Skip to main content

Main menu

  • Home
  • Content
    • Current
    • Ahead of print
    • Past Issues
    • JNM Supplement
    • SNMMI Annual Meeting Abstracts
    • Continuing Education
    • JNM Podcasts
  • Subscriptions
    • Subscribers
    • Institutional and Non-member
    • Rates
    • Journal Claims
    • Corporate & Special Sales
  • Authors
    • Submit to JNM
    • Information for Authors
    • Assignment of Copyright
    • AQARA requirements
  • Info
    • Reviewers
    • Permissions
    • Advertisers
  • About
    • About Us
    • Editorial Board
    • Contact Information
  • More
    • Alerts
    • Feedback
    • Help
    • SNMMI Journals
  • SNMMI
    • JNM
    • JNMT
    • SNMMI Journals
    • SNMMI

User menu

  • Subscribe
  • My alerts
  • Log in
  • Log out
  • My Cart

Search

  • Advanced search
Journal of Nuclear Medicine
  • SNMMI
    • JNM
    • JNMT
    • SNMMI Journals
    • SNMMI
  • Subscribe
  • My alerts
  • Log in
  • Log out
  • My Cart
Journal of Nuclear Medicine

Advanced Search

  • Home
  • Content
    • Current
    • Ahead of print
    • Past Issues
    • JNM Supplement
    • SNMMI Annual Meeting Abstracts
    • Continuing Education
    • JNM Podcasts
  • Subscriptions
    • Subscribers
    • Institutional and Non-member
    • Rates
    • Journal Claims
    • Corporate & Special Sales
  • Authors
    • Submit to JNM
    • Information for Authors
    • Assignment of Copyright
    • AQARA requirements
  • Info
    • Reviewers
    • Permissions
    • Advertisers
  • About
    • About Us
    • Editorial Board
    • Contact Information
  • More
    • Alerts
    • Feedback
    • Help
    • SNMMI Journals
  • View or Listen to JNM Podcast
  • Visit JNM on Facebook
  • Join JNM on LinkedIn
  • Follow JNM on Twitter
  • Subscribe to our RSS feeds
Research ArticleClinical Investigation

Determining the Axillary Nodal Status with 4 Current Imaging Modalities, Including 18F-FDG PET/MRI, in Newly Diagnosed Breast Cancer: A Comparative Study Using Histopathology as the Reference Standard

Janna Morawitz, Nils-Martin Bruckmann, Frederic Dietzel, Tim Ullrich, Ann-Kathrin Bittner, Oliver Hoffmann, Svjetlana Mohrmann, Lena Häberle, Marc Ingenwerth, Lale Umutlu, Wolfgang Peter Fendler, Tanja Fehm, Ken Herrmann, Gerald Antoch, Lino Morris Sawicki and Julian Kirchner
Journal of Nuclear Medicine December 2021, 62 (12) 1677-1683; DOI: https://doi.org/10.2967/jnumed.121.262009
Janna Morawitz
1Department of Diagnostic and Interventional Radiology, University of Dusseldorf, Dusseldorf, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nils-Martin Bruckmann
1Department of Diagnostic and Interventional Radiology, University of Dusseldorf, Dusseldorf, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Frederic Dietzel
1Department of Diagnostic and Interventional Radiology, University of Dusseldorf, Dusseldorf, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tim Ullrich
1Department of Diagnostic and Interventional Radiology, University of Dusseldorf, Dusseldorf, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ann-Kathrin Bittner
2Department of Gynecology and Obstetrics, University Hospital Essen, University of Duisburg–Essen, Essen, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Oliver Hoffmann
2Department of Gynecology and Obstetrics, University Hospital Essen, University of Duisburg–Essen, Essen, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Svjetlana Mohrmann
3Department of Gynecology, University of Dusseldorf, Dusseldorf, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lena Häberle
4Institute of Pathology, Heinrich-Heine-University and University Hospital Duesseldorf, Duesseldorf, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Marc Ingenwerth
5Institute of Pathology, University Hospital Essen, West German Cancer Center, University of Duisburg–Essen and the German Cancer Consortium, Essen, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lale Umutlu
6Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Wolfgang Peter Fendler
7Department of Nuclear Medicine, University of Duisburg-Essen and German Cancer Consortium–University Hospital Essen, Essen, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tanja Fehm
3Department of Gynecology, University of Dusseldorf, Dusseldorf, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ken Herrmann
7Department of Nuclear Medicine, University of Duisburg-Essen and German Cancer Consortium–University Hospital Essen, Essen, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gerald Antoch
1Department of Diagnostic and Interventional Radiology, University of Dusseldorf, Dusseldorf, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lino Morris Sawicki
1Department of Diagnostic and Interventional Radiology, University of Dusseldorf, Dusseldorf, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Julian Kirchner
1Department of Diagnostic and Interventional Radiology, University of Dusseldorf, Dusseldorf, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Visual Abstract

