The Evolving Role of Radiofrequency Ablation Therapy of Breast Lesions

Ultrasound-guided Radiofrequency Ablation

It is well established that ultrasound us is a key imaging modality in the detection and monitoring of breast disease, both malignant and benign in nature. Furthermore, us-guided techniques, including percutaneous needle biopsy, have proven to be an indispensable tool for the diagnosis of breast cancer. In recent years, us has been employed as part of a new therapeutic intervention, RFA. Although this procedure was initially used for the treatment of metastatic liver disease (5), it was not long before its potential to treat other tumours types including breast cancer was identified.

The first feasibility study for breast RFA was conducted by Jeffrey et al. in1999 (6). They trialled its use in five women with localised (stage III) breast carcinoma. A technique was proposed whereby a multi-pronged electrode was placed into the centre of the lesion. In this initial study, a mean power of 36 W was supplied for 30 minutes. The progress of tissue ablation was tracked via US, where an expanding area of hyperechoicity represents the ablation zone. Immediately after RFA, the tumours were excised by mastectomy. Tissue staining of the tumours with nicotinamide adenine dinucleotide–diaphorase (NADH–diaphorase) revealed the presence of viable tumour cells in one patient, thus giving a success rate of 80%. This study highlighted one of the principal concerns with RFA i.e. the uncertainty of complete ablation. Unfortunately this problem has not been resolved, although some groups have reported 100% success rates (7-9). The problem is inherent to the technique. It is difficult to accurately determine the three-dimensional proportions of the tumour with US; additionally, matching of the RFA zone to the tumour shape is difficult due to the inability to accurately visualise the zone of ablation. Several solutions to this problem have been proposed.

Electrode design is central in effectively directing the current to all parts of the tumour. It has long been established that a tissue temperature of around 45°C is required before necrotic cell death occurs (10). The ideal electrode would supply uniform heating to all areas of the tumour. Currently there are two princial designs, the multi array as used by Jeffrey et al. or the single needle with an infusion of cold saline (6). The aim of the single needle set-up is to avoid charring and thus prevent a rise in tissue impedance, allowing greater heat dispersion. The multi-array system is designed to place electrodes evenly throughout the tumour. However, this requires more force and can be technically challenging, resulting in poor electrode distribution (11, 12). An ex vivo model suggested that the single cooled needle system is more efficacious in tumour ablation (13). However, a recent comparative review of ablation techniques found no significant difference in the two designs (14).

To date, a number of RFA studies have suggested that post-ablative core biopsy, US and magnetic resonance imaging might be sufficient for patient follow up (15-17). All three studies demonstrated impressive results, with none of the tumours showing recurrence at between 3-18 months follow-up. A series of studies with a variable delay in tumour resection after RFA, show an increase in the percentage of tumours which showed no residual cancer cells on NADH–diaphorase staining (see Table I). One explanation for these impressive results suggests that tissue thrombosis and hence tissue necrosis and immunological response increase with time.

Results from several studies have suggested that complete tumour ablation may be dependent on tumour size. An RFA study using the single cooled needle method, evaluated ablation efficacy in 20 patients with tumours >2 cm and 29 patients with tumours ≤2 cm (20). They found complete tumour ablation rates of 30% and 86% respectively. Similar results were seen in a second study of 14 patients with tumours ≤2 cm and 11 patients with tumours >2 cm with ablation rates of 93% and 55% (21). These findings agree with numerous other studies where tumour sizes of <2cm showed ablation rates of between 90-100% (7, 8, 18-19). The strong concordance between the good success rates in the <2 cm groups suggests that RFA may be more appropriate for smaller tumours.

Two studies have demonstrated particularly good results when RFA is used in elderly patients (mean ages 80.5 and 81 years) (15, 16). These studies both reported no viable malignant tissue at 3 and 18 months respectively. However, neither of the studies performed consequent surgical excision of the tumours therefore it is difficult to objectively assess tumour ablation. Since RFA is performed under local anaesthesia, it has the potential to be the therapeutic intervention of choice in frail elderly patients unfit for general anaesthesia and open surgery.

