Sentinel node biopsy in breast cancer

The status of the axillary lymph nodes in a woman with breast cancer is the single most important prognostic factor, and important clinical decisions are based on it. In the absence of non-invasive methods, it has become routine either to perform a partial axillary dissection to stage the axilla or to remove completely all axillary lymph nodes to both stage and treat the axilla. With the development of screening, increasing numbers of women are seen who are node negative. In these patients extensive axillary surgery is difficult to justify because most women gain no significant benefit and suffer considerable morbidity from the axillary surgery. Research has focused on developing procedures that assess axillary lymph node status while minimising morbidity.

Twenty years ago Cabanas showed the existence of a specific draining lymph node, the so called “sentinel” lymph node, which could be identified after lymphangiography through the dorsal lymphatics of the penis.¹ He confirmed that the first node visualised, the sentinel node, was the first site of metastases and reported that it was often the only affected lymph node. Unaware of this report, in 1992 Morton and colleagues developed cutaneous lymphoscintigraphy as a method of identifying nodal areas at risk of metastases in patients with malignant melanoma.² They showed preferential drainage to one or two nodes in a particular lymph node group. Applying this concept to breast cancer, we would expect that if malignant cells spread to a regional lymph node then they should follow the same route as lymph draining from the primary carcinoma. If the draining or sentinel node from a breast cancer can be identified and is free of metastasis then theoretically the other axillary nodes should also be free of disease.

Early studies of sentinel nodes in breast cancer used a vital blue dye. The initial rate of sentinel node identification with this technique was 66%, although success has improved with experience.³,⁴ No sentinel nodes outside the axilla were identified with this technique. The blue colour appears in the axillary lymphatics and nodes within a few minutes of injection and can be visualised, but before surgery it is not possible to ascertain where in the axilla the sentinel node lies. Injecting a gamma emitting radiopharmaceutical around the primary tumour permits preoperative visualisation of the draining node using a gammacamera and has shown that the sentinel node is in the internal mammary chain in up to 6% of patients.⁵ Using a hand held gamma probe, the surgeon can locate the node with the highest uptake and make an exact skin incision directly over it, which limits the dissection and associated morbidity of the axillary staging procedure. By using different pharmaceutical agents radioactivity can be identified in sentinel nodes 1-16 hours after injection. With technetium labelled albumin sentinel nodes were identified in all but three of 241 patients in one study, with an overall accuracy compared with a full axillary clearance of 97.5%, a false negative rate of 4.6%, and a sensitivity of 94.7%.⁶

There would be an obvious advantage if the sentinel node or nodes could be assessed intraoperatively, so that a patient with affected nodes could have the option of proceeding immediately to a full axillary dissection. Routine frozen section examination appears to miss up to 30% of metastases in sentinel nodes.⁶ A newer, more accurate technique using multiple sections and an immunohistochemical technique to reveal epithelial cells has been described but takes up to 40 minutes to perform.⁷ Until this technique has been refined and its accuracy confirmed in other centres, intraoperative assessment of sentinel nodes cannot be recommended.

Sentinel node biopsy is a promising technique, but before it can be introduced into routine practice the technique of node identification needs to be optimised and it needs to be compared with other surgical options for axillary node staging.⁸ The available data suggest that both a radioactive tracer and supravital dye are needed to provide a satisfactory rate of sentinel lymph node identification.⁹ The best carrier agent for radioactivity, site, volume of injection, and interval between injection and surgery remain to be defined.⁵,⁷ Thereafter it will be necessary to show that different surgeons with a range of skill in axillary surgery can produce a satisfactory rate of sentinel node identification. Then and only then should multicentre randomised trials comparing sentinel node biopsy with standard techniques of assessing axillary lymph node disease be performed. Introduction of this technique into clinical practice before results from these randomised trials are available cannot be supported.