Figure
  • Download figure
  • Open in new tab
  • Download powerpoint

Abstract

The purpose of this study was to compare breast MRI, thoracic MRI, thoracic 18F-FDG PET/MRI, and axillary sonography for the detection of axillary lymph node metastases in women with newly diagnosed breast cancer. Methods: This prospective double-center study included patients with newly diagnosed breast cancer between March 2018 and December 2019. Patients underwent thoracic (18F-FDG PET/)MRI, axillary sonography, and dedicated prone breast MRI. Datasets were evaluated separately regarding nodal status (nodal-positive vs. nodal-negative). Histopathology served as the reference standard in all patients. The diagnostic performance of breast MRI, thoracic MRI, thoracic PET/MRI, and axillary sonography in detecting nodal-positive patients was tested by creating receiver-operating-characteristic curves (ROC) with a calculated area under the curve (AUC). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated for all 4 modalities. A McNemar test was used to assess differences. Results: In total, 112 female patients (mean age, 53.04 ± 12.6 y) were evaluated. Thoracic PET/MRI showed the highest AUC, with a value of 0.892. The AUCs for breast MRI, thoracic MRI, and sonography were 0.782, 0.814, and 0.834, respectively. Differences between thoracic PET/MRI and axillary sonography, thoracic MRI, and breast MRI were statistically significant (PET/MRI vs. axillary sonography, P = 0.01; PET/MRI vs. thoracic MRI, P = 0.02; PET/MRI vs. breast MRI, P = 0.03). PET/MRI showed the highest sensitivity (81.8% [36/44]; 95% CI, 67.29%–91.81%), whereas axillary sonography had the highest specificity (98.5% [65/66]; 95% CI, 91.84%–99.96%). Conclusion: 18F-FDG PET/MRI outperforms axillary sonography, breast MRI, and thoracic MRI in determining the axillary lymph node status. In a clinical setting, the combination of 18F-FDG PET/MRI and axillary sonography might be considered to provide even greater accuracy in diagnosis.

  • breast cancer
  • axillary lymph node metastasis
  • PET/MRI
  • oncologic imaging

Breast cancer is the most common cancer in women worldwide, representing about 25% of all cancers in women (1). Initial treatment strategies and patients’ prognosis are fundamentally based on tumor biology and tumor stage. Typically, the axillary lymph nodes are the first site of nodal metastatic disease in invasive breast cancer (2). The ability to distinguish between nodal-positive and nodal-negative status in both pre- and posttherapeutic situations is crucial to provide an appropriate and individualized therapeutic concept for the axilla and to determine prognosis (3). So far, sentinel lymph node biopsy or sentinel lymph node excision has been regarded as the gold standard for axillary staging in early breast cancer (4), but different surgical axillary procedures such as targeted lymph node excision or targeted axillary dissection have been proposed as favorable alternatives to deescalate invasive procedures such as axillary dissection (5). However, these invasive procedures can cause morbidity such as infection or hematoma, as well as causing patient discomfort. At the time of initial diagnosis, about 25%–40% of early breast cancer stages show axillary nodal metastatic disease (6,7), which means that for about 60%–75% of the patients with early-stage breast cancer any kind of axillary intervention represents overtreatment. Therefore, a noninvasive imaging method for discriminating between nodal-positive and nodal-negative axillary status is desirable to avoid unnecessary biopsies before therapy and to facilitate therapy planning.

Different imaging modalities are available for the initial staging of breast cancer patients. Over the last few years, breast MRI, axillary sonography, and CT have become well established in this regard (8,9). However, no imaging modality has yet proven accurate enough to replace invasive procedures for determining the correct nodal status (10,11). While 18F-FDG PET imaging can reliably display increased glycolytic activity in metastatic tissue, MRI offers images with high anatomic resolution and high soft-tissue contrast. Hence, hybrid 18F-FDG PET/MRI might serve as an excellent combined imaging modality for locoregional staging compared with conventional imaging such as ultrasound, breast MRI, or CT (12).

The aim of our study was to compare thoracic 18F-FDG PET/MRI, breast MRI, thoracic MRI, and axillary sonography with regard to their ability to determine the correct axillary nodal status in patients with primary breast cancer, using histopathology as the reference standard.

MATERIALS AND METHODS

Patients

The local ethics committees approved this prospective, double-center study (studies 17-7396-BO and 6040R). All patients gave written informed consent before enrolment. Patients who had newly diagnosed, therapy-naive breast cancer with an elevated risk for distant metastases between March 2018 and December 2019 were included in this study if they fulfilled the following criteria: a newly diagnosed, treatment-naïve T2 or higher tumor; a newly diagnosed, treatment-naïve triple-negative tumor of any size; or a newly diagnosed, treatment-naïve tumor with molecular high risk (Ki-67 > 14% or G3 or her2 overexpression). Breast feeding, pregnancy, malignancies in the last 5 y, or contraindications to MRI or MRI contrast agents were exclusion criteria. Of the 112 patients, 45 had been reported previously (13). In contrast to the prior publication, we investigated further imaging modalities such as breast MRI and sonography for axillary nodal staging instead of the comparison of MRI, PET/MRI, and bone scintigraphy for N and M staging.

PET/MRI and Breast MRI

All 18F-FDG PET/MRI examinations were performed from head to mid thigh on an integrated 3.0-T PET/MRI scanner (Biograph mMR; Siemens Healthcare GmbH) with the patient supine, about 60 min after intravenous injection of a body weight–adapted dose of 18F-FDG (4 MBq/kg of body weight). Patients fasted for 6 h before the examination, and blood glucose levels were ensured to be below 150 mg/dL before 18F-FDG was injected.

