The state of sentinel lymph node biopsy

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Axillary node status is important to accurately stage breast cancer. With earlier detection, only about 30% of all symptomatic breast cancers are node positive. There are no reliable clinical or imaging studies that accurately stage the axilla. Conventionally, axillary dissection to remove most or all the lymph nodes that drain the breast is recommended to stage and treat the axilla. However, this procedure is therapeutic only in those found to be node positive. Axillary sampling of four nodes in the low axilla was used as an alternative, observing the axilla in those found to be node negative. Those who were node positive on sampling had the choice of completion axillary dissection or radiotherapy. Sentinel lymph node biopsy (SLNB) aims to reduce the morbidity from formal axillary surgery in patients who are clinically lymph node negative. There is no doubt from the proliferation of literature on this subject in the medical journals over the last four years that the technique is reliable. Most studies thus far have looked at the efficacy of SLNB in patients who subsequently had completion axillary dissection, comparing SLNB and conventional surgery in the same individual. Localisation of the sentinel lymph node by radio-isotope or blue dye, or both in combination, appear effective and each have their enthusiasts. True positive and true negative sentinel nodes compared to axillary node status determined by conventional surgery are accurate using these techniques. Difficulties arise when sentinel nodes are falsely negative, that is when the SLNB is negative but a positive lymph node is found elsewhere in the axilla at conventional surgery. If SLNB is used as the sole staging method in such women, understaging of the axilla may lead to overestimation of prognosis and possible undertreatment of the breast cancer.

There is still no reliable and efficient intraoperative method of knowing if the SLNB contains tumour, thus allowing completion axillary dissection at the same operation in patients who are SLNB positive. Frozen section (immediate assessment using a special histological technique that takes about 30 minutes) has a variable efficacy. Touch preparation, where the sentinel node imprint is left on a glass slide and stained for cytology analysis is beginning to show more promise. Special stains using antibody techniques for breast cancer cells within the lymph node take time and result in unnecessarily long general anesthetics for many women. If the final diagnosis of SLNB is made after conventional histology, the results are only available several days after the operation, and if positive, will require further surgery to complete the axillary dissection. Although it is possible to treat the SLNB positive axilla with radiotherapy in the absence of palpable involved lymph nodes, the nodal burden (number of positive nodes to total retrieved) is an important prognostic factor. The safety of merely observing the axilla on the basis of a negative SLNB is not clearly established. In principle, the concept does appear sound, but has not been proven in clinical trials (the gold standard by which new treatments are accepted in medicine).

There is a further outstanding issue. Knowledge on node status has always been on histologically obvious tumour invasion of the lymph nodes (on microscopy) in an axillary dissection, that typically contains 10-20 nodes. With sentinel lymph node biopsy, only 1-3 lymph nodes are submitted and these are subject to rigorous histological analysis, usually by examining multiple tissue sections, in excess of that used in conventional histology. In addition, many centres also subject the sentinel lymph node(s) retrieved to sophisticated special staining techniques (immunochemistry) that can pick up isolated breast cancer cells within the lymph nodes that are invisible to conventional histopathological methods. Some centres also use very sensitive scientific methods that detect cells at the DNA level (polymerase chain reaction), which identify tumour cells that would never have been detectable by microscopic examination. The implication of this (termed microinvasion) on prognosis and outcome after breast cancer treatment is unknown.

The implication of treating women on the basis of SLNB is being addressed in the ALMANAC study in the United Kingdom. Women who are SLNB negative have their axillae observed while those who are SLNB positive either have a completion axillary dissection at a second operation, or have axillary radiotherapy.

With current understanding of breast cancer, decisions on adjuvant chemotherapy are based upon pathological variables of the primary cancer as well as axillary node status. The relative indications for chemotherapy in addition to node positivity include any grade III cancer, tumours greater than 15-20mm, the presence of vascular invasion, young age and hormone insensitivity. SLNB may be a useful means of obtaining node status for this purpose in the future. A similar case can be made for SLNB prior to starting primary chemotherapy for tumours greater than 3cm and less than 5cm that are clinically node negative. Until we know more about SLNB, this technique should be considered as research and women who are interested should be offered entry into clinical trials. Women who request SLNB off study should be adequately counselled of the uncertainties.

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