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Breast Cancer Research and Treatment

, Volume 156, Issue 2, pp 271–278 | Cite as

Is ultrasound-guided fine-needle aspiration cytology of adequate value in detecting breast cancer patients with three or more positive axillary lymph nodes?

  • G. M. Kramer
  • M. W. H. Leenders
  • L. J. Schijf
  • H. L. S. Go
  • T. van der Ploeg
  • M. P. van den Tol
  • W. H. Schreurs
Preclinical study

Abstract

This study evaluated the accuracy of ultrasound-guided fine-needle aspiration cytology of the sonographically most suspicious axillary lymph node (US/FNAC) to select early breast cancer patients with three or more tumour-positive axillary lymph nodes. Between 2004 and 2014, a total of 2130 patients with histologically proven early breast cancer were evaluated and treated in the Noordwest Clinics Alkmaar. US/FNAC was performed preoperatively in all these patients. We analysed the results of US/FNAC retrospectively. Pathological axillary node status (sentinel node biopsy and/or axillary lymph node dissection) was used as reference standard. A total of 634 (29.8 %) of 2130 patients had axillary lymph node metastases on final histology. 248 node positive patients (11.6 %) had three or more positive lymph nodes. The accuracy of US/FNAC to detect three or more positive lymph nodes was 89.8 %, sensitivity was 44.8 %, specificity was 95.7 %, PPV was 58.1 %, and NPV was 92.9 %. This study shows a more than adequate accuracy of preoperative US/FNAC to detect three or more positive lymph nodes (89.8 %). However, when US/FNAC was chosen as the only axillary staging method, 6.4 % of all patients (false negative group) would have been undertreated and 3.8 % of all patients (false positive group) would have been overtreated according to the ACOSOG Z0011 criteria.

Keywords

Breast cancer Axilla Ultrasound Fine-needle aspiration cytology FNAC 

Introduction

In the Netherlands, over 13.900 women a year are diagnosed with early breast cancer [1]. In these patients, sentinel node biopsy (SNB) and axillary lymph node dissection (ALND) have been an integral part of staging axillary lymph nodes for years. Despite the fact that the axillary lymph node status is still considered an important prognostic indicator for patients with invasive breast cancer, the optimal management of the axilla is under debate [2]. It has been extensively proven that survival is not affected by completion axillary lymph node dissection (cALND) in patients with negative sentinel nodes. Hence, in sentinel node-negative patients cALND is not performed [3, 4].

Furthermore, results of the randomised clinical ACOSOG Z011 study affirmed that woman with one or two positive sentinel nodes and a clinical T1–T2 tumour undergoing lumpectomy (followed by breast radiation therapy and systemic therapy) do not benefit from cALND in terms of local control, disease-free survival and overall survival [5]. The comparable IBCSG 23-01 trial showed similar results [6]. Therefore, with the increasing effectiveness of systemic treatment, cALND can be avoided in this subgroup of sentinel node-positive breast cancer patients. Therefore, the current Dutch breast cancer guideline recommends omitting cALND in patients with T1–T2 tumours when there is limited nodal involvement present (i.e. micro- or macrometastases in one or two nodes), as long as adjuvant systemic therapy is administered [7]. Patients with extensive nodal involvement (i.e. three or more axillary lymph nodes involved) should still undergo an ALND [7].

Nowadays, even the necessity of a SNB in selected patients is called into question. Consequently, several randomised clinical trials (the SOUND [8], the NCT 01821768 [9] and the BOOG 2013-08 study [10]) are very recently initiated. These randomised clinical trials study the need for a SNB in early breast cancer patients with negative ultrasound-guided fine-needle aspiration cytology of the sonographically most suspicious axillary lymph node (US/FNAC). Hence, these studies presume an adequate reliability of US/FNAC to differentiate between limited and extensive nodal involvement.

The accuracy of US/FNAC to detect one or more positive axillary lymph nodes has been extensively studied, with sensitivities ranging from 6 to 63 % [11, 12]. Because of these results, routine US/FNAC in the case of early breast cancer is advocated by the UK National Institute of Care and Health Excellence [13] and the current Dutch breast cancer guidelines [7]. This is not the case in the National Comprehensive Cancer Network (NCCN) guideline on breast cancer [14].

However, accuracy of US/FNAC to differentiate between limited (one or two positive lymph nodes) and extensive nodal involvement (three or more positive lymph nodes) is not extensively studied [15, 16]. Therefore, the aim of this study is to investigate the accuracy of preoperative US/FNAC to detect three or more positive axillary lymph nodes.

