by ecancer reporter Clare Sansom
 

When breast cancer is diagnosed, it is important to determine whether cancer cells are present in the lymph nodes (i.e. if the cancer is node positive) and to identify and remove all lymph nodes containing these cells.

Lymph nodes may be removed as a precautionary measure in patients diagnosed with node negative cancer, but this procedure is quite invasive.

The standard procedure for node removal, which is used particularly for patients with node positive disease, is axillary lymph node dissection (ALND) in which the armpit, or axilla, is incised in order to identify and remove affected nodes.

This procedure offers excellent cancer control to patients with both node positive and node negative disease but at the cost of some morbidity.

Sentinel node biopsy (SLN) is an alternative procedure in which a dye or tracer substance is injected into the breast to identify the sentinel nodes: these are the most likely to be affected.

Clinical trial results of SLN biopsy following systemic therapy in patients with limited lymph node involvement have shown that this therapy controls cancer as well as the more invasive ALND procedure.

However, prospective studies have typically found false negative rates of 7% to 10% for this procedure and ALND is still considered the standard option for patients diagnosed with node positive disease.

Further clinical trials have been set up to determine the circumstances in which SLN biopsy is as effective as ALND and therefore in which the less invasive treatment can be recommended.

Results from the ACOSOG Z1071 (Alliance) Phase II trial of SLN surgery after neo-adjuvant chemotherapy by Judy Boughey and her colleagues on behalf of the Alliance for Clinical Trials in Oncology were recently published in the Journal of the American Medical Association [1] and discussed by Monica Morrow and Chau T. Dang, in an accompanying editorial [2].

This trial was designed to determine the false negative rate of this intervention in women diagnosed with breast cancer graded N1 (that is, with regional lymph node involvement only) and no other metastases.

A total of 756 women were enrolled in the trial, and 649 of these underwent both ALND and SLN in accordance with the trial protocol.

No sentinel nodes were detected in 46 of these patients, one in 78 and two or more in the remaining 525 (81%).

All sentinel nodes detected were removed and tested for cancer, as were all other nodes detected through ALND.

In 215 of the 525 patients with two or more sentinel nodes identified, no cancer was found in these nodes.

Cancer was detected in nodes identified only through ALND in 39 of these 215 patients.

This represents a false negative rate of 12.6% (90% CI 9.85%-16.05%), which is higher than the 10% quoted for SLN in patients with node negative cancer undergoing this procedure alone.

Boughey and her co-workers concluded that this false negative rate was not low enough to justify the standard use of this treatment in patients diagnosed with N1 breast cancer without changes to the criteria for patient selection.

In discussing this study, Morrow and Dang suggest that despite its inherent interest, the setting chosen was perhaps not the most appropriate.

In particular, they note a relationship between the number of sentinel nodes identified in the biopsy and the false negative rate: the fewer sentinel nodes were identified, the more likely that patient was to have cancer detected in other nodes (i.e. to be classed as false negative).

A similar relationship has been observed in the SENTINA trial, which only considered patients who were re-classified as node negative following chemotherapy.

Both these trials have shown that it is only when SLN detects at least three sentinel nodes that the false negative rate is reduced to the 10% or less that would be required for the treatment to be adopted as standard.

Furthermore, other trials have indicated that patients with small amounts of cancer remaining in their axillary nodes after treatment do not develop metastatic cancer at a higher rate than those who do not, that is, that false negative results from SLN are unlikely to be clinically important.

Accurate detection of residual lymph node cancer is, however, likely to be important in identifying the most appropriate patients for trials of novel drugs for post-neoadjuvant therapy.

Morrow and Dang conclude their editorial by agreeing that SLN should not be considered as standard treatment for node positive breast cancer, and suggest that further research is required to identify its most appropriate place in the expanding menu of personalised treatments for this disparate disease. 

References

[1]: Boughey, J.C., Suman, V.J., Mittendorf, E.A. and 18 others (2013). Sentinel Lymph Node Surgery After Neoadjuvant Chemotherapy in Patients With Node-Positive Breast Cancer: The ACOSOG Z1071 (Alliance) Clinical Trial. JAMA 310(14), 1455-1461. doi:10.1001/jama.2013.278932

[2]: Morrow, M. and Dang, C.T. (2013). Sentinel Node Biopsy After Neoadjuvant Chemotherapy: A New Standard for Patients With Axillary Metastases? JAMA 310(14), 1449-50. doi:10.1001/jama.2013.7844