Laying to rest sixty years of controversy in breast cancer treatment, researchers said there was minimal prognostic or survival rate value in analysing sentinel lymph node tissue for occult micrometastases, the tiny tumors sometimes found deep within tissue initially assessed as free of cancer.

You can read how the team, led by physician-researcher Dr Donald Weaver, from the University of Vermont (UVM) and Vermont Cancer Center in Burlington, Vermont, in the US, conducted the largest study ever undertaken in this area in a 19 January online first issue of the New England Journal of Medicine, NEJM.

The controversy over whether or not pathologists should do a deeper exam than the standard one of testing patients’ tissue samples started in the late 1940s when an influential breast cancer study publication reported that routine analysis of lymph nodes in breast cancer patients did not go far enough to find all the cancer that might be present.

Weaver, who is also professor of pathology at UVM, told the press that:

“The take-home message for women is that the micrometastases are so small, they have very little impact on outcome – only 1.2 percent at five years.”

“Pathologists shouldn’t continue to look for micrometastases when the initial evaluation is negative and oncologists shouldn’t treat patients any differently or change therapy exclusively based on micrometastases,” he urged.

He said the debate about whether breast cancer patients whose lymph nodes at first test negative for disease but who have occult metastases are at higher risk of recurrence, and thus should have more aggressive treatment, has been going on for years.

“It’s gratifying to finally have solid evidence that puts to rest the concern that micrometastasis substantially increases the risk of cancer recurrence or decreases overall survival in breast cancer patients whose sentinel nodes were initially negative for cancer,” he added.

Weaver and his team conducted a randomized cohort study as part of the National Surgical Adjuvant Breast and Bowel Project (NSABP) Trial B-32, a trial led by UVM’s Dr David Krag, and which recently reported findings in The Lancet Oncology.

In that report, Krag and colleagues said that doing a biopsy of the sentinel lymph node achieves the same cancer survival and recurrence control as the traditional surgical removal of the whole lymph node in patients whose initial sentinel lymph node biopsy result was negative for cancer.

In that broader trial, Krag and colleagues randomly assigned 5,611 patients with no clinical evidence of metastatic disease in the armpit (axillary) region to undergo either sentinel-lymph-node biopsy plus axillary dissection or just sentinel-lymph-node biopsy.

3,887 of those participants were enrolled in Weaver’s study, where the results showed that occult metastases were found in 15.9 per cent of patients whose initial sentinel node biopsy tested negative for cancer.

The results also showed that the overall 5-year survival rates among patients with detected and undetectable occult metastases were 94.6 and 95.8 per cent respectively, revealing a small difference of 1.2 per cent.

The researchers concluded that:

“These data do not indicate a clinical benefit of additional evaluation, including immunohistochemical analysis, of initially negative sentinel nodes in patients with breast cancer.”

For the study, the pathologists on the team evaluated all samples to find all metastases bigger than 2.0 mm by taking tissue slices of the sentinel lymph nodes every 2 mm, embedding them in blocks of paraffin wax, and then submitting them for analysis and detection.

All negative samples were then sent to UVM for further analysis where they sliced more finely, at 0.5 mm intervals.

“This evaluation protocol was designed to detect virtually all occult metastases larger than 1 mm and to randomly detect a proportion of occult metastases smaller than 1 mm that were present in the initially negative sentinel lymph node blocks,” wrote the authors.

Funds from the National Cancer Institute Department of Health and Human Services, PHS, and Vermont Cancer Center, helped pay for the study.

“Effect of Occult Metastases on Survival in Node-Negative Breast Cancer.”
Donald L. Weaver, Takamaru Ashikaga, David N. Krag, Joan M. Skelly, Stewart J. Anderson, Seth P. Harlow, Thomas B. Julian, Eleftherios P. Mamounas, and Norman Wolmark.
NEJM, published online 19 Jan 2011.
DOI:10.1056/NEJMoa1008108

Additional source: University of Vermont (press release, 19 Jan 2011).

Written by: Catharine Paddock, PhD