Patients and methods

A retrospective analysis of a prospectively maintained histopathological database created in the Noordwest Clinics Alkmaar was used to obtain descriptive analyses.

Patients

All patients with breast cancer who presented to the department of surgery in Noordwest Clinics Alkmaar, The Netherlands, between January 2004 and December 2014 were reviewed. Patients were excluded in case of in situ malignancy, neoadjuvant chemotherapy, evidence of breast cancer recurrence or when medical records were not available. Furthermore, patients were excluded if no axillary US or if no SNB or ALND was performed.

Axillary ultrasound and fine-needle aspiration cytology

Conform the Dutch Breast Cancer Guidelines [7], in all breast cancer patients an ipsilateral axillary ultrasound with subsequent FNAC of the sonographically most suspicious lymph node (US/FNAC) was performed. According to the criteria by Van Deurloo et al., FNAC was indicated when a lymph node with a minimum cortex thickness of 2.3 mm, focal cortical thickening or a replaced or anomalous hilum were found [17]. In the present study, the FNAC of this sonographically most suspicious lymph node was used to predict axillary nodal disease (one or more positive lymph nodes) and to predict extensive (three or more positive lymph nodes).

In the Noordwest Clinics Alkmaar, trained breast radiologist and radiology residents under supervision performed the US/FNAC using a 21 Gauge needle. In this study, cytology was defined as benign when, according to international guidelines, specimens were categorised as C1 (insufficient/inadequate), C2 (benign/inflammatory) or C3 (atypical/benign). Cytology was defined as malignant in case of a C4 (suspicious) or C5 (malignant) outcome [14, 18].

Final reference standard/nodal burden quantification

Histological outcome (SNB and/or ALND) was used for definitive axillary staging (reference standard). If no suspicious axillary lymph nodes were found using US or US/FNAC, a standard SNB was performed. An ALND (Berg levels I and II) [19] was performed in case of positive US/FNAC or in case of positive SNB (either micro- or macrometastases). Isolated tumour cells (single tumour cells or cluster of tumour cells not more than 0.2 mm in greatest extent) were classified as node negative. In the multidisciplinary meeting, ALND was chosen over SNB in several specific cases (e.g. multifocal tumours, large primary tumours).

Lymph node ratio

The Lymph node ratio (LNR), defined as the ratio of tumour-positive axillary lymph nodes to the total number of lymph nodes dissected, was calculated for all patients.

Clinicopathological features

The following pathological features of the primary breast tumour were recorded: histology, multifocality, size of tumour (diameter), Bloom & Richardson grade (BR grade), oestrogen receptor status (ER), progesterone receptor status (PR), human epidermal growth factor receptor type 2 (Her2neu) status and mitotic activity index (MAI). In addition, the following clinical features were recorded: age, site of the primary breast tumour and rank of the radiologist performing US/FNAC.

Application of ACOSOG Z0011 criteria

All patients were examined to assess suitability for inclusion as proposed by the ACOSOG Z0011 [5] study group. Any patient with clinical T1-T2 breast carcinoma was selected. Patients undergoing neoadjuvant therapy or with evidence of breast cancer recurrence were excluded in advance. In contrast to ACOSOG Z0011 study group, for our patient population all types of surgery were eligible. Patients undergoing a mastectomy were not ineligible, because the type of operation does not influence the accuracy of preoperative axillary staging (the aim of this study).

Statistical analysis

A Chi-square test (x 2) was done to test if there were significant differences in patient characteristics as age, tumour size, total number of positive lymph nodes, LNR and total number of macro- or micrometastases between several US/FNAC positive and negative groups. The results were analysed with descriptive statistical methods. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated by comparing the results of US, US/FNAC and FNAC alone with final histological findings (SNB and/or ALND). The accuracy of US/FNAC to detect one or more positive lymph nodes was calculated. Furthermore, the accuracy of US/FNAC to detect three or more positive lymph nodes was calculated. Next, clinicopathological features were compared between patients with limited and patients with extensive nodal involvement using univariate and multivariate logistic regression analysis. Differences were considered statistically significant at P < 0.05. Statistical analysis was performed using SPSS 22 for Mac (SPSS Inc. Chicago, IL, USA).