Just before the whole-body imaging was performed, each patient underwent dedicated breast MRI in the head-first prone position on the same integrated 3.0-T PET/MRI scanner. The imaging protocol has been detailed by Kirchner et al. (14). Thoracic whole-body PET/MRI and MRI sections were evaluated for axillary nodal status and are referred to here as 18F-FDG thoracic PET/MRI and thoracic MRI.

PET/MR and MR Image Analysis

Images were analyzed independently and in random order by 2 experienced radiologists with extensive experience in hybrid imaging, as well as by a nuclear medicine specialist, using an OsiriX Workstation (Pixmeo SARL) with a reading intermission of 4 wk to avoid recognition bias. Discordant readings were resolved in a collective consensus reading. For every patient and modality, the axillary lymph node status was rated as either nodal-positive or nodal-negative. Morphologic features for the diagnosis of lymph node metastases on MRI were short-axis diameter greater than 10 mm, irregular margin, inhomogeneous cortex, perifocal edema, absence of fatty hilum, asymmetry in comparison to the contralateral site, contrast medium enhancement, and blurred nodal border (15). In PET/MRI, tracer uptake above the level of the direct background and the surrounding lymph nodes was considered a sign of malignancy. To measure SUVmax and SUVmean, a manually drawn region of interest was placed around the respective lymph node. Readers were masked to patient identity, history, and the results of local and distant metastasis but aware of the diagnosis of breast cancer.

Axillary Sonography

Axillary sonography was performed at each center by a gynecologist with multiple years of experience in breast and axillary ultrasound. No regular second assessment was done by a second reader. An Acuson S2000 system (Siemens Healthcare GmbH), a SuperSonic Imagine Aixplorer (Toshiba Medical Systems GmbH), and an Aplio MX SSA-780A system (Toshiba Medical Systems GmbH), each with a linear array transducer of 5–12 MHz, were used. Lymph nodes were regarded as suggestive, mostly with an indication for biopsy, when the cortical thickness was greater than 3 mm, the cortex was lobulated, or the hilum was decreased or absent (16,17).

Reference Standard

Histopathology served as the reference standard in every patient and was used to evaluate the nodal status (nodal-positive vs. nodal-negative). If available, tissue samples from axillary dissection or sentinel lymph node biopsy before systemic therapy were used as the reference standard. If no sufficient pretherapeutic sampling was available, sentinel lymph node excision or axillary dissection after neoadjuvant systemic therapy was used as a surrogate reference standard. In the case of insufficient pretherapeutic sampling, additional histologic preparations were evaluated, using focal fibrosis or focal necrosis as an indirect indication for previously vital lymph node metastases (18,19).

Statistics

Statistical analysis was performed using SPSS Statistics, version 26 (IBM Corp.). A P value of less than 0.05 was considered statistically significant. Data are presented as mean ± SD. The diagnostic performance of breast MRI, thoracic MRI, thoracic PET/MRI, and axillary sonography in detecting nodal-positive patients was tested by creating receiver operating-characteristic (ROC) curves with a calculated area under the curve (AUC). A McNemar test was used to assess AUC differences between thoracic PET/MRI and axillary sonography, thoracic MRI, and breast MRI and between axillary sonography and thoracic MRI, respectively. In addition, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated for breast MRI, thoracic MRI, thoracic PET/MRI, and axillary sonography. Sensitivity was defined as true-positive/(true-positive + false-negative). Specificity was defined as true-negative/(true-negative + false-positive). Positive predictive value was defined as true-positive/(true-positive + false-positive). Negative predictive value was defined as true-negative/(true-negative + false-negative). Accuracy was defined as (true-negative + true-positive)/(true-negative + true-positive + false-negative + false-positive) (20). To compare SUVmax between false-positive and correctly positive lymph nodes on thoracic PET/MRI, a Student t test was used.

RESULTS

Patient Population and Reference Standard

In total, 112 women (mean age, 53.04 ± 12.6 y) were prospectively included in this study (Fig. 1). Patient demographics and primary tumor characteristics are presented in Table 1. In every patient, breast MRI, thoracic MRI, and PET/MRI were available. Axillary sonography was available in 108 patients. In all patients, 18F-FDG was used as the tracer (mean activity, 247.7 ± 53.52 MBq).

FIGURE 1.
  • Download figure
  • Open in new tab
  • Download powerpoint
FIGURE 1.

STARD diagram showing initial number of patients and reasons for exclusion.

View this table:
  • View inline
  • View popup
TABLE 1

Patient Demographics and Primary Tumor Characteristics

On the basis of the reference standard, 44 patients (39%) were nodal-positive, whereas 68 (61%) patients were nodal-negative. In 57 of 112 patients, histologic samples were taken before systemic therapy (31 axillary core-needle biopsies, 20 sentinel lymph node excisions, and 6 axillary dissections), whereas 55 samples were taken right after neoadjuvant systemic therapy (50 sentinel lymph node excisions and 5 axillary dissections).