Across multiple studies, increased tumour impedance has been shown to reduce the effectiveness of RFA. High impedance is associated with an increased fat content of tumours due to the high electrical resistance of fat. Within the elderly population, age-related breast atrophy results in a lower tumour fat content compared to younger groups. Thus, RFA may be more successful amongst this group as a direct result of reduced resistance to thermal energy.

MRI-Guided Radio frequency Ablation

The use of MRI for screening, diagnosis and management of breast cancer is gaining popularity. It has long been established that MRI is highly sensitive for the detection of benign and malignant abnormalities that are often concealed on other imaging modalities such as mammography and US (22). Furthermore, due to the sensitivity of MRI to temperature changes, it is exceptionally suited to guide RFA. MRI can potentially allow monitoring of the ablation process in real time. This has the benefit of the continuous intraprocedural assessment of the completeness of ablation (22). The majority of RFA studies to date have used real time US to monitor the ablation process. However, many authors question the true accuracy of US for this procedure (24). Specifically, the combination of the hyperechogenicity of heated breast tissue and US shadowing can make it difficult to differentiate between residual breast tumour and the ablated tissue (22). Therefore, malignancy may be left behind unknowingly in these patients.

To date, only two main studies have evaluated MRI-guided RFA in humans (Table II). Van der Bosch et al. (24) treated three female breast cancer patients with MRI-guided RFA. In this study, the MRI guided technique allowed four areas to be closely monitored throughout the procedure: i) the breast tumour undergoing ablation; ii) normal breast parenchyma away from the region to be ablated; iii) retromammary fascia at the breast/chest wall border; iv) subcutaneous tissue along the probe tract (24). The initial results from this preliminary study were promising. All three patients tolerated the procedure well, with no complications or burning reported post procedure. Within a week following RFA, two patients had a lumpectomy and one patient had a mastectomy. The ablated and surrounding tissue underwent histopathological analysis to determine the success of ablation in each case. In the first patient, pathological analysis illustrated necrotic ablated tissue and no viable tumour cells. However, in the second patient, analysis of the lumpectomy specimen revealed residual invasive ductal carcinoma and in this case only 50% of the tumour had been successfully ablated with RFA. In the final patient, only 33% of the tumour had been ablated; post mastectomy specimen analysis also revealed residual infiltrating ductal carcinoma and an insitu ductal carcinoma in this patient. While the authors clearly demonstrated the accuracy of MRI in identifying breast cancer and the ability to monitor various regions during the procedure itself; successful ablation was only achieved in one patient.

More recently, Yamamoto et al. conducted a pilot study on 26 patients using MRI guided breast RFA (25). The ablated tumours were histologically evaluated using hematoxylineosin (H&E) and nicotinamide adensine dinucleotide (NADH) diaphorase staining. The results illustrated that 92% of the patients (24 out of 26) had complete ablation of the tumour, since no viable tumour cells were found on histological analysis (25). The authors report complications in four patients: three patients suffered small diameter grade three burns to the skin (two to the outside of the thigh from grounding pad and one to the breast skin itself). In addition, one patient was noted as having a significant adverse breast lesion similar to chronic granulomatous mastitis as a result of overreaction of the ablated zone. This larger study compared to that conducted by Van der Bosch et al. suggests that MRI-guided RFA could potentially be an accurate and safe application for patients with small breast tumours. These encouraging results could be attributed to the larger cohort of patients recruited in this study. In addition, Yamamoto et al. adopted a shorter ablation time but with a higher temperature (25). However, in order to establish whether this technical difference is significant in terms of ablation success, further studies would need to be carried out.

RFA of Benign Breast Tumours

The management of benign breast tumours encountered on percutaneous biopsy has also been at the centre of recent debates i.e. surgical excision versus follow up. Furthermore, strong data to aid the decision are lacking within this particular field (26). The development and introduction of breast conserving treatments including RFA, offers a potentially different route from the conventional surgical excision of benign lesions. In addition, due to the benign nature of these tumours, the issues surrounding RFA for small breast tumours i.e. the concern of incomplete ablation is not a primary concern in benign breast disease. It is clear that further research is required in this particular field, since, to date, no studies have been carried out to evaluate the potential role of RFA in benign breast disease.