Review
Magnetic resonance for assessment of axillary lymph node status in early breast cancer: A systematic review and meta-analysis

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Abstract

Introduction

Current methods of identifying axillary node metastases in breast cancer patients are highly accurate, but are associated with several adverse events. This review evaluates the diagnostic accuracy of magnetic resonance imaging (MRI) techniques for identification of axillary metastases in early stage newly diagnosed breast cancer patients.

Methods

Comprehensive searches were conducted in April 2009. Study quality was assessed. Sensitivity and specificity were meta-analysed using a bivariate random effects approach, utilising pathological diagnosis via node biopsy as the comparative gold standard.

Results

Based on the highest sensitivity and specificity reported in each of the nine studies evaluating MRI (n = 307 patients), mean sensitivity was 90% (95% CI: 78–96%; range 65–100%) and mean specificity 90% (95% CI: 75–96%; range 54–100%). Across five studies evaluating ultrasmall super-paramagnetic iron oxide (USPIO)-enhanced MRI (n = 93), mean sensitivity was 98% (95% CI: 61–100%) and mean specificity 96% (95% CI: 72–100%). Across three studies of gadolinium-enhanced MRI (n = 187), mean sensitivity was 88% (95% CI: 78–94%) and mean specificity 73% (95% CI: 63–81%). In the single study of in-vivo proton MR spectroscopy (n = 27), sensitivity was 65% (95% CI: 38–86%) and specificity 100% (95% CI: 69–100%).

Conclusions

USPIO-enhanced MRI showed a trend towards higher sensitivity and specificity and may make a useful addition to the current diagnostic pathway. Additional larger studies with standardised methods and standardised criteria for classifying a node as positive are needed. Current estimates of sensitivity and specificity do not support replacement of SLNB with any current MRI technology in this patient group.

Introduction

Identification of axillary metastases in early stage newly diagnosed breast cancer is important for staging disease and planning treatment, but current techniques are associated with a number of adverse events. Approximately 40% of women who present with early stage breast cancer also have axillary metastases. The number of metastases present determines the stage of the disease, contributes to the overall prognosis and helps in the planning of adjuvant treatment. In the UK, women usually follow the diagnostic pathway described in the National Institute for Health and Clinical Excellence (NICE) guidelines1 (Figure 1). If women have a negative ultrasound or ultrasound-guided biopsy of the axilla, they proceed to sentinel lymph node biopsy. Sentinel lymph node biopsy (SLNB) is the excision of the first nodes to receive lymph from the breast (the sentinel nodes). Once removed, the lymph nodes are subject to histological analysis to determine the presence of metastases. If SLNB or the ultrasound-guided biopsy is positive, women proceed to axillary lymph node dissection (ALND), where all lymph nodes are removed to reduce the risk of uncontrolled axillary disease.

SLNB is a highly accurate method of identifying axillary metastases, and whilst it involves the removal of fewer lymph nodes than ALND, it is still associated with both short and long term adverse events. It is estimated that lymphoedema occurs in 21%2, 3, 4 of patients who undergo ALND and 7%5 of patients who undergo SLNB. Other adverse events include surgical complications such as risk of infection, seroma, insertion of surgical drains and sensitivity to the dyes used in SLNB. Non-invasive alternatives to these diagnostic tests could reduce the incidence of adverse events in women undergoing staging procedures. Any such technique would need to demonstrate acceptable sensitivity to avoid missing metastatic nodes and acceptable specificity to avoid false positive diagnoses, as well as acceptable levels of adverse events.

Magnetic resonance imaging (MRI) is a non-ionising, minimally-invasive in-vivo imaging technique. Unlike x-ray computerised tomography (CT), which uses the attenuation of ionising radiation as the basis of image contrast, standard MRI relies on the magnetic resonance characteristics of hydrogen nuclei (predominantly associated with water and fat) within the body. The technique utilises how these nuclei respond when placed in a magnetic field and are ‘excited’ by radio-waves during the application or switching of magnetic field gradients. The resultant signal is used to build up a set of images in 2 or 3 dimensions and, of particular importance, the contrast between different soft-tissues and pathologies can be highly informative, depending on many factors such as the hydrogen nuclei’s chemical environment. Of importance to axilla imaging, MRI can thus provide information about the size and morphology of lymph nodes. The administration of intravenous contrast media can give additional information. The presence of exogenous paramagnetic contrast media perturbs the magnetic field at localities where the media collects, which leads to alterations of local image contrast. This can increase lesion conspicuity (where the media collects) and provide additional information regarding the nature of pathological tissue based on the pattern of uptake. Such information can aid the judgement of whether a node is metastatic or not. As well as MRI of hydrogen nuclei attached to water and fat, the technique of proton MR spectroscopy (1H-MRS) can provide information regarding other molecules, the chemical status of which may be relevant to the presence of pathology. To consider MR imaging and spectroscopy as an alternative to SLNB, its sensitivity and specificity must be estimated. We have conducted a systematic review and meta-analysis to evaluate the diagnostic accuracy and adverse events associated with MRI for assessment of axillary metastases in early stage newly diagnosed breast cancer patients.

Section snippets

Search strategy

The systematic review followed the principles recommended in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)6, 7 statement. Eleven databases were searched in April 2009, namely MEDLINE, Medline in Process, EMBASE, CINAHL, Cochrane Database of Systematic Reviews, Cochrane CENTRAL Register of Controlled Trials, DARE, NHS EED, HTA database, Science Citation Index, and BIOSIS previews. The search strategy included terms for breast cancer, MRI imaging, the axilla or

Number and characteristics of included studies

Searches identified 658 unique titles for the broader review relating to imaging of the axilla. The full text of 138 titles were obtained and examined for inclusion in the broad review. Of these, nine titles16, 17, 18, 19, 20, 21, 22, 23, 24 representing nine studies met the inclusion criteria for this review, and were included. Three studies18, 21, 22 reported results for gadolinium-enhanced MRI, five16, 17, 19, 20, 23 for ultrasmall super-paramagnetic iron oxide (USPIO)-enhanced MRI and one24

Discussion

Overall pooled estimates of sensitivity and specificity for MRI were 90% and 90% respectively, with USPIO-enhanced MRI giving the highest overall diagnostic accuracy with sensitivity of 98% and specificity of 96%. Gadolinium-enhanced MRI gave sensitivity of 88% and specificity of 73% and MR spectroscopy gave a sensitivity of 65% and specificity of 100%. Confidence intervals were wide, and there was considerable variation in the criteria used to class a node as positive.

This study uses a

Conclusion

In summary, USPIO-enhanced MRI shows promising diagnostic accuracy for identifying axillary lymph node metastases in patients with early stage newly diagnosed breast cancer. Furthermore, MRI may make a useful addition to the current diagnostic pathway, by enabling more women to be correctly triaged for ALND, and avoid the need for two operations. However, there is a need for more and larger studies with standardised methods and standardised criteria for classifying a node as positive before any

Funding

This project was funded by the NIHR Health Technology Assessment Programme (project number 08/35/01) and will be published in full in the monograph series Health Technology Assessment. See the HTA programme website for further project information. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Department of Health.

Conflict of interest statement

The authors have no conflicts of interest.

References (27)

  • PRISMA statement website. www.prisma-statement.org....
  • K.L. Cooper et al.

    Positron emission tomography (PET) and magnetic resonance imaging (MRI) for the assessment of axillary lymph node metastases in breast cancer: systematic review and economic evaluation

    Health Technol Assess

    (2011)
  • TNM breast cancer staging

    (2009)
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