Diagnostic Performance

Of the imaging modalities tested, thoracic PET/MRI showed the highest AUC, with a value of 0.892 (95% CI, 0.801–0.953) (Fig. 2; Table 2). The AUCs for breast MRI, thoracic MRI, and axillary sonography were 0.782 (95% CI, 0.674–0.871), 0.814 (95% CI, 0.718–0.904), and 0.834 (95% CI, 0.740–0.920), respectively.

FIGURE 2.
  • Download figure
  • Open in new tab
  • Download powerpoint
FIGURE 2.

Receiver-operating-characteristic curves for diagnostic performance, comparing axillary lymph node positivity among thoracic PET/MRI, axillary sonography, thoracic MRI, and breast MRI.

View this table:
  • View inline
  • View popup
TABLE 2

AUC for the 4 Modalities

We found that PET/MRI had the highest sensitivity of the 4 imaging modalities (81.8% [36/44]; 95% CI, 67.29%–91.81%), whereas breast MRI had the lowest sensitivity (61.4% [27/44]; 95% CI, 45.50%–75.64%). On the other hand, axillary sonography had the highest specificity (98.5% [65/66]; 95% CI, 91.84%–99.96%), whereas breast MRI and thoracic PET/MRI had the lowest specificity (each 95.6% [65/68]; 95% CI, 87.64%–99.08%). At 96.7% (29/30; 95% CI, 80.39%–99.51%), axillary sonography had the best positive predictive value, whereas breast MRI showed the weakest positive predictive value (90.0% [27/30]; 95% CI, 74.37%–96.54%). Thoracic PET/MRI offered the best negative predictive value, at 89.0% (65/73; 95% CI, 81.25%– 93.84%). In contrast, breast MRI offered the weakest negative predictive value (79.3% [65/82]; 95% CI, 72.42%– 84.77%). Overall, thoracic PET/MRI showed the best diagnostic accuracy (90.18% [101/112]; 95% CI, 83.11%– 94.99%) (Tables 3 and 4; Figs. 3 and 4). Differences between PET/MRI and axillary sonography (P = 0.01), thoracic MRI (P = 0.02), and breast MRI (P = 0.03) were statistically significant, whereas differences between axillary sonography and thoracic MRI were not (P = 0.68).

FIGURE 3.
  • Download figure
  • Open in new tab
  • Download powerpoint
FIGURE 3.

Pathologically confirmed axillary lymph node metastasis (arrows) that was correctly identified on 18F-FDG PET/MRI (A) because its tracer uptake was above background level (SUVmax, 4.7). This lymph node was rated false-negative on axillary sonography (B), thoracic MRI (C), and breast MRI (D).

FIGURE 4.
  • Download figure
  • Open in new tab
  • Download powerpoint
FIGURE 4.

Pathologically confirmed axillary lymph node metastasis (arrows) that was correctly identified on 18F-FDG PET/MRI (A) because its tracer uptake was above background level (SUVmax, 4.3). It was also identified on axillary sonography (B) because of its cortical enlargement to 3.8 mm (short-axis diameter, 8 mm). This lymph node was rated nonsuggestive on thoracic MRI (C) and breast MRI (C). Large primary is seen in right breast.

View this table:
  • View inline
  • View popup
TABLE 3

Correct and False-Positive, as Well as Correct and False-Negative, Findings for the 4 Modalities

View this table:
  • View inline
  • View popup
TABLE 4

Sensitivity, Specificity, Positive Predictive Value, Negative Predictive Value, and Accuracy for the 4 Modalities

According to the reference standard, 8 of 44 nodal-positive patients (18.2%) were missed on thoracic PET/MRI; these patients were rated false-negative by the other 3 imaging modalities as well. Four of these patients received primarily operative therapy. The latency time between imaging and histopathologic sampling was 39.25 ± 4.38 d in these 4 patients. The remaining 4 patients received neoadjuvant chemotherapy, and the latency time between imaging and the start of chemotherapy was 18.25 ± 5.54 d.

Axillary sonography showed only one false-positive rating and the highest specificity. This patient was rated false-positive as well in breast MRI, thoracic MRI, and thoracic PET/MRI (Fig. 5). Thoracic PET/MRI showed 3 false-positive ratings, in 2 of which the primary tumor had previously been marked by a clip. These false-positive lymph nodes showed an SUVmax significantly lower than that of the correctly positive lymph nodes (3.73 ± 0.75 with a range of 3.0–4.5, vs. 6.31 ± 3.96 with a range of 2.6–17.7; P = 0.002).

FIGURE 5.
  • Download figure
  • Open in new tab
  • Download powerpoint
FIGURE 5.

Suggestive right axillary lymph node (arrows) seen on all imaging modalities. As no signs of malignancy were seen on histopathology, this lymph node was rated false-positive on all modalities. (A) Thoracic PET/MRI: 9 mm lymph node with loss of fatty hilum, very slight perifocal edema, and 18F-FDG uptake slightly above background level (SUVmax, 3.7). (B) Sonography: hypoechogenic lymph node with loss of fatty hilum (10 mm). (C) Thoracic MRI: 9-mm lymph node with loss of fatty hilum and very slight perifocal edema. (D) Breast MRI: 8-mm lymph node with loss of fatty hilum and contrast agent affinity.

