pain, neuropathy, limited arm abduction, LNs could preclude SLNB in an otherwise eligible woman
lymphedema, and increased risk of cellulitis (4,5). SLNB is (9). Indeed, some centers have abandoned preoperative
based on the concept that the breast has an orderly pattern axillary US in patients with negative findings on physical
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Abbreviations
ACOSOG = American College of Surgeons Oncology Group, ALND =
axillary lymph node dissection, CI = confidence interval, FNR = false-
negative rate, HER2 = human epidermal growth factor receptor 2,
LN = lymph node, NAC = neoadjuvant chemotherapy, pCR = pathologic
complete response, SLNB = sentinel lymph node biopsy
Summary
Accurate imaging assessment of nodal disease burden in breast cancer
plays an important role in planning initial surgery or neoadjuvant
chemotherapy and guiding axillary management.
Essentials
n In women with newly diagnosed breast cancer, round or irregular
axillary nodes with absent fatty hila or asymmetric cortical thick-
ening are suspicious imaging findings; the number and location of
suspicious nodes and any suspected extranodal extension should
be documented.
n Although US is the primary method for evaluation of axillary
nodes, breast MRI has advantages over US such as improved visu-
alization of the axilla irrespective of patient body habitus and less
operator dependence.
n Assessment of axillary nodal disease burden to guide multidisci-
plinary treatment decision making is now considered to be the
most important role of axillary imaging.
n The incorporation of imaging data in prediction models to deter-
mine axillary nodal disease burden improved model performance
for selecting proper candidates for sentinel lymph node biopsy.
n In patients with biopsy-proven nodal metastasis undergoing neo-
adjuvant chemotherapy, accurate prediction of pathologic com-
plete response and targeted axillary dissection of the biopsy-proven
metastatic node could overcome the problem of high false-negative
rates of sentinel lymph node biopsy.
examination to avoid triaging all women with positive axillary
LN directly to ALND (10). However, physical examination of
the axilla showed a false-negative rate (FNR) that can be as high
as 45% (11), so many centers include US as part of the clinical
examination, defining the term clinically negative as negative at
both physical and US examination. Recent National Compre-
hensive Cancer Network guidelines for breast cancer added axil-
lary assessment with US or other imaging as a routine work-up of
invasive breast cancer. Furthermore, the definition of low tumor
burden, which is image-detected disease not apparent on clinical
examination, was added in the surgical axillary staging section as
a possible candidate of SLNB (12). Additionally, axillary US or
breast MRI is recommended for patients who will undergo neo-
adjuvant chemotherapy (NAC) and in clinically node-negative
patients with presumed pathologic complete response (pCR) af-
ter NAC, so that SLNB rather than ALND may be considered
(13–16) to offer the patient a less-invasive approach (17,18).
Nevertheless, axillary imaging strategies vary among institutions,
ranging from only imaging patients with suspicious findings at
physical examination to imaging all patients with invasive breast
cancer (19). Similarly, large variability exists between surgeons
for clinical axillary management (13).
In this article, we review the most updated evidence for axil-
lary nodal evaluation before treatment and following NAC, fo-
cusing on the roles of axillary imaging to guide axillary manage-
ment for invasive breast cancer, and highlight future directions
Radiology: Volume 295: Number 3—June 2020 n radiology.rsna.org
Chang et al
to improve both efficiency and accuracy of axillary nodal evalua-
tion with use of axillary imaging.
Imaging Modalities for Axillary Nodal Staging
According to the eighth edition of the American Joint Com-
mittee on Cancer staging manual (20), clinical categorization
includes nodes detected with clinical examination or imaging
studies (excluding lymphoscintigraphy). American Joint Com-
mittee on Cancer nodal staging is presented in Table 1. The
definition of clinically suspicious nodes is defined to have one of
following criteria: palpability at physical examination; suspi-
cious imaging features; or proven malignancy at fine-needle as-
piration biopsy, core-needle biopsy, or SLNB. Axillary imaging
should include at least ipsilateral axillary level I (nodes lateral
and inferior to pectoralis minor muscle and includes intrama-
mmary nodes) and II (nodes deep and posterior to pectoralis
minor muscle and includes central and interpectoral nodes).
Imaging or histopathologic evidence of axillary level I or II
lymphadenopathy warrants consideration of imaging level III
axillary (nodes medial and superior to pectoralis minor muscle
and includes infraclavicular nodes), internal mammary, and su-
praclavicular LN involvements (21,22). Axillary US is the pri-
mary imaging tool to assess these sites. However, breast MRI
or chest CT can better demonstrate internal mammary and
supraclavicular LN involvement and provide additional infor-
mation for extensive nodal disease. The anatomy of the axilla
at these imaging modalities has been illustrated in detail previ-
ously (19,23). Schematic diagram of the anatomy of regional
LNs and lymphatic drainage of the breast is shown in Figure 1.
Mammography
Digital mammography or digital breast tomosynthesis is the
first imaging modality recommended for local staging in
women with newly diagnosed breast cancer. Axillary level I
LNs are visible at routine mammography in 50% of patients.
However, axillary visualization is limited and needs special
views to include deep level I or II nodes.
Normal axillary LNs are reniform shaped with thin uniform
cortices and radiolucent fatty hila (Fig 2a), whereas metastatic
nodes show dense obliterated hila and thick cortices with or
without focal bulges (Fig 2b). Microcalcifications in LNs can be
findings of breast cancer metastasis, and often the morphologic
feature of calcification is similar to that of the primary tumor
(Fig 2c) (24). LNs with indistinct or spiculated margins and
perinodal fatty infiltration suggest extranodal extension (Fig 2d)
(25). In women with advanced or inflammatory breast cancer,
diffuse trabecular or skin thickening is often associated with a
high nodal disease burden (26,27).
US Examination
Although the American Joint Committee on Cancer staging
manual does not require imaging studies to assign clinical node
categorization (20), many centers routinely use US for axillary
evaluation in regional staging of breast cancer. Among the vari-
ous modalities, US is the primary method to evaluate the axilla
in women with newly diagnosed breast cancer. One systematic
review found the sensitivity of US to be 49%–87% and the
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Axillary Nodal Evaluation in Breast Cancer
Table 1: Summary of the American Joint Committee on Cancer Nodal Staging
cN Cat-
egory cN Criteria
cNX Regional LN cannot be assessed (eg, previously pNX
removed or no documentation of physical examina-
tion of the axilla)
cN0 No regional LN metastases (by imaging or clinical pN0
examination)
cN1 Metastasis to movable ipsilateral level I, II axillary pN1
LN(s)
cN1mi Micrometastases (approximately 200 cells, larger than pN1mi
0.2 mm, but none larger than 2 mm)
… … pN1a
… …
… …
cN2 Metastases in ipsilateral level I, II axillary LNs that are
clinically fixed or matted; or in ipsilateral internal
mammary nodes in the absence of axillary LNs
metastases
cN2a Metastases in ipsilateral level I, II axillary LNs fixed to
one another (matted) or to other structures
cN2b Metastases only in ipsilateral internal mammary nodes
in the absence of axillary LNs metastases
cN3 Metastases to ipsilateral infraclavicular (level III axil- pN3
lary) LN(s) with or without level I, II axillary LN
involvement; or in ipsilateral internal mammary
nodes with level I, II axillary LN metastases; or
metastases in ipsilateral supraclavicular LN(s) with
or without axillary or internal mammary nodal
involvement
cN3a Metastases to ipsilateral infraclavicular axillary LN(s) pN3a
cN3b Metastases to the ipsilateral internal mammary nodes pN3b
and axillary LN(s)
cN3c Metastases to ipsilateral supraclavicular node(s) pN3c
Note.—After neoadjuvant therapy, ycN and ypN classification are used. Adapted and reprinted, with permission, from Springer Nature,
from reference 20. cN = clinical node, LN = lymph node, pN = pathologic node, SLNB = sentinel lymph node biopsy.
specificity to be 55%–97% when evaluating nonpalpable LNs
based on size alone (28). When based on morphologic crite-
ria, sensitivity was 26%–76% and specificity was 88%–98%
(22,28). The normal axillary LN should be oval and should
have a smooth well-defined margin. The cortex should be
slightly hypoechoic and uniformly thin, measuring 3 mm or
less. Focal cortical bulging or eccentric cortical thickening,
rounded hypoechoic LN, complete or partial effacement of
the fatty hilum, and complete or partial replacement of LN
with an ill-defined or irregular mass are suspicious US findings
suggestive of nodal metastasis (Fig 3) (19,29–34). Whereas
cortical thickening is often associated with reactive nodes, pro-
spective classification of axillary LN cortical thickness in pre-
operative breast cancer patients has shown that the rate of ma-
502
pN Cat-
egory pN Criteria
Regional LN cannot be assessed (eg, not removed for patho-
logic study or previously removed)
No regional LN metastases identified or isolated tumor cells
only
Micrometastses; or metastases in one to three axillary LNs;
and/or clinical negative internal mammary nodes with
micrometastases or macrometastases by SLNB
Micrometastases (approximately 200 cells, larger than 0.2
mm, but none larger than 2 mm)
Metastases in one to three axillary LNs with at least one
node with a deposit greater than 2 mm, at least one
metastasis larger than 2 mm
pN1b Metastases to the ipsilateral internal mammary sentinel
nodes, excluding isolated tumor cells
pN1c pN1a and pN1b combined
pN2 Metastases in four to nine axillary LNs; or positive ipsilat-
eral internal mammary LNs by imaging in the absence of
axillary LN metastases
pN2a Metastases in four to nine axillary LNs, at least one tumor
deposit larger than 2 mm
pN2b Metastases in clinically detected internal mammary nodes
with or without microscopic confirmation; with patho-
logically negative axillary nodes
Metastases in 10 or more axillary LNs; or in infraclavicular
(level III axillary) LNs; or positive internal mammary
node by imaging in the presence of one or more positive
level I, II axillary LNs; or in more than three axillary LNs
and micrometastases or macrometastases by SLNB in
clinically negative ipsilateral internal mammary LNs; or
in ipsilateral supraclavicular LN
Metastases in 10 or more axillary LNs (at least one tumor
deposit larger than 2 mm); or metastases to the infracla-
vicular (level III axillary) LNs
pN1a or pN2a in the presence of cN2b (positive internal
mammary node by imaging)
Metastases in ipsilateral supraclavicular LN
lignancy increased proportionally with cortical thickness (30).
The sonographic features of indistinct margins, node matting,
and perinodal edema predict extranodal extension, which is a
marker of poor prognosis having higher risk of both mortality
and recurrence of disease (33).
To improve the diagnostic performance of US, adjunc-
tive techniques have been investigated. Color Doppler US is
useful for identifying nonhilar peripheral blood flow seen in
metastatic LNs (Fig 4). Diffuse hyperemia arising from the
hilum can also be seen in metastatic LNs, but this finding
can also be seen in reactive LNs (29,35). Malignant LNs had
longer enhancement durations and a greater number of total
and peripheral vessels than did benign LNs before and after
contrast material enhancement on color Doppler US (36,37).
radiology.rsna.org n Radiology: Volume 295: Number 3—June 2020