Results

Patient and tumour characteristics

Between 2004 and 2014, a total of 2555 patients were diagnosed with early breast cancer. A total of 253 patients were treated with neoadjuvant chemotherapy. No information concerning lymph node status was available in 52 patients. In 120 patients with a positive SNB, no cALND was performed (because of age, comorbidity, axillary radiotherapy or when multidisciplinary consultation did not indicate further axillary treatment). These patients were excluded as well. Therefore, in total, 425 patients were excluded. Bilateral breast carcinomas (in 41 patients) were considered as independent observations. This resulted in 2130 breast cancer patients eligible for analysis.

Median age was 60 years (range, 26–91 years). Mean primary breast cancer tumour size was 19.0 mm (range; 1–130 mm) and tumour characteristics showed 1713 patients with ductal carcinomas, 288 lobular carcinomas, 36 mixed carcinomas and 93 other carcinomas (tubular, medullar, mucinous, papillary and cribriform carcinomas). Table 1 shows detailed patient and tumour characteristics.
Table 1

Baseline patient and tumour characteristics in 2130 patients with primary invasive breast cancer

Patients characteristics

Mean age (years, range)

60

26–91

 

n

%

 

 Side

   

  Right

1022

48.0

Total: 2130

  Left

1108

52.0

 

 Type

  Ductal

1713

80.4

 

  Lobular

288

13.5

Total: 2130

  Mixed

36

1.7

 

  Other

93

4.4

 

 Grade (Bloom and Richardson)

  I

546

25.6

 

  II

819

38.5

Missing:7

  III

724

34.0

Total: 2123

  Unknown

41

1.9

 

 Size (mean, range) in mm

19

1–130

 

 Size

   

  T1

1409

66.2

Missing:7

  T2

664

31.2

Total: 2123

  T3

50

2.3

 

 ACOSOG-Z0011 group

2073

97.4

 

Axillary nodal burden

Definitive histological outcome (SNB and/or ALND) showed axillary lymph node metastases in 634 patients (29.8 %). 270 patients (12.7 %) had 1, 116 (5, 4 %) patients had 2 and 60 (2.8 %) patients had 3 tumour-positive lymph nodes. 188 (8.9 %) patients had 4 or more positive lymph nodes.

Accuracy of US, US/FNAC and FNAC alone to detect 1 or more positive lymph nodes

The sensitivity of axillary US to detect one or more positive lymph nodes was 47.5 %, specificity was 83.5 %, PPV was 55.1 % and NPV was 78.9 %. The accuracy was 72.8 %. The sensitivity of US/FNAC in detecting one or more positive lymph nodes was 29.7 %, specificity was 99.9 %, PPV was 99.0 % and NPV was 76.9 %. The accuracy was 78.9 %. The sensitivity of FNAC alone in detecting one or more positive lymph nodes was 62.2 %, specificity was 98.0 %, PPV was 99.0 % and NPV was 68.0 %. The accuracy was 78.5 % (Table 2).
Table 2

Correlation axillary ultrasound, ultrasound-guided FNAC and final histological diagnosis. ≥1 versus 0

     

SNB and or ALND

≥1 pos LN

0 pos LN

Total

Ultrasound

Suspiciousa

FNAC

Malignant

 

189

2

191

   

Benign

 

113

241

354

   

No FNAC

 

0

3

3

    

Total

334

1248

1582

     

336

1494

2130

FNAC fine-needle aspiration cytology, SNB sentinel node biopsy, ALND axillary lymph node dissection, Pos positive, LN lymph node

aLymph nodes with cortex thickness of 2.3 mm or larger and lymph nodes with focal cortical thickening

Accuracy of US, US/FNAC and FNAC alone to detect three or more positive lymph nodes

Sensitivity of axillary US to detect three or more positive lymph nodes (i.e. extensive nodal involvement) was 63.3 %. Thus, US was positive in 63.3 % of patients with extensive nodal involvement. Specificity was 79.2 %. Thus, US was negative in 79.2 % of patients without extensive nodal involvement. PPV was 28.6 % and NPV was 94.2 %. Total accuracy of US was 77.3 %. The combination of US followed by FNAC of the sonographically most suspicious lymph node (US/FNAC) was positive in 44.8 % of patients with extensive nodal involvement. Thus, sensitivity of US/FNAC to detect three or more positive lymph nodes is 44.8 %. Specificity of US/FNAC was 95.7 %, PPV was 58.1 % and NPV was 92.9 %. The accuracy was 89.8 %. The sensitivity of FNAC alone in detecting three or more positive lymph nodes was 70.7 %, specificity was 79.5 %, PPV was 58.1 % and NPV was 87.1 %. The accuracy was 77.0 % (Table 3).
Table 3