DISCUSSION

In this study, we compared the diagnostic performance of 4 state-of-the-art imaging modalities regarding their ability to determine the axillary nodal status of 112 patients with newly diagnosed breast cancer. The results indicate that thoracic 18F-FDG PET/MRI is superior to thoracic MRI, prone breast MRI, and axillary sonography. While 18F-FDG PET/MRI offers the highest sensitivity, accuracy, and AUC for detecting locoregional lymph node metastases, axillary sonography is the imaging modality with the highest specificity.

Correctly identifying nodal status is crucial in patients with newly diagnosed breast cancer, because it is a major factor in choosing the optimal treatment strategy (21–24). Until some years ago, complete axillary dissection was the standard for axillary staging and at the same time was a procedure to achieve regional control (25). Because various studies have shown sentinel lymph node biopsy to be equal to axillary dissection for staging purposes, sentinel lymph node biopsy or equivalent procedures have evolved as the standard for patients with a clinically low risk of axillary nodal metastases (26–28).

Our results are in line with other studies, as they underscore that breast MRI has a minor role in evaluating the axillary nodal status of breast cancer. This limited role is due mostly to the limited field of view of breast MRI using dedicated breast coils that do not allow a complete assessment of the axillary region. Despite the introduction of more advanced MRI protocols or lymph node–specific contrast agents, the data have remained insufficient from an oncologic perspective (29).

Sonography comes with the advantage of low cost and wide accessibility, but the quality of the examination depends on the skill and experience of the examiner. Our data show axillary ultrasound to have a high specificity (98.5%) but a limited negative predictive value (83.8%). This drawback of axillary ultrasound has also been described by Farrell et al., who reported a high specificity of 100% but a risk of underestimating the number of affected lymph nodes (30).

In our study, 18F-FDG PET/MRI demonstrated the best diagnostic performance in detecting nodal-positive patients, compared with the other modalities (AUC of 0.892). Previous PET/MRI studies in primary breast cancer showed conflicting results regarding nodal staging: whereas Botsikas et al. and Grueneisen et al. found an equal or superior diagnostic performance for MRI alone compared with PET/MRI (31,32), van Nijnatten et al. showed an added value of dedicated axillary PET/MRI compared with MRI alone (33). Further studies even indicated that PET/MRI could lead to treatment changes or could replace invasive sampling, compared with conventional staging with MRI, ultrasound, or full-field digital mammography (12). In our study, 18F-FDG PET/MRI still missed about 18% of the nodal-positive patients while having the best negative predictive value of all imaging modalities (89%), emphasizing its high reliability in excluding malignancy in locoregional lymph nodes.

The highest specificity, on the other hand, was achieved by axillary sonography, which depicted only 1 false-positive finding, whereas PET/MRI lead to 3 false-positive ratings. Two of these 3 false-positive patients had previously undergone clip marking of the primary tumor, pointing to a reactive 18F-FDG uptake in these lymph nodes.

False-positive lymph nodes showed a significantly lower SUVmax than correctly positive lymph nodes. However, because the ranges in SUVmax in the 2 groups overlapped and the number of false-positive lymph nodes was very low, there is no reliable SUVmax cutoff.

There were limitations to this study. Most importantly, some samples were taken after neoadjuvant systemic therapy and therefore had to be evaluated retrospectively, taking into account indirect histopathologic indicators for metastasis such as focal posttherapeutic fibrosis or necrosis (18,19). Furthermore, several samples were taken as a percutaneous biopsy, representing only a part of a lymph node. In contrast to lymph node excision, this sampling method also bears a small residual risk of missing tumor cells. Furthermore, the prospective study design intended axillary sonography to be the first examination, as it was conducted in the same session as breast sonography and histopathologic sampling of the primary tumor to ensure accordance with the patient inclusion criteria. Therefore PET/MRI and MRI examinations were often performed after clip marking of the breast, which may have caused reactive axillary lymphadenopathy. Therefore, the number of false-positive findings in PET/MRI and MRI might be artificially increased.

Our data suggest that 18F-FDG PET/MRI provides the highest overall diagnostic performance, that 18F-FDG PET/MRI should be used to exclude metastatic spread to axillary lymph nodes, and that axillary sonography should be used to confirm the diagnosis of suspected nodal positivity. Consequently, future workflows should consider performing 18F-FDG PET/MRI as a searching tool before clip marking of the primary tumor, if applicable in clinical workflow, and to add axillary sonography afterward to specify findings. If both imaging modalities show a positive nodal status, one might even consider dispensing with axillary histopathologic sampling. Although tissue pathology will be the final determiner of the N stage, knowledge that PET/MRI is more sensitive than the other modalities will help in the growing field of targeted biopsy in the future. However, further prospective studies would be needed to investigate the potential replaceability of sampling by this approach.

CONCLUSION

18F-FDG PET/MRI outperforms axillary sonography, breast MRI, and thoracic MRI in determining the axillary lymph node status. In a clinical setting, the combination of 18F-FDG PET/MRI and axillary sonography might be considered to provide even greater accuracy in diagnosis.