Figure 1: Schematic diagram shows anatomy of regional
lymph nodes (LNs) and lymphatic drainage of breast. Regional
LNs for breast include axillary, supraclavicular, and internal mam-
mary nodal chains. Axillary LNs are divided into levels I (low
axillary), II (mid axillary), and III (high axillary) in relation with pec-
toralis minor muscle (arrow). Breast lymphatics drain by way of
three major routes: axillary, interpectoral, and internal mammary.
Black oval encircles usual location of sentinel LNs.
In differentiating malignant nodes from benign
nodes, sensitivity of 80% and specificity of 92%
were noted using these variables in logistic re-
gression analysis (36). When elastography was
added to gray-scale US, high stiffness values were
noted in malignant LNs (38,39). Strain elastog-
raphy was found to be more sensitive than was
gray-scale US in depicting abnormal LNs (40);
however, their adjunctive role is still controver-
sial (41,42).
US-guided Needle Biopsy
In addition to morphologic information, US plays an impor-
tant role in guiding biopsies of suspicious nodes. US-guided
fine-needle aspiration biopsy may be performed when adequate
cytology support is available; if not, then core-needle biopsy is
suggested (43). Fine-needle aspiration biopsy is a low-cost and
minimally invasive procedure with high specificity, but there
is a risk of false-negative findings because of potential unders-
ampling (43). In contrast, larger samples can be obtained with
core-needle biopsy with high accuracy and without major com-
plications (29,31,44). Color Doppler US could be used to avoid
large vessels during needle biopsy. A meta-analysis of preopera-
tive US-guided fine-needle aspiration biopsy or core-needle bi-
opsy of axillary nodes in invasive breast cancer showed sensitivity
of 80% (95% confidence interval [CI]: 74%, 84%), specificity
of 98% (95% CI: 97%, 99%), and positive predictive value of
97% (95% CI: 95%, 98%) (45).
Radiology: Volume 295: Number 3—June 2020 n radiology.rsna.org
Chang et al
Figure 2: Images show various mammographic findings of normal and metastatic axillary
lymph nodes (LNs). (a) Right mediolateral oblique (MLO) view from screening mammogram
in a 46-year-old asymptomatic woman demonstrates normal axillary LN (arrow) with oval cir-
cumscribed margin, thin homogeneous cortex, and preserved fatty hilum. (b) Left MLO view in a
72-year-old patient with left invasive ductal carcinoma (IDC) shows dense enlarged level I axillary
LN with hilar obliteration (arrow). Biopsy revealed metastatic adenocarcinoma from breast. (c) Left
MLO view from diagnostic mammogram in a 65-year-old woman with IDC shows level I enlarged
axillary LNs with fine pleomorphic microcalcifications (arrows). Biopsy revealed metastatic adeno-
carcinoma from breast. (Image courtesy of Jung Hyun Yoon, MD, PhD, Department of Radiology,
Severance Hospital, Yonsei University, Seoul, Korea). (d) Right MLO view from diagnostic mam-
mogram in an 81-year-old woman with IDC shows multiple dense enlarged axillary LNs (arrow)
with indistinct margin and fatty infiltration (arrowheads). Axillary LN dissection revealed 16 axillary
LN metastases with extracapsular extension.
Breast MRI
Breast MRI is often performed for breast cancer tumor extent
evaluation, as well as assessing treatment following NAC, and
the axilla is usually included in the field of view. The advantage
of MRI over US is a more global view of the axillae, enhancing
the detection of potentially abnormal LNs and allowing com-
parison of the bilateral axillae irrespective of patient body habitus
(46). Moreover, it is more objective and less operator dependent
than is US (Fig 5). Thus, it should be encouraged to include
axilla during breast MRI evaluation (47).
Markedly enlarged and morphologically abnormal LNs, espe-
cially when distinctly different from other visible axillary nodes,
are highly suggestive of metastasis. Cortical thickening, loss of
fatty hilum, and round shape or a long-to-short axis ratio of less
than 2 are the typical morphologic features that can be seen with
metastasis (19). Moreover, irregular margin, inhomogeneous
cortex, perifocal edema (which is marked prolonged T2 signal
intensity in surrounding soft tissue), and asymmetry of LNs in
503
Axillary Nodal Evaluation in Breast Cancer

high-spatial-resolution axil-
lary T2-weighted MRI showed
high specificity (51). Ultrasmall
superparamagnetic iron oxide
particles have been used as a
contrast agent for LN imaging
in Europe. They accumulate in
macrophages in normal nodes
and cause a signal void due to
magnetic susceptibility effects
of the ferromagnetic iron oxide.
Thus, LNs without signal inten-
sity decrease or uniformly high
signal intensity on ultrasmall su-
perparamagnetic iron oxide–en-
hanced images were considered
metastatic LNs. Ultrasmall su-
perparamagnetic iron oxide–en-
hanced T2*-weighted MRI was
superior to nonenhanced MRI
with a sensitivity of 100% and
a specificity of 95% (52).

Chest CT or PET/CT
Chest CT and PET/CT can
be used to evaluate axillary
nodes in patients with ad-
Figure 3: Images show US findings of normal and metastatic axillary lymph nodes (LNs). (a) US scan in a 45-year- vanced breast disease and
old woman shows normal axillary LN with thin hypoechoic cortex (arrowheads) with central fatty hilum. (b) US image in
showed better diagnostic value
a 51-year-old woman shows biopsy-proven metastatic axillary LN with focal eccentric cortical thickening (arrow). (c) US
image in a 58-year-old woman shows three small but round hypoechoic metastatic axillary LNs; they were confirmed to be for visualizing level III and
metastases at US guided biopsy (arrow). (d) US image in a 47-year-old woman shows biopsy-proven metastatic axillary interpectoral nodes, as well
LN with irregular shape and indistinct margin (arrow) with perinodal extension (arrowheads). as extensive nodal involve-
ment (53). At CT, soft-tissue
masses in axillary, infracla-
vicular, internal mammary, or
supraclavicular regions sug-
gest metastatic LNs in patients
with known breast cancer. A
rounded node, or nodes with
an irregular-appearing or ec-
centrically thickened cortex,
should be considered suspi-
cious (19). At PET, fluorine
18 fluorodeoxyglucose uptake
indicates hypermetabolism
Figure 4: US images demonstrate metastatic lymph node (LN) with invasive ductal carcinoma in a 41-year-old woman.
and can suggest malignant
(a) Grayscale image shows axillary LN with thickened cortex and complete absence of fatty hilum (arrows). (b) Color LN. Chest CT or PET/CT
Doppler image demonstrates increased nonhilar cortical flow (arrow) and diffuse hilar hyperemia (arrowhead) in node. is used for evaluating therapy
response following NAC. In a
terms of number or size compared with the contralateral side are study of 77 patients with breast cancer who underwent three
additional findings suggestive of metastasis (46). Retrospective cycles of NAC, Keam et al (54) reported that patients with
evaluations of axillary LNs with standard breast MRI revealed an axillary LN standard uptake value after NAC greater than
comparable performance to that of US (48). Negative MRI find- 1.5 at PET/CT and an axillary LN size after NAC greater
ings excluded 99.6% and 96% of final pathologic stage of N2- than or equal to 10 mm at CT did not achieve axillary pCR
N3 (pN2-pN3) adenopathy (Table 1) in the non-NAC group (54). PET or PET/CT, however, are neither sufficiently sensi-
and NAC groups, respectively (49). Unenhanced T1 and diffu- tive to detect positive axillary LNs nor sufficiently specific to
sion-weighted MRI showed high accuracy (50), and a dedicated appropriately identify distant metastases (55,56), and the use

