News in breast imaging: From elastography to molecular imaging
Presenting an overview of new imaging methods, radiologist Professor Ingrid Schreer (Mammazentrum Kiel), said the results of a multicentre prospective study on sonoelastography ‘…clearly show malignant lesions to have a significantly higher elasticity score than benign lesions. The best cut-off to differentiate benign from malignant lesions is a Uelo score of between three and four; one on the Uelo scale describes soft tissue and five stiff tissue. We arrived at a sensitivity of 96.9% and a specificity of 76.9%, which translates into diagnostic reliability of 82.9%.’
Shear wave technology builds on elastography with an added benefit: tissue stiffness can be evaluated not only qualitatively but also quantitatively. Currently, shear wave elastography is under study in 17 international centres. For BI-RADS 4 lesions the increased diagnostic specificity offered by shear wave is desirable, she pointed out.
Due to gamma camera advances, scintigraphy is experiencing a slight comeback in radiodiagnostics, although only reliable for detection of lesions larger than 11 mm. Specificity is about 60%.
High radiation exposure remains the major limitation of nuclear medical imaging. Positron emission tomography (PET) and single photon emission tomography (SPECT) visualise metabolic process in cells. Fusion imaging, a combination of PET and computed tomography (CT), further increases spatial resolution. However, Prof. Schreer pointed out that the spatial resolution offered by fusion imaging is still insufficient for primary tumour staging.
As a ‘by-product’ of tumour detection, visualisation of increased metabolic activity in cells also detects inflammatory processes. Currently, the visualisation of receptors on cells via molecular imaging technology is being explored. Using neo-angionesis non-invasively in screenings would be an interesting development, the professor noted.
Genetic profiling and proteases
Pathologist Professor Giuseppe Viale (European Institute of Oncology, Milan, Italy) spoke of the limitations and perspectives in genetic profiling and proteases. Although very optimistic about gene expression profiling, current molecular assays present some problems: These tools are prognostic, but not predictive – yet they are often handled as if the latter. Currently, two prospective clinical trials are testing the predictive value of molecular assays: MINDACT in Europe and TailoRx in the USA. Meanwhile, the list of the commercially available molecular assays grows. ‘I’m afraid there’s a certain pressure to use these assays in daily practice,’ he said. ‘First because we want to overcome the current uncertainties in the choice of therapy options; then because we like them – they’re sophisticated and fascinating -- and third, biotech companies are pushing hard to use these tests.’ As a take home message Prof. Viale reminded the audience that the identification of patient subgroups that could benefit from expression profiles still depends upon the accurate assessment of clinical-pathological and biological parameters. This assessment will reduce the level of uncertainty in the choice of the systemic treatment. Only then, the added benefit of expression profiles can eventually be ascertained.
Circulating tumour cells
Gynaecologist Professor Tanja Fehm (Women's Hospital at Tübingen University Hospital) explored the possible significance of circulating tumour cells (CTC) as a criterion in therapy selection. Since these cells’ survival time in the bloodstream is short, their presence indicates an active source such as metastases or relapse. ‘While the prognostic significance of CTC in adjuvant therapy is not clearly proven yet, current studies show promising results,’ Prof. Fehm pointed out. Patients who test positive on CTCs show a markedly increased relapse rate. However, this result cannot be replicated after chemotherapy. In therapy monitoring CTCs might act as an indicator for secondary adjuvancy and thus help to optimise adjuvant therapy strategies.
‘When metastases are present,’ she continued, ‘CTCs are already being used as prognostic markers. After the first chemotherapy cycle CTCs already show whether the body responds positively to the therapy. ‘We might want to explore whether CTCs can, if necessary, be used after a month to indicate whether a change of therapy is advisable rather than waiting for three therapy cycles to be completed and then use imaging for therapy monitoring purposes,’ he suggested, adding that, in therapy monitoring, CTC might fill a gap in real-time biopsy since the phenotype of the CTCs corresponds to the phenotype of the metastases. This means that the CTCs can be characterised in a blood sample and thus give an indication of the phenotype of the metastasis. Comprehensive clinical studies are still required on this issue.
In his closing presentation, Surgeon Dr Peter Schmid (Charing Cross Hospital and Hammersmith Hospital, Imperial College London, UK) introduced epigenetics. Epigenetic factors are changes ‘imposed’ on the DNA sequence that controls gene expression; they are the switches that turn genes on and off. One of the most important epigenetic regulation mechanism is DNA methylation, which marks active and inactive DNA areas. Epigenetics, and above all methylation, are clinically significant because they deactivate tumour- suppressant genes. Thus Methylation can be used to influence the sensitivity of therapies. Epigenetic profiles undergo dynamic processes that can be recognised after only a few weeks, or even days. Moreover, epigenetic markers might have prognostic or predictive relevance. However, this has not yet been sufficiently validated. Dr Schmid expects epigenetic profiles of plasma DNA to become particularly important. ‘Further research is required to determine the place of epigenetics next to molecular pathology and gene expression profiling,’ he concluded.