DISCLOSURE

Wolfgang P. Fendler is a consultant for Endocyte and BTG, and he received fees from RadioMedix, Bayer, and Parexel outside the submitted work. The study was funded by the Deutsche Forschungsgemeinschaft (DFG), the German Research Foundation (BU3075/2-1; KI2434/1-2). No other potential conflict of interest relevant to this article was reported.

KEY POINTS

QUESTION: Is the diagnostic performance of thoracic 18F-FDG PET/MRI better than that of thoracic MRI, breast MRI, and axillary sonography?

PERTINENT FINDINGS: Thoracic 18F-FDG PET/MRI showed the highest sensitivity (81.8%) and highest AUC (0.892) in assessing axillary nodal status, whereas axillary sonography was the most specific imaging modality (98.5%).

IMPLICATIONS FOR PATIENT CARE: PET/MRI might be used to exclude axillary metastatic disease, and axillary sonography might be added afterward to specify findings if PET/MRI shows nodal involvement.

Footnotes

  • Published online May 20, 2021.

  • © 2021 by the Society of Nuclear Medicine and Molecular Imaging.

REFERENCES

  1. 1.↵
    Cancer today. International Agency for Research on Cancer website. Breast, Globocan 2020. https://gco.iarc.fr/today/data/factsheets/cancers/20-Breast-fact-sheet.pdf. Accessed October 28, 2021.
  2. 2.↵
    1. Woods RW,
    2. Camp MS,
    3. Durr NJ,
    4. Harvey SC.
    A Review of options for localization of axillary lymph nodes in the treatment of invasive breast cancer. Acad Radiol. 2019;26:805–819.
    OpenUrl
  3. 3.↵
    1. Gandhi A,
    2. Coles C,
    3. Makris A,
    4. et al
    . Axillary surgery following neoadjuvant chemotherapy: multidisciplinary guidance from the Association of Breast Surgery, Faculty of Clinical Oncology of the Royal College of Radiologists, UK Breast Cancer Group, National Coordinating Committee for Breast Pathology and British Society of Breast Radiology. Clin Oncol (R Coll Radiol). 2019;31:664–668.
    OpenUrl
  4. 4.↵
    1. Larson KE,
    2. Valente SA,
    3. Tu C,
    4. Dalton J,
    5. Grobmyer SR.
    Surgeon-associated variationin breast cancer staging with sentinel node biopsy. Surgery. 2018;164:680–686.
    OpenUrl
  5. 5.↵
    1. Simons JM,
    2. van Nijnatten TJA,
    3. van der Pol CC,
    4. Luiten EJT,
    5. Koppert LB,
    6. Smidt ML.
    Diagnostic accuracy of different surgical procedures for axillary staging after neoadjuvant systemic therapy in node-positive breast cancer: a systematic review and meta-analysis. Ann Surg. 2019;269:432–442.
    OpenUrl
  6. 6.↵
    1. Chua B,
    2. Ung O,
    3. Taylor R,
    4. Boyages J.
    Frequency and predictors of axillary lymph node metastases in invasive breast cancer. ANZ J Surg. 2001;71:723–728.
    OpenUrlCrossRefPubMed
  7. 7.↵
    1. Cutuli B,
    2. Velten M,
    3. Martin C.
    Assessment of axillary lymph node involvement in small breast cancer: analysis of 893 cases. Clin Breast Cancer. 2001;2:59–65.
    OpenUrlPubMed
  8. 8.↵
    1. Yang WT.
    Staging of breast cancer with ultrasound. Semin Ultrasound CT MR. 2011;32:331–341.
    OpenUrlCrossRefPubMed
  9. 9.↵
    1. Choi HY,
    2. Park M,
    3. Seo M,
    4. Song E,
    5. Shin SY,
    6. Sohn YM.
    Preoperative axillary lymph node evaluation in breast cancer: current issues and literature review. Ultrasound Q. 2017;33:6–14.
    OpenUrl
  10. 10.↵
    1. Rahbar H,
    2. Partridge SC,
    3. Javid SH,
    4. Lehman CD.
    Imaging axillary lymph nodes in patients with newly diagnosed breast cancer. Curr Probl Diagn Radiol. 2012;41:149–158.
    OpenUrlPubMed
  11. 11.↵
    1. Valente SA,
    2. Levine GM,
    3. Silverstein MJ,
    4. et al
    . Accuracy of predicting axillary lymph node positivity by physical examination, mammography, ultrasonography, and magnetic resonance imaging. Ann Surg Oncol. 2012;19:1825–1830.
    OpenUrlPubMed
  12. 12.↵
    1. Goorts B,
    2. Voo S,
    3. van Nijnatten TJA,
    4. et al
    . Hybrid 18F-FDG PET/MRI might improve locoregional staging of breast cancer patients prior to neoadjuvant chemotherapy. Eur J Nucl Med Mol Imaging. 2017;44:1796–1805.
    OpenUrl
  13. 13.↵
    1. Bruckmann NM,
    2. Sawicki LM,
    3. Kirchner J,
    4. et al
    . Prospective evaluation of whole-body MRI and 18F-FDG PET/MRI in N and M staging of primary breast cancer patients. Eur J Nucl Med Mol Imaging. 2020;47:2816–2825.
    OpenUrl
  14. 14.↵
    1. Kirchner J,
    2. Grueneisen J,
    3. Martin O,
    4. et al
    . Local and whole-body staging in patientswith primary breast cancer: a comparison of one-step to two-step staging utilizing 18F-FDG-PET/MRI. Eur J Nucl Med Mol Imaging. 2018;45:2328–2337.
    OpenUrl
  15. 15.↵
    1. Baltzer PA,
    2. Dietzel M,
    3. Burmeister HP,
    4. et al