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Figure 5: Fat-suppressed contrast material–enhanced T1-
weighted axial MRI scans (repetition time, 5.2 msec; echo time,
2.4 msec; flip angle,12°) in a 69-year-old woman with invasive
ductal carcinoma in right breast show (a) suspicious rim enhanc-
ing level I (arrow) and (b) Rotter (arrowhead) lymph node (LN) in
ipsilateral axilla. A few oval-shaped LNs with thin cortex are noted
in contralateral axilla. This patient was confirmed to have 12
metastatic LNs among 28 removed axillary LNs.
of PET or PET/CT is not indicated in the staging of clinical
stage I, II, or operable stage III breast cancer (12). Among the
seven studies evaluating PET/CT (n = 862), the mean sensi-
tivity was 56% (95% CI: 44%, 67%) and mean specificity
was 96% (95% CI: 90%, 99%) (55).
Pretreatment Axillary Nodal Evaluation
Controversy regarding the Need for Routine Preoperative
Axillary US
The traditional role of preoperative identification of axil-
lary metastases using US and US-guided biopsy is to allow
the surgeon to avoid an unnecessary SLNB and proceed di-
rectly to “fast-track” ALND with its near-perfect specific-
ity and positive predictive value (22,45,57,58). In addition,
preoperative evaluation could potentially help to identify
deep nonpalpable metastatic axillary LNs that may lead to
false-negative SLNB results (30). However, the need for
routine axillary US with or without needle biopsy has been
challenged after the application of the ACOSOG Z0011
trial data to patient treatment (6). The imaging approach
seems clear in patients who do not meet the Z0011 criteria
or have bulky axillary nodal disease burdens where the rec-
ommendation is ALND (12). However, it is controversial
to perform preoperative US in patients who have a single
biopsy-proven metastatic LN but are otherwise eligible for
the Z0011 trial treatment algorithm (Table E2 [online]),
where treatment options may still include SLNB or ALND
(10). There were concerns that imaging tests could triage
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Chang et al
women to unnecessary ALND without SLNB (9), since
even in patients with a positive sentinel LN, 40%–70% had
the sentinel LN as the only site of nodal metastasis (59–61).
In this respect, axillary US could be avoided in patients who
otherwise meet the Z0011 trial criteria. However, the Amer-
ican Society of Breast Surgeons, United Kingdom National
Institute for Health and Care Excellence, and Dutch breast
cancer guidelines still advocate preoperative axillary US in
patients diagnosed with breast cancer (62–64). Thus, axil-
lary US and US-guided biopsy of suspected axillary nodal
metastases should defer to institutional protocols regarding
SLNB.
Assessment and Prediction of Preoperative Axillary Nodal
Disease Burden
With this changing paradigm for axillary surgical manage-
ment, mere identification of nodal metastasis in the axilla by
using imaging is insufficient. If US has the ability to predict
the disease having three or more metastatic LNs, then un-
derestimation of LN staging by using SLNB alone could be
avoided and patients with advanced-stage disease could be
triaged to receive the appropriate adjuvant treatment (65).
Many recent studies aimed to evaluate whether axillary US
or MRI can additionally predict the final axillary nodal dis-
ease burden (66–72) (Table 2). When there are at least two
LNs of high suspicion or a total of three LNs of high and
intermediate suspicion, it is likely that the patient will have
pN2 or higher disease (positive predictive value, 82%) that
should be treated with ALND or NAC (Fig 6) (65). Axil-
lary metastasis proven by using US-guided biopsy also have
significantly more nodal disease burden than do patients with
positive results at SLNB (73). In contrast, SLNB should be
considered when preoperative axillary US is normal, since the
negative predictive value for pN2 and pN3 (Table 1) is 96%,
although the same result was not applicable to the lobular
subtype (32). In another study, the number of abnormal LNs
at axillary US was proportional to the number of metastatic
nodes at final pathologic analysis, and authors suggested that
patients fulfilling Z0011 eligibility criteria with only one
abnormal LN at US should proceed to SLNB (74). The re-
cent National Comprehensive Cancer Network guidelines
for breast cancer updated surgical axillary staging that SLNB
should still be strongly considered in Z0011 patients with
two or fewer abnormal nodes found at imaging, even if one
proved to be positive at biopsy (12). Axillary US should be
considered and used appropriately in the management algo-
rithm of axilla staging (Fig 7).
In addition to assessment of axillary nodal disease burden,
several models have been developed to predict metastasis in-
volving nonsentinel LNs. The most widely used models in-
clude four nomograms (Memorial Sloan Kettering Cancer
Center, Mayo, Cambridge, and Stanford) and three scoring
systems (Tenon, MD Anderson Cancer Center, and Saidi)
(75–81). These models used clinical-pathologic informa-
tion including patient age; mode of tumor detection; tumor
characteristics such as tumor subtype, size, and lymphovas-
cular invasion; multifocality; detection mode of sentinel LN
505
Axillary Nodal Evaluation in Breast Cancer

Table 2: Clinical-Pathologic and Imaging Predictors for Axillary Nodal Disease Burden

Study and Year No. of Women Modality Predictors and Results

Abe et al, 2013 (65) 559 US 2 high suspicious or 3 any combination of high and intermediate suspicious*
LNs at US correlated with 4 metastatic axillary LNs
Caudle et al, 2014 (66)† 708 US Lobular subtype, 3 suspicious axillary LNs at US correlated with 3 metastatic
axillary LNs
Moorman et al, 2014 (67)† 1103 US ,50 years, T2 stage, LVI (positive), multifocality, extracapsular extension, two
macrometastases with SLNB, suspicious axillary US and FNAC (positive) cor-
related with .2 metastatic axillary LNs
Harris et al, 2017 (68)† 129 US Tumor size 2 cm, nonlobular subtype, one positive axillary LN at US correlated
with 3 metastatic axillary LNs
Ahn et al, 2017 (69) 1917 US, CT Younger age, tumor size by preoperative US, CT findings of LN (shortest diam-
eter .1 cm, fatty hila loss, central necrosis), US findings of LN (the grade of
cortical thickness), and US tumor size correlated with 3 metastatic axillary
LNs
Puri et al, 2018 (70)† 123 US Tumor size 2 cm and one positive axillary LN at US correlated with 2 meta-
static axillary LNs
Lim et al, 2018 (71)† 175 US 3 positive axillary LNs at US correlated with 3 metastatic axillary LNs
Kim et al, 2019 (72) 312 US, MRI Tumor size .2 cm, 2 suspicious axillary LNs, cortical thickness 5 mm or fatty
hila loss correlated with 3 metastatic axillary LNs
Note.— Micrometastasis was defined as stage pN1mi; greater than 0.2 mm and less than 2 mm. Macrometastasis was defined as stage
pN1–3; greater than or equal to 2 mm. FNAC = fine-needle aspiration cytology, LN = lymph node, LVI = lymphovascular invasion, SLNB
= sentinel lymph node biopsy.
* LNs of high suspicion have a complete absence or near-complete absence of fatty hila; LNs of intermediate suspicion have a cortical thick-
ness greater than the width of the fatty hila, a cortical thickness of more than 4 mm, a cortical thickness of between 3 mm and 4 mm with
nonhilar blood flow, or asymmetric cortical thickening of more than 3 mm.
†
All patient included in the studies had at least one axillary LN metastasis.