Correlation axillary ultrasound, ultrasound-guided FNAC and final histological diagnosis. ≥3 versus <3

     

SNB and or ALND

≥3 pos LN

<3 pos LN

Total

Ultrasound

Suspiciousa

FNAC

Malignant

 

111

80

191

   

Benign

 

46

311

357

 

Benign

   

91

1491

1582

    

Total

248

1882

2130

FNAC fine-needle aspiration cytology, SNB sentinel node biopsy, ALND axillary lymph node dissection, Pos positive, LN lymph node

aLymph nodes with cortex thickness of 2.3 mm or larger and lymph nodes with focal cortical thickening

Accuracy of US, US/FNAC and FNAC alone to detect three or more positive lymph nodes in patients who met the inclusion criteria of the ACOSOG Z0011 study

In total, 2073 patients (97.4 %) were eligible according to the criteria applied in the ACOSOG Z0011 study. The sensitivity of axillary US to detect extensive nodal involvement in the ACOSOG Z011 group was 64.3 %, specificity was 79.3 %, PPV was 27.0 % and NPV was 94.9 %. The accuracy was 77.7 %. The sensitivity of US/FNAC to detect extensive nodal involvement in the ACOSOG Z011 group was 44.7 %, specificity was 95.7 %, PPV was 55.6 % and NPV was 93.6 %. The accuracy was 90.3 %. The sensitivity of FNAC alone to detect extensive nodal involvement in the ACOSOG Z011 group was 69.7 %, specificity was 79.4 %, PPV was 55.6 % and NPV was 87.6 %. The accuracy was 76.8 % (Table 4).
Table 4

Correlation axillary ultrasound, ultrasound-guided FNAC and final histological diagnosis in patients selected based on the ACOSOG Z0011 study criteria

ACASOG Z0011a

    

SNB and or ALND

     

≥3 pos LN

<3 pos LN

Total

Ultrasound

Suspiciousb

FNAC

Malignant

 

99

79

178

   

Benign

 

43

304

347

 

Benign

   

79

1469

1548

    

Total

221

1852

2073

FNAC fine-needle aspiration cytology, SNB sentinel node biopsy, ALND axillary lymph node dissection, Pos positive, LN lymph node

aACOSOG Z0011 criteria: Tumour <50 mm (T1–T2), no neoadjuvant therapy, in all patients US and FNAC

bLymph nodes with cortex thickness of 2.3 mm or larger and lymph nodes with focal cortical thickening

Predictors of three or more lymph node metastases

Final histologic diagnosis (SNB and/or ALND) demonstrated three or more positive lymph nodes in 248 (11.7 %) early breast cancer patients. Univariate analyses revealed a significant association between three or more positive lymph nodes with age in general, age <60 versus ≥60 years, breast tumour type, multifocality, B&R Grade 1, tumour diameter, ER, PR and MAI. The multivariate analysis demonstrated multifocality, tumour diameter and PR to be independent predictors of three or more positive lymph nodes (Table 5).
Table 5

Association between clinicopathological factors and occurrence of ≥3 positive lymph nodes. Univariate and multivariate logistic regression

 

Univariate

P value

OR

95 % CI

Logistic regression

    

Age

 

0.09

0.99

[0.98–1.00]

<60 versus ≥60

 

0.02

0.72

[0.55–0.95]

Tumour type

Ductal

0.02

1.00

Lobular

0.04

2.83

[1.03–7.78]

Mixed

0.00

4.12

[1.44–11.79]

Various

0.03

4.45

[1.18–16.84]

Multifocality

1

0.00

1.00

2

0.00

0.28

[0.13–0.62]

3

0.04

0.38

[0.15–0.95]

BR

Grade 1

0.00

1.00

Grade 2

0.29

0.56

[0.19–1.66]

Grade 3

0.74

1.20

[0.42–3.44]

Grade 4

0.26

1.82

[0.64–5.20]

Diameter

 

0.00

1.07

[1.05–1.08]

ER

 

0.02

0.67

[0.48–0.94]

PR

 

0.00

0.62

[0.47–0.83]

Her2Neu

   

[0.79–2.23]

MAI

   

[0.98–6.07]

Radiologist

Radiology resident

0.50

1.00

Radiologist

0.27

0.69

[0.35–1.34]

Breast radiologist

0.58

0.92

[0.68–1.24]

 