    . Application of MR mammography beyond local staging: is there a potential to accurately assess axillary lymph nodes? Evaluation of an extended protocol in an initial prospective study. AJR. 2011;196:W641–W647.
    OpenUrlCrossRefPubMed
  16. 16.↵
    1. Cho N,
    2. Moon WK,
    3. Han W,
    4. Park IA,
    5. Cho J,
    6. Noh DY.
    Preoperative sonographic classification of axillary lymph nodes in patients with breast cancer: node-to-node correlation with surgical histology and sentinel node biopsy results. AJR. 2009;193:1731–1737.
    OpenUrlCrossRefPubMed
  17. 17.↵
    1. Bedi DG,
    2. Krishnamurthy R,
    3. Krishnamurthy S,
    4. et al
    . Cortical morphologic features of axillary lymph nodes as a predictor of metastasis in breast cancer: in vitro sonographic study. AJR. 2008;191:646–652.
    OpenUrlCrossRefPubMed
  18. 18.↵
    1. Takahashi Y,
    2. Soh J,
    3. Shien K,
    4. et al
    . Fibrosis or necrosis in resected lymph node indicate metastasis before chemoradiotherapy in lung cancer patients. Anticancer Res. 2020;40:4419–4423.
    OpenUrlAbstract/FREE Full Text
  19. 19.↵
    1. Newman LA,
    2. Pernick NL,
    3. Adsay V,
    4. et al
    . Histopathologic evidence of tumor regression in the axillary lymph nodes of patients treated with preoperative chemotherapy correlates with breast cancer outcome. Ann Surg Oncol. 2003;10:734–739.
    OpenUrlCrossRefPubMed
  20. 20.↵
    1. Parikh R,
    2. Mathai A,
    3. Parikh S,
    4. Chandra Sekhar G,
    5. Thomas R.
    Understanding and using sensitivity, specificity and predictive values. Indian J Ophthalmol. 2008;56:45–50.
    OpenUrlCrossRefPubMed
  21. 21.↵
    1. Donegan WL.
    Tumor-related prognostic factors for breast cancer. CA Cancer J Clin. 1997;47:28–51.
    OpenUrlCrossRefPubMed
  22. 22.
    1. Neri A,
    2. Marrelli D,
    3. Roviello F,
    4. et al
    . Prognostic value of extracapsular extension of axillary lymph node metastases in T1 to T3 breast cancer. Ann Surg Oncol. 2005;12:246–253.
    OpenUrlCrossRefPubMed
  23. 23.
    1. Danko ME,
    2. Bennett KM,
    3. Zhai J,
    4. Marks JR,
    5. Olson JA Jr.
    . Improved staging in node-positive breast cancer patients using lymph node ratio: results in 1,788 patients with long-term follow-up. J Am Coll Surg. 2010;210:797–805.e1, 805–807.
    OpenUrl
  24. 24.↵
    1. Rosen PR,
    2. Groshen S,
    3. Saigo PE,
    4. Kinne DW,
    5. Hellman S.
    A long-term follow-up study of survival in stage I (T1N0M0) and stage II (T1N1M0) breast carcinoma. J Clin Oncol. 1989;7:355–366.
    OpenUrlAbstract
  25. 25.↵
    1. Rao R,
    2. Euhus D,
    3. Mayo HG,
    4. Balch C.
    Axillary node interventions in breast cancer: a systematic review. JAMA. 2013;310:1385–1394.
    OpenUrlPubMed
  26. 26.↵
    1. Giuliano AE,
    2. Ballman KV,
    3. McCall L,
    4. et al
    . 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;318:918–926.
    OpenUrlCrossRefPubMed
  27. 27.
    1. Bilimoria KY,
    2. Bentrem DJ,
    3. Hansen NM,
    4. et al
    . Comparison of sentinel lymph node biopsy alone and completion axillary lymph node dissection for node-positive breast cancer. J Clin Oncol. 2009;27:2946–2953.
    OpenUrlAbstract/FREE Full Text
  28. 28.↵
    1. Lyman GH,
    2. Giuliano AE,
    3. Somerfield MR,
    4. et al
    . American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer. J Clin Oncol. 2005;23:7703–7720.
    OpenUrlAbstract/FREE Full Text
  29. 29.↵
    1. Kuijs VJ,
    2. Moossdorff M,
    3. Schipper RJ,
    4. et al
    . The role of MRI in axillary lymph node imaging in breast cancer patients: a systematic review. Insights Imaging. 2015;6: 203–215.
    OpenUrl
  30. 30.↵
    1. Farrell TP,
    2. Adams NC,
    3. Stenson M,
    4. et al
    . The Z0011 trial: is this the end of axillary ultrasound in the pre-operative assessment of breast cancer patients? Eur Radiol. 2015;25:2682–2687.
    OpenUrl
  31. 31.↵
    1. Botsikas D,
    2. Kalovidouri A,
    3. Becker M,
    4. et al
    . Clinical utility of 18F-FDG-PET/MR for preoperative breast cancer staging. Eur Radiol. 2016;26:2297–2307.
    OpenUrl
  32. 32.↵
    1. Grueneisen J,
    2. Nagarajah J,
    3. Buchbender C,
    4. et al
    . Positron emission tomography/magnetic resonance imaging for local tumor staging in patients with primary breast cancer: a comparison with positron emission tomography/computed tomography and magnetic resonance imaging. Invest Radiol. 2015;50:505–513.
    OpenUrlCrossRefPubMed
  33. 33.↵
    1. van Nijnatten TJA,
    2. Goorts B,
    3. Voo S,
    4. et al
    . Added value of dedicated axillary hybrid 18F-FDG PET/MRI for improved axillary nodal staging in clinically node-positive breast cancer patients: a feasibility study. Eur J Nucl Med Mol Imaging. 2018;45:179–186.
    OpenUrl
  • Received for publication January 25, 2021.
  • Revision received March 19, 2021.
PreviousNext
Back to top

In this issue

Journal of Nuclear Medicine: 62 (12)
Journal of Nuclear Medicine
Vol. 62, Issue 12
December 1, 2021
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Complete Issue (PDF)
Print
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word on Journal of Nuclear Medicine.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Determining the Axillary Nodal Status with 4 Current Imaging Modalities, Including 18F-FDG PET/MRI, in Newly Diagnosed Breast Cancer: A Comparative Study Using Histopathology as the Reference Standard
(Your Name) has sent you a message from Journal of Nuclear Medicine
(Your Name) thought you would like to see the Journal of Nuclear Medicine web site.
Citation Tools
Determining the Axillary Nodal Status with 4 Current Imaging Modalities, Including 18F-FDG PET/MRI, in Newly Diagnosed Breast Cancer: A Comparative Study Using Histopathology as the Reference Standard
Janna Morawitz, Nils-Martin Bruckmann, Frederic Dietzel, Tim Ullrich, Ann-Kathrin Bittner, Oliver Hoffmann, Svjetlana Mohrmann, Lena Häberle, Marc Ingenwerth, Lale Umutlu, Wolfgang Peter Fendler, Tanja Fehm, Ken Herrmann, Gerald Antoch, Lino Morris Sawicki, Julian Kirchner
Journal of Nuclear Medicine Dec 2021, 62 (12) 1677-1683; DOI: 10.2967/jnumed.121.262009

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Determining the Axillary Nodal Status with 4 Current Imaging Modalities, Including 18F-FDG PET/MRI, in Newly Diagnosed Breast Cancer: A Comparative Study Using Histopathology as the Reference Standard
Janna Morawitz, Nils-Martin Bruckmann, Frederic Dietzel, Tim Ullrich, Ann-Kathrin Bittner, Oliver Hoffmann, Svjetlana Mohrmann, Lena Häberle, Marc Ingenwerth, Lale Umutlu, Wolfgang Peter Fendler, Tanja Fehm, Ken Herrmann, Gerald Antoch, Lino Morris Sawicki, Julian Kirchner
Journal of Nuclear Medicine Dec 2021, 62 (12) 1677-1683; DOI: 10.2967/jnumed.121.262009
Twitter logo Facebook logo LinkedIn logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One
Bookmark this article

Jump to section

  • Article
    • Visual Abstract
    • Abstract
    • MATERIALS AND METHODS
    • RESULTS
    • DISCUSSION
    • CONCLUSION
    • DISCLOSURE
    • Footnotes
    • REFERENCES
  • Figures & Data
  • Info & Metrics
  • PDF

Related Articles

  • This Month in JNM
  • PubMed
  • Google Scholar

Cited By...

  • Impact of 18F-FDG PET/MRI on Therapeutic Management of Women with Newly Diagnosed Breast Cancer: Results from a Prospective Double-Center Trial
  • Clinical Decision Support for Axillary Lymph Node Staging in Newly Diagnosed Breast Cancer Patients Based on 18F-FDG PET/MRI and Machine Learning
  • Virtual Biopsy: Just an AI Software or a Medical Procedure?
  • Google Scholar

More in this TOC Section

  • First-in-Human Study of 18F-Labeled PET Tracer for Glutamate AMPA Receptor [18F]K-40: A Derivative of [11C]K-2
  • Detection of HER2-Low Lesions Using HER2-Targeted PET Imaging in Patients with Metastatic Breast Cancer: A Paired HER2 PET and Tumor Biopsy Analysis
  • [11C]Carfentanil PET Whole-Body Imaging of μ-Opioid Receptors: A First in-Human Study
Show more Clinical Investigation

Similar Articles

Keywords

  • breast cancer
  • axillary lymph node metastasis
  • PET/MRI
  • oncologic imaging
SNMMI

© 2025 SNMMI

Powered by HighWire