Figure 6: US images in a 75-year-old woman with invasive ductal carcinoma (T2N2M0, estrogen receptor– and progesterone receptor–posi-
tive, human epithelial growth factor receptor 2–negative). (a) Transverse US scan of left breast shows 1.6-cm irregular hypoechoic mass (arrow-
heads) in upper inner quadrant. (b, c) Three suspicious axillary LNs (arrows) were observed in ipsilateral axilla. This patient was confirmed to have
high axillary nodal disease burden, with seven metastatic LNs among 28 removed axillary LNs.

metastasis; number of positive sentinel LNs; and sentinel LN
metastasis size as predictors for nonsentinel LN metastasis.
None of these models used results from imaging studies.
There were several studies that included preoperative axil-
lary US to predict axillary disease burden and non–sentinel LN
metastasis. Ahn et al (69) created a nomogram with preopera-
tive US findings and chest CT of the axilla to predict three or
more axillary LNs in women who met the Z0011 criteria. They
showed that patients with a high probability of having greater
than or equal to three positive axillary LNs can be identified
by using preoperative imaging methods, such as CT and US,
as well as patient demographic and clinical characteristics (69).
Kim et al (82) included preoperative axillary US in addition to
clinical-pathologic characteristics to predict non–sentinel LN
metastasis. Among 1284 patients with no suspicious US find-
ings in axillary LN and clinical T1 stage cancer, 1254 (98%)
did not have non–sentinel LN metastasis. Thus, preoperative
axillary US findings combined with clinical-pathologic infor-
mation can help to select patients at minimal risk of non–sen-
tinel LN metastasis for whom ALND can be omitted.
US features of primary tumor associated with axillary LN
metastasis in patients with clinically node-negative T1–2 breast
cancer have been reported. Shorter skin-to-tumor distance
and tumors with associated architectural distortion at US were

506 radiology.rsna.org n Radiology: Volume 295: Number 3—June 2020

 Chang et al

Figure 7: Flowchart shows axillary staging algorithm recommendation in patients with operable clinical T1–3, N0–1, M0 stage breast cancer. The authors created
this flowchart after extensive review of the literature and the expert opinion and consensus of the authors. Flowchart also reflects current practices in authors’ institutions, and
follows National Comprehensive Cancer guidelines. * = Axillary imaging strategies vary among institutions. † = Image detected disease but clinically not apparent and ap-
pears to be limited in one or two lymph nodes. ‡ = American College of Surgeons Oncology Group Z0011 trial results should be interpreted and applied with caution in
T3 stage breast cancer. ALND = axillary lymph node dissection, FNA = fine-needle aspiration, NAC = neoadjuvant chemotherapy, SLNB = sentinel lymph node biopsy.

important predictors to predict axillary LN metastasis (83). Tu-
mor stiffness at elastography was also associated with axillary LN
metastasis (84,85).
Axillary Nodal Evaluation Following NAC
SLNB in Clinically Node-Positive Cancer Treated with NAC
NAC is increasingly used in both clinically node-negative and
clinically node-positive operable breast cancer to allow more
limited surgery in the breast and axilla (14,86). NAC resulted
in the eradication of axillary LN metastasis in 40% of the pa-
tients. The nodal pCR rate was significantly higher in patients
with triple-negative and human epidermal growth factor recep-
tor 2 (HER2)–positive disease (49% and 65%, respectively)
than in those with hormone receptor–positive, HER2-negative
disease (21%; P , .0001) (87).
The increasing rate of pCR with current chemotherapy regi-
men led to the wider use of SLNB among patients with known
nodal-positive disease and a clinical complete response. A Na-
tional Cancer Database Analysis of 12 965 clinical node-posi-
tive patients undergoing NAC showed higher rates of SLNB,
from 32% in 2012 to 49% in 2015 (P , .001) (88). The main
concerns regarding the use of SLNB are whether the sentinel
LN identification rate is adequate and the FNR is sufficiently
low. In three prospective trials (ACOSOG Z1071, SENTINA
[Sentinel Neoadjuvant], SN FNAC [Sentinel Node Biopsy
Following Neoadjuvant Chemotherapy]), identification rates
were lower with SLNB after NAC (80%–93%) compared
with upfront SLNB (.95%) (17,18,89). The FNRs in the
ACOSOG 1071 and SENTINA trials were 12.6% and 14.2%,
respectively, when at least three sentinel LNs were obtained,
which is higher than the usually accepted FNR of 10% and
deemed clinically unsatisfactory (17,18). False-negative sen-
tinel LNs have significant potential consequences, including
misrepresentation of the prognosis especially for patients with
triple-negative or HER2-positive breast cancer for whom re-
sidual nodal disease signifies a higher likelihood of subsequent
recurrence and death (90,91). In addition, long-term conse-
quences of not resecting LNs with potentially chemotherapy-
resistant disease are unknown (14). A number of efforts are
taken to reduce FNR, including the mandatory use of im-
munohistochemistry (89), retrieval of more than two sentinel
LNs, and using dual-tracer techniques with both blue dye and
radiolabeled colloid mapping agents (17,18,89).
Axillary US with LN Marking for Targeted Axillary
Dissection
To reduce unacceptably high FNR of SLNB, axillary US evalu-
ation after completion of NAC was proposed. After NAC,
morphologic US characteristics of LNs showing oval shape,
normalization of cortical thickness, and isoechoic or hy-
poechoic cortical echogenicity were associated with a higher
probability of pCR (92). In contrast, increased diameter, cor-
tical thickness, and absence of fatty hilum were significantly
associated with residual nodal disease (93). Among the data
recruited for ACOSOG Z1071 trial, 611 axillary US images
after NAC were reviewed. When the criteria of normal axillary
US after NAC was added to SLNB, the FNR reduced from
12.6% to 9.8%. Although this FNR was not statistically signif-
icant (16), the use of axillary US in SLNB showed FNR under
the 10% threshold that is acceptable for clinical care (94). This
study demonstrates that axillary US should be performed pre-
operatively after NAC to optimally identify patients who could
be offered SLNB alone as an alternative to ALND.
Further advances have been made by the researchers on
the hypothesis that removal of biopsy-proven metastatic LNs
should improve diagnostic accuracy of nodal staging after
NAC. In a subset analysis of the ACOSOG Z1071 trial, the

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Axillary Nodal Evaluation in Breast Cancer

Figure 8: Images in a 63-year-old woman with invasive ductal carcinoma (clinical T1N1M0, estrogen receptor– and progesterone receptor–negative, human epi-
thelial growth factor receptor 2–negative). US scan shows clip within biopsy-proven metastatic lymph node (LN) (a) before neoadjuvant chemotherapy (NAC) and (b)
after completion of NAC. Biopsy clip is clearly evident as echogenic structure (arrow). (c) US image shows placement of magnetic seed within clip-containing node. (d)
Specimen radiograph revealed LN with clip (arrow) and magnetic seed (arrowhead). Pathologic examination of clipped axillary node revealed extensive scarring and
was negative for residual viable tumor.

Figure 9: Flowchart shows axillary staging algorithm recommendation in patients planning for neoadjuvant chemotherapy (NAC). The
authors created this flowchart after extensive review of the literature and the expert opinion and consensus of the authors. Flowchart also
reflects current practices in authors’ institutions, and follows National Comprehensive Cancer guidelines. * = If performing fine-needle aspira-
tion (FNA) and able to obtain pathologic results immediately, then may selectively place biopsy clip only in the nodes that are positive for
malignancy. In absence of immediate pathologic results, such as when core biopsy is performed, consider placing clip in all nodes on bi-
opsy. † = Sentinel lymph node biopsy (SLNB) or targeted axillary dissection (TAD) (excision of clipped node, use of dual tracer, and retrieval
of at least two sentinel nodes) can be performed in selected cases when lymph node is negative at imaging and clinically after NAC. ALND
= axillary lymph node dissection.

FNR was reduced to 6.8% (95% CI: 1.9%, 16.5%) when the
metastatic node with clip was retrieved within the sentinel LN
specimen (95). In fact, tumor packing in sentinel LN may lead
to false-negative results and unsuccessful lymphatic mapping
(30). Thus, when the LN is confirmed to be metastatic LN at
US-guided biopsy, a clip should be placed, and removal of the
clipped node could allow detection and targeted removal of
this node. In the Dutch researchers’ work on selective removal
of metastatic LNs after NAC by marking the axillary LN with
radioactive iodine seeds (or MARI procedure), they were able
to correctly identify 65 of 70 patients with residual axillary
tumor activity with FNR of 7% (96). In the MD Anderson
Cancer Center prospective study, the clipped node was not re-
trieved as a sentinel LN in 23% of cases, and targeted axillary
dissection by selectively removing both clipped nodes with sen-
tinel node can reduce the FNR to as low as 2% (97) (Fig 8).
Current National Comprehensive Cancer Network guidelines
state that NAC may allow SLNB alone in selected patients if a
positive axilla resolves with therapy, whereas complete ALND
should be performed if more than two sentinel LNs are not
found or clip-containing node and/or sentinel LN has metas-
tases at frozen-section analysis (12) (Fig 9). Imaging and proce-
dures required for targeted axillary dissection are summarized
in Table 3 (13,98).
Although targeted axillary dissection can reduce FNR of
SLNB, targeted axillary dissection requires a laborious two-
step procedure of clipping the node and preoperatively local-
izing the clipped node, and there are sometimes difficulties in

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Table 3: Imaging and Procedure Steps Required for Targeted
Axillary Dissection
Time Points, Imaging, and Procedures
At time of diagnosis
US identification and documentation of suspicious nodes   
(including location of regional nodal basin, number of abnormal
nodes, and features suggestive of perinodal extension if present)*
US-guided needle biopsy
Placement of US-visible clip under US guidance followed
by    mammogram to confirm clip location
Elective MRI
After completion of NAC
Mammogram and US of breast and nodal basins to deter-
mine   response
Elective MRI
Before surgery
Localization of clipped LN†
Injection of technetium-99m sulfur colloid
During surgery
Injection of peritumoral or subareolar blue dye    intraop-
eratively
Identification of localized clipped metastatic node
Identification of sentinel LN by using gamma probe and
blue    node and determine if clipped node is sentinel LN
Note.—LN = lymph node, NAC = neoadjuvant chemotherapy.
* Suspicious morphologic features at US include cortical thicken-
ing (eccentric or diffuse), loss of normal reniform shape, and loss
of fatty hilum. Features suggestive of perinodal extension include
irregular shape, indistinct margin, and infiltration into the sur-
rounding tissues. Only patients with clinical N1 or N2 disease
are eligible for targeted axillary dissection.
†
With radioactive iodine 125, magnetic seed, radiofrequency tag,
or hookwire.
node visualization at US or in the surgical field after NAC (98).
Marking clips after NAC with wire localization also has many
disadvantages (14). Nonwire localization techniques allow for a
flexible workflow but are not easily accessible due to high costs
(99,100). To solve these problems, radiologic mapping with
unique marker selection (98) or intraoperative US-guided exci-
sion of axillary clips has been suggested (101). Preoperative tat-
tooing with SLNB could be another alternative to clip insertion
for nodal marking because of lower cost and higher convenience
without the use of additional radioactive materials or a local-
ization procedure to ascertain the location of the marker (102).
Ultimately, this technology should evolve to one-step procedure
with long-lasting, safe, efficient, and cost-effective applications
(103). The nonradioactive localizer techniques (104) may indeed
allow for the localizer to be placed at time of biopsy, obviating
the second step of localization after NAC prior to surgery.
Role of Axilla Imaging in Prediction of pCR after NAC
The most favorable outcome regarding low FNR has been
achieved with performing targeted axillary dissection, which
removes metastatic nodes proven by using US-guided biopsy
and sentinel LNs identified separately through suspicious mor-
Radiology: Volume 295: Number 3—June 2020 n radiology.rsna.org
Chang et al
phology and drainage pattern (95,97). However, missing the
metastatic nodes is still possible for the following reasons. First,
deciding which node should be biopsied under US guidance
depends on its size, location, and morphologic features. Second,
only a single LN is biopsied percutaneously among suspicious
nodes and the total number of involved LNs at presentation is
not known. Third, after NAC, the clipped node could be nega-
tive but other nodes could be positive. There remains room for
improving outcomes by combining image information before
and after NAC.
Incorporation of cross-sectional imaging, including chest
CT, PET/CT, and MRI, had been suggested to predict pCR,
because these techniques allow superior visualization of re-
gional LNs located in the apex or outside the axilla and over-
come the limitations of US evaluation, which is often limited
to axillary level I and II. The results showed that pretreat-
ment axillary nodal stage correlated with final surgery results
and survival outcome (105,106). When PET/CT results were
used to triage axillary treatment in combination with the
MARI procedure, unnecessary treatment was reduced in 74%
of the patients (107).
Prediction models that incorporate clinical, pathologic,
and imaging features may aid in selecting proper candidates
for SLNB after NAC. Although they cannot replace current
decision paradigms, they nevertheless allow a more individ-
ualized assessment of axillary pCR. There have been many
efforts to develop nomograms, or scoring systems to pre-
dict axillary pCR, and some of those study results are sum-
marized in Table 4 (108–118). Negative hormone receptor
and positive HER2 receptor status, lower clinical T and N
stages, high histologic and nuclear grade, and breast tumor
response to NAC were the common predictors of axillary
pCR. Interestingly, imaging findings such as tumor size
change at MRI or nodal status at axillary US before or after
treatment were also found to be the important predictors
in many models (Fig 10) (109,111,112,115–118). Accord-
ing to the American College of Radiology Appropriateness
Criteria, the most accurate imaging modality in the assess-
ment of residual disease before and after NAC is MRI for
primary breast cancer and US for axillary LN (119). These
models provide preoperative tools to predict axillary disease
and allow better preoperative planning and patient counsel-
ing regarding appropriate radiation and reconstructive op-
tions (111,113).
Future of Axillary Imaging
As a cost-effective, widely available noninvasive tool, axil-
lary US may preclude the need for axillary surgery in a sub-
group of patients with early disease and nonpalpable axillary
LNs. Several ongoing randomized clinical trials are evaluat-
ing these patients. The SOUND (Sentinel Node versus Ob-
servation after Axillary Ultrasound) (120), INSEMA (In-
tergroup-Sentinel-Mamma) (121), and BOOG 2013–08 (a
Dutch randomized controlled multicenter trial) (122) trials
randomize patients with a negative axillary US to no further
axillary intervention or SLNB, and the SENOMAC (123)
509
Axillary Nodal Evaluation in Breast Cancer

Table 4: Clinical-Pathologic and Imaging Predictors for Axillary pCR

No. of AUC for Estimating Axil-

Study and Year Women Clinical-Pathologic Predictors Imaging Predictors lary pCR
Schipper et al, 2014 (108) 291 Younger age, cT3 or cT4 stage, trastuzumab … 0.77 (0.71, 0.82)
treatment, no taxane treatment, subtype other
than IDC and ILC, ER-negative, HER2-
positive
Kim et al, 2015 (109) 415 Smaller clinical tumor size before and after Higher clinical tumor and 0.82 and 0.80†
NAC, lower pT stage LN response rate*
Jin et al, 2016 (110) 426 ER-negative, HER2-positive, Ki-67 .20% 0.80 and 0.74†
Vila et al, 2016 (111) 584 Lower cT stage, absence of multifocal/multi- No. of abnormal LNs on 0.78 and 0.82†
centric disease, ductal histology, high nuclear US ,4
grade, ER- and PR-negative, HER2-positive
Kim et al, 2017 (112) 201 Higher histologic grade Tumor response rate 0.73 (0.66, 0.80)
47.1%
Murphy et al, 2017 (113) 16 153 ,40 years, cT1 or T2, cN1, poorly differenti- … cN positive: 0.73 and
ated histology, subtype other than IDC and 0.77†cN negative : 0.71
ILC, ER-negative, HER2-positive and 0.74†
Kantor et al, 2018 (114) 13 396 ,50 years, higher tumor grade, ductal histology, … 0.78 and 0.78†
cN1, pCR of breast tumor, ER-negative,
HER2-positive
Ouldamer et al, 2018 116 Premenopausal status, HR-negative Tumor shrinkage 50% 0.78 (0.69, 0.86)
(115) on MRI
Kim et al, 2019 (116) 227 Higher histologic grade, HR-negative 1.5 cm residual tumor 0.78 (0.72, 0.83)
size, no enlarged axillary
LN on US after NAC
Osorio-Silla et al, 2019 150 ER-negative, HER2-positive pCR of breast tumor at 0.79 (0.72, 0.87)
(117) MRI
Kim et al, 2019 (118) 408 Initial cN1, Ki-67 .20%, HR-negative, HER2- Tumor size reduction 0.84 and 0.78†
positive .50%, no enlarged
axillary LNs on US after
NAC
Note.—Data in parentheses are 95% confidence intervals listed in the literature. AUC = area under the curve, cN = clinical node, cT =
clinical tumor, ER = estrogen receptor, HER2 = human epithelial growth factor receptor 2, HR = hormone receptor, IDC = invasive ductal
carcinoma, ILC = invasive lobular carcinoma, LN = lymph node, NAC = neoadjuvant chemotherapy, pCR = pathologic complete response,
PR = progesterone receptor, pT = pathologic tumor.
* Clinical response of breast mass and axillary LN was evaluated with US examination.
†
AUC for validation set was also reported.

trial (Sentinel Node Biopsy in Breast Cancer: Omission of
Axillary Clearance after Macrometastases) expands inclu-
sion criteria to patients undergoing mastectomy. TAXIS
(Tailored Axillary Surgery with or without ALND Followed
by Radiation Therapy in Patients with Clinically Node-
positive Breast Cancer) evaluates survival after selectively
removing positive LNs as a less-extensive surgical option in
patients with clinically node-positive cancer (124). Wider
application of SLNB or even no axillary surgery in early
stage breast cancer will increase the need for more accurate
imaging methods for diagnosis and prediction of axillary
nodal disease preoperatively.
The less invasive and more elegant way of US-guided
biopsy of sentinel LN might be considered in the future
in combination with percutaneous excision and ablation of
the primary breast cancer (125). Preoperative sentinel LN
identification was evaluated by using contrast material–en-
hanced US with intradermal injections of microbubbles
injected in the periareolar area (Fig 11). After the injec-
tion, the contrast medium accumulates in the first draining
LN, and after the enhancing sentinel LN is identified by
using contrast-enhanced US, it can be biopsied under US
guidance (126) (Fig 12). The sentinel LNs without metas-
tasis tend to manifest as homogeneous enhancement, while
metastatic sentinel LNs show heterogeneous or no enhance-
ment. Systematic review and meta-analysis revealed that
for patients with invasive carcinoma, a clinically negative
axilla, and normal axillary US, the sentinel LN identifica-
tion and localization rate by using contrast-enhanced US
was 70%–90%. Preoperative contrast-enhanced US-guided
SLNB showed pooled sensitivity of 54% and pooled speci-
ficity of 100% for identification of nodal metastases (127).
Radiomics and deep learning or artificial intelligence–
based integration of imaging and clinical-pathologic in-
formation promise to improve the accuracy of predict-
ing metastatic LNs in the future. A recently developed

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 Chang et al

Figure 10: Images in a 53-year-old woman with invasive ductal carcinoma (clinical T2N2M0, estrogen receptor– and
progesterone receptor–positive, human epithelial growth factor receptor 2–positive). Before neoadjuvant chemotherapy
(NAC), (a) sagittal maximum intensity projection (MIP) (repetition time msec/echo time msec, 4.5/2.0; flip angle, 12°)
and (b) fat-suppressed contrast material–enhanced T1-weighted axial MRI scan (3.6/1.8; flip angle, 12°) reveal 2.2-cm
enhancing mass in right upper outer breast (arrow, a) and enlarged ipsilateral axillary lymph node (LN) at level I (arrow-
head, b). After NAC, (c) sagittal MIP (4.5/2.0; flip angle, 12°) and (d) fat-suppressed contrast-enhanced T1-weighted
axial MRI (4.0/0; flip angle, 10°). After six cycles of docetaxel, trastuzumab, carboplatin, and pertuzumab treatment, pri-
mary breast cancer shrunk to 0 cm, resulting in (c) complete tumor response without demonstrable lesion on MIP. There was
(d) normalized axillary LN (arrowhead) at MRI after NAC. After total mastectomy and axillary LN dissection, pathologic
examination showed no residual tumor in breast and axilla.

Figure 11: Images in a 65-year-old woman with invasive ductal carcinoma. (a) Photograph of
US contrast agent intradermally injected at periareolar area. (b) US scan. By tracing along courses
of enhanced lymphatic channels (arrows), first enhanced node was deemed as sentinel lymph
node (LN) (arrowhead) with homogeneous enhancement. Sentinel LN biopsy after skin marking of
lymphatic channel and enhanced LN revealed no LN metastasis. (Images courtesy of Qingli Zhu,
MD, Ultrasound Department, Peking Union Medical College Hospital, Beijing, China.)

radiomic nomogram based on MRI features performed well performed moderately in determining the number of meta-
in identifying LN metastasis (area under the curve of 0.84 static LNs (area under the curve of 0.79) (128). By using
and 0.87 in training and validation sets, respectively) and US features of primary breast cancer, deep learning models

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Axillary Nodal Evaluation in Breast Cancer

Figure 12: Images in a 65-year-old woman with invasive ductal carcinoma. (a) Dual mode of contrast material–enhanced
US (left) and gray-scale image (right) clearly show contrast-enhanced lymphatic channel (arrows) with contrast-enhanced sentinel
lymph node (LN) (arrowhead). Gray-scale image shows elliptical-shaped node with effaced fatty hilum (arrowhead). (b) Fine-nee-
dle aspiration was performed in contrast-enhanced LN, which was confirmed to be negative, followed by US-guided dye marking
in same node using indocyanine green (ICG). Subsequently, conventional sentinel LN biopsy was performed with blue dye (patent
blue). One blue-stained sentinel LN was removed and some amount of ICG was observed in this node by the naked eye or was
clearly identified as a fluorescence signal by using near-infrared camera. Final pathologic examination also showed no malignancy
in sentinel LN. (Images courtesy of Kenzo Shimazu, MD, Department of Breast and Endocrine Surgery, Osaka University, Osaka,
Japan.)

were able to predict clinically negative axillary LN metas-
tasis (129,130). In addition, current convolutional neural
network architectures predicted the likelihood of axillary
LN metastasis (131) and NAC treatment response using
a breast MRI data set obtained prior to initiation of NAC
(132). The advent of artificial intelligence and its applica-
tion in medicine will lead to new frontiers in breast cancer
care in an unprecedented fashion. With deep learning, we
may use our collective data and experience in deriving pro-
tocols and algorithms where we may offer treatment tai-
lored to a particular patient to achieve the best outcomes
with the least morbidity and risks. When this principle is
applied to the evaluation and management of nodal dis-
ease, we will be able to reduce the need for surgery and
associated complications including lymphedema and target
appropriate medical and radiation therapy with least ad-
verse effects. At the same time, patient outcomes including
long-term survival will be maximized, and breast cancer
care will be delivered in a cost-effective manner.
Conclusion
In the setting of invasive breast cancer, imaging of the axilla
helps to determine the presence of metastatic disease with
moderate accuracy that is improved with the use of US-
guided biopsy of suspicious nodes. Although staging with
axillary US or MRI cannot replace surgical staging at this
time, imaging still plays an important role in guiding axil-
lary lymph node dissection or sentinel lymph node biopsy
for patients planning initial surgery or neoadjuvant chemo-
therapy. As the trend toward less-aggressive axillary surgery
continues, a more precise yet encompassing role for imag-
ing might be required in staging axillary disease. We must
continue to refine our techniques to provide more accurate
preoperative staging and posttreatment response evaluation
to minimize intervention while seeking to preserve or even
enhance patient outcome.
Acknowledgment: We thank Hyoeun Kim, MArch (adjunct professor at Ewha
Woman’s University) for creating the drawing in Figure 1. We also thank Wonshik
Han, MD; Hyeong-Gon Moon, MD; and Han-Byoel Lee, MD (professors of de-
partment of surgery, Seoul National University Hospital, Seoul, Korea) for their
advice on axillary surgery and treatment.
Disclosures of Conflicts of Interest: J.M.C. disclosed no relevant relationships.
J.W.T.L. Activities related to the present article: disclosed no relevant relationships.
Activities not related to the present article: is a consultant for CureMetrix; received
payment for lectures including service on speakers bureaus from Fuji; holds stock/
stock options in Subtle Imaging. Other relationships: disclosed no relevant relation-
ships. L.M. Activities related to the present article: institution received a grant from
Siemens; is a consultant for Lunit and iCAD; receives support for travel to meetings
for the study or other purposes from Chinese Radiology Society and Society of
Breast Imaging. Activities not related to the present article: disclosed no relevant
relationships. Other relationships: disclosed no relevant relationships. S.M.H. dis-
closed no relevant relationships. W.K.M. disclosed no relevant relationships.
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