Multivariate

P value

OR

95 % CI

Multifocality

1

0.02

1

2

0.01

0.28

[0.11–0.76]

Diameter

 

0.00

1.06

[1.05–1.08]

PR

 

0.01

0.55

[0.35–0.87]

B&R Bloom and Richardson, ER oestrogen receptor, PR progesterone receptor, MAI mitotic activity index, OR odds ratio, 95 % CI confidence interval

P value, univariate P < 0.2, multivariate P < 0.05

Differences in tumour and lymph node characteristics according to the outcome of US/FNAC

Mean tumour diameter was 19.0 mm in all patients. The mean tumour diameter was 21.6 mm in the US−/SNB+ group, 23.2 mm in the US+/FNAC−/SNB+ group and 28.4 mm in the US+/FNAC+ group (P < 0.05). The mean LNR was 0.08 in all patients. LNR was 0.18 in the US−/SNB+ group, 0.19 in the US+/FNAC−/SNB+ group and 0.36 in the US+/FNAC+ group (P < 0.05). Next, the mean number of positive lymph nodes was significantly different between these groups. The mean number of positive lymph nodes was 2.3 in the US−/SNB+ group, 2.7 in the US+/FNAC−/SNB+ group and 5.5 in the US+/FNAC+ group (P < 0.05). Finally, the portion of positive lymph nodes that contain macrometastases is different between these groups, that is 53.9 % in the US−/SNB+ group, 61.7 % in the US+/FNAC−/SNB+ group and 86.5 % in the US+/FNAC+ group (P < 0.05).

Influence on treatment

When omitting SNB and relying on US/FNAC only to detect extensive nodal involvement, in 137 of 2130 patients (6.4 %) US/FNAC is negative whilst definitive histological staging shows three or more positive lymph nodes (false negative group). As a consequence, these patients would be withdrawn from accurate axillary treatment. In contrast, in 80 of 2130 patients (3.8 %) US/FNAC is positive whilst definitive histological staging shows less than three positive lymph nodes (false positive group). Despite the fact that these patients have lymph node metastases (in less than three nodes), these patients are overtreated by a cALND or axillary radiotherapy and are therefore exposed to possible unnecessary complications. Thus, in total 217 of 2130 patients (10.2 %) get incorrect treatment when omitting SNB and relying on US/FNAC only to detect extensive nodal involvement.

Discussion

Recent literature indicates less invasive axillary treatment and questions the role of SNB in clinically lymph node negative breast cancer patients, because the a priori risk of extensive nodal disease (three or more positive lymph nodes) is small. In our opinion, SNB can safely be omitted only if preoperative US/FNAC can reliably differentiate between limited and extensive nodal involvement. Therefore, the diagnostic role of preoperative US/FNAC increases significantly.

Recently, several randomised clinical trials (the SOUND [8], NCT 01821768 [9] and the BOOG 2013-08 [10]) are initiated, randomising early breast cancer patients between SNB and no SNB after negative US/FNAC. Hence, these studies require that the diagnostic role of US/FNAC in detecting extensive nodal involvement is clarified even more. Therefore, we examined the accuracy of US/FNAC extensively in this study, that is to our knowledge the largest available, with 2130 evaluated axillae.

In our study, we demonstrate an accuracy of US/FNAC to detect three or more positive lymph nodes of 89.8 %. Sensitivity to detect three or more positive nodes was 44.8 %, specificity 95.7 %, PPV 58.1 % and NPV 92.9 %. This is in agreement with previous studies regarding differentiation between one or two and three or more (<3 and ≥3) positive axillary lymph nodes. The recent meta-analysis by ‘van Wely et al’ (including 532 US+/biopsy+ patients and 248 US+/biopsy−/SNB+ patients) shows that 56 % of the patients with positive US/FNAC have three or more positive axillary lymph nodes [20]. In comparison, our study shows almost identical numbers, with a PPV of 58 %. This implicates high sensitivity of US/FNAC in predicting extensive axillary nodal involvement. An earlier study by ‘Van Wely et al’ showed an US/FNAC accuracy to detect three or more positive lymph nodes of 90.4 %. The sensitivity, specificity, PPV and NPV were 89.0, 100, 100 and 54 %, respectively, in predicting the extent of axillary node involvement [21]. The difference in the proportion of patients with three or more positive nodes between US+/FNAC−/SNB+ and US−/SNB+ patients was not statistical significant. Similar studies performed by ‘Castellano et al’ and ‘Stefano et al’ demonstrated a sensitivity, specificity, PPV and NPV of 83.7, 100, 100 and 74.6 % [22] and 72.6, 95.7, 96.6 and 67.2 %, respectively [12]. In addition, a study by ‘Reyna et al’ examined the accuracy of US/FNAC detecting three or more positive axillary lymph nodes in 139 axillae. They showed a sensitivity, specificity, PPV and NPV of 90.9, 95.4, 71.4 and 98.8 % [23].

