For the past century or longer the conventional view has been that wide and careful removal of solid tumors was required for cure. In breast cancer this view was challenged by the series of trials led by the NSABP showing that the modified radical mastectomy was no worse than breast-conserving surgery. Clearly, some microscopic metastatic disease was left behind after both surgical procedures, but increasingly effective systemic adjuvant therapies were able to eradicate or control at least some of this, and, in any case, the extent of local surgery did not change this burden.
Said more plainly, the chances for a long life without distant recurrence were not different with more versus less radical surgery.
If the extent of breast surgery itself is not critical to the cure of breast cancer it is appropriate to ask about the functional role of axillary dissection. This local therapy causes some of the more troubling long-term consequences of breast cancer including decreased range of motion in the shoulder, increased risk of infection, risk of lymphedema, and pain.
In this context, the results of the ACOSOG Z0011 study in the February 16th issue of the Journal of the American Medical Association (Giuliano et al: http://jama.ama-assn.org/content/305/6/569.full) are provocative and important. Patients with small (but typical) breast cancers, mostly hormone receptor positive, were treated with limited excision (and planned radiation therapy) and subjected to sentