Last week the New England Journal of Medicine (NEJM) printed a major research article on lymph node dissection in breast cancer surgery. When I first saw the Times’ recent headline, I thought it would cover this paper: Effect of Occult Metastases on Survival in Node-Negative Breast Cancer.*
It turns out there were separate articles on axillary node dissection after sentinel node biopsy in breast cancer – one in JAMA and one in the NEJM – published a week apart. For some reason, the NEJM paper got little attention in the media.
In the work reported in the NEJM, investigators based at the Univ. of Vermont evaluated if the presence of occult metastases – cancer cells found upon further examination of dissected lymph node specimens after the sentinel nodes were deemed negative – affects survival in women with early-stage breast cancer. What they found was that yes, it does: there’s a small but significant reduction in overall survival and disease-free survival at 5 years in women who have “negative” sentinel nodes but turn out, upon more detailed path inspection, to have some malignant BC cells in the armpit.
Kinda scary for someone like me, who had a negative sentinel node. The Vermont investigators determined that 16% of us have occult mets. Of those, 11.1% would be isolated tumor-cell clusters (less than 0.2 millimeters in greatest dimension), 4.4% micrometastases (between 0.2 and 2 millimeters) and 0.4% macrometastases (larger than 2 millimeters), all as classified by the American Joint Committee on Cancer.
On the other hand, the results were generally favorable all-around:
“The 5-year Kaplan-Meier survival estimates for patients in whom occult metastases were detected were 94.6% for overall survival, 86.4% for disease-free survival, and 89.7% for distant-disease–free interval; the survival estimates for patients in whom occult metastases were not detected were 95.8%, 89.2%, and 92.5%, respectively.”
Some details on the well-done study I feel compelled to insert here, a vestige of my thrice-weekly-journal-clubs-in-academic-medicine days:
The Vermont study is strong from a statistical standpoint: The researchers examined stored pathology samples from 5611 women with operable, clinically node-negative BC who were already registered in a large multicenter clinical trial (NSABP B-32). The study participants were randomized to receive either sentinel node dissection or sentinel node dissection followed by full axillary lymph node dissection.
It was a prospective analysis, and the median time on study was just under 8 years. Of the 5611 women enrolled, 3887 (~70%) had negative sentinel nodes and sufficient pathology material available for evaluation. Oncologists treating the patients were “blinded” to the data regarding occult mets, so that they wouldn’t be influenced in their treatment decisions. Among the women with negative sentinel nodes, 1927 underwent sentinel node dissection followed by axillary node removal and 1960 got sentinel node dissection only (based on the earlier randomization).
One result not emphasized in the paper was that removing additional nodes, after the sentinel lymph node exam, didn’t affect the clinical outcome in women with or without occult mets. This finding ties in with this week’s JAMA report, covered separately.
It’s a long article, probably of more interest to pathologists and BC oncologists than to the average reader here. There’s a lot interesting detail, including subtle results of planned subgroup analyses, on the prognostic significance of different kinds (sizes) of occult mets.
I know from my experiences – mainly lately as a friend of people with BC who, in the past few years since sentinel node studies have become the norm – that these issues regarding the significance of occult mets bear on everyday decisions patients make together with their oncologists: how much chemo to take?; should I get radiation to the axilla if there’s a tiny cluster of cells found?; should we add Taxol to the regimen? etc.
These are very real, every-day questions in oncology, and the answers aren’t obvious. But I do think the carefully-established findings reported in this paper will shed light, in an incremental sort of way, on how to best treat BC in women who have negative sentinel nodes at surgery.