More importantly, US/FNAC was falsely negative in 6.4 % of all patients (US/FNAC was negative whilst definitive histological outcome showed ≥3 positive lymph nodes). These patients would have been undertreated (according to ACOSOG Z0011 criteria) if one had relied on US/FNAC as an axillary staging method solely. In our study, 46 of 357 (12.9 %) patients in the US+/FNAC−/SNB+ group finally had three or more positive lymph nodes. In the US−/SNB+ group, 91 of 1582 (5.8 %) patients had three or more positive lymph nodes on final pathological outcome. Thus, in total, 7.1 % (137 of 1939) of patients with a negative US/FNAC did have three or more positive lymph nodes. Other authors have called the probability of extensive nodal involvement in patients with a negative US/FNAC “low” [21]. However, in our opinion, this chance of 7.1 % is not low, certainly not when one realises that this is a patient population with extensive nodal involvement and therefore poor prognosis. Especially, these patients probably benefit most from additional axillary treatment.

In this study, we found a false positivity of 3.8 %, which implies overtreatment in patients and does not satisfy the aimed conservative approach. This demonstrates that 10.2 % of all patients would have been assigned incorrect treatment when preoperative US/FNAC was chosen as the only axillary staging method, since 6.4 % of US/FNAC results were false negative and 3.8 % were false positive.

Along with the accuracy of US/FNAC, this study looked at the ability of US/FNAC to differentiate prognostic poor outcome patient groups. In this context, next to extensive nodal involvement, the LNR is known as a strong prognostic factor [21, 24].

In our study, the LNR shows a significant worse outcome of 0.36 in US+/FNAC+ group compared to the other groups, 0.18 in US−/SNB+ and 0.19 in US+/FNAC−/SNB+. This could strengthen the argument to omit SNB in US+/FNAC− and US− patients.

Not only the LNR and the mean number of positive lymph nodes are significantly worse in US+/FNAC+ patients, we also showed that portions of positive lymph nodes containing macrometastases are significantly higher in US+/FNAC+ patients compared to the other US/FNAC groups. This is probably a logical result, regarding the fact that radiological suspicion of metastasis is a sign of macrometastases, because macrometastases cause macroscopic changes to the lymph node and hence can be visualised easier by ultrasonography [25].

According to our knowledge, this cohort study is, with 2130 axillae analysed, the most extensive study on this subject. A disadvantage of this study is the retrospective design. This will undoubtedly have led to bias. A prospective design could possibly improve our results. In addition, we considered inadequate FNAC as negative for the purpose of data analysis what obviously influences success rates.

In conclusion, this study shows a more than adequate accuracy of US/FNAC to detect extensive nodal involvement in the axilla (i.e. three or more positive lymph nodes). In our cohort, only 10.2 % of patients would have been treated incorrect when preoperative US/FNAC was chosen as the only axillary staging method (6.4 % undertreatment and 3.8 % overtreatment). However, the question still highly remains whether this accuracy of US/FNAC to detect three or more positive lymph nodes is considered precise enough to plead for a solitary role of preoperative US/FNAC in axillary staging.

Notes

Funding

None.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict.

Ethical approval

This study was conducted according to the principles of the declaration of Helsinki (2008) and in accordance with the Medical Research Involving Human Subjects Act (Dutch: WMO).

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • G. M. Kramer
    • 1
  • M. W. H. Leenders
    • 1
  • L. J. Schijf
    • 2
  • H. L. S. Go
    • 2
  • T. van der Ploeg
    • 3
  • M. P. van den Tol
    • 4
  • W. H. Schreurs
    • 1
  1. 1.Department of SurgeryNoordwest Clinics AlkmaarAlkmaarThe Netherlands
  2. 2.Department of RadiologyNoordwest Clinics AlkmaarAlkmaarThe Netherlands
  3. 3.Department of StatisticsNoordwest Clinics AlkmaarAlkmaarThe Netherlands
  4. 4.Department of SurgeryVU Medical CentreAmsterdamThe Netherlands

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