Immunohistochemical analysis may not benefit negative sentinel nodes in breast cancer

Weaver DL. N Engl J Med. 2011;doi:10.1056/NEJMoa1008108.

Issue: February 25, 2011

Immunohistochemical analysis of initially negative sentinel nodes may not affect 5-year outcomes in patients with breast cancer, according to study results.

Researchers from several sites in the United States employed two screening strategies: sentinel lymph node biopsy plus axillary dissection or sentinel lymph node biopsy alone. Hematoxylin and eosin and immunohistochemical staining for cytokeratin were used at two widely spaced additional tissue levels. There were 3,887 patients in the final evaluation.

Occult metastases were found in 15.9% (95% CI, 14.7-17.1) of patients. Further analysis revealed that 11.1% of those metastases occurred in patients with isolated tumor-cell clusters, 4.4% occurred in patients with micrometastases and 0.4% occurred in patients with macrometastases.

Significant differences were observed between patients in whom occult metastases were detected compared with those in whom no occult metastases were detected regarding OS (P=.03), DFS (P=.02) and distant disease-free interval (P=.04), according to log-rank test results.

The corresponding adjusted HRs between the two groups were 1.40 (95% CI, 1.05-1.86) for death, 1.31 (95% CI, 1.07-1.60) for any outcome event and 1.30 (95% CI, 1.02-1.66) for distant disease.

Five-year Kaplan-Meier estimates in patients with detected metastases compared with patients without detectable metastases were 94.6% vs. 95.8% for OS, 86.4% vs. 89.2% for DFS and 89.7% vs. 92.5% for distant disease-free interval.

The researchers obtained paraffin-embedded tissue blocks of sentinel lymph nodes from patients with pathologically negative sentinel nodes. They then conducted central evaluation for occult metastases approximately 0.5 mm and 1 mm deeper in the block relative to the original surface.

The aim of the study protocol had a twofold purpose: to detect virtually all occult metastases larger than 1 mm in the greatest dimension and to randomly detect a proportion of occult metastases smaller than 1 mm that were present in the initially negative sentinel lymph node blocks, according to the results.

“Occult metastases were an independent prognostic variable in patients with sentinel nodes that were negative on initial examination; however, the magnitude of the difference in outcome at 5 years was small,” the researchers wrote. “These data do not indicate a clinical benefit of additional evaluation, including immunohistochemical analysis, of initially negative sentinel nodes in patients with breast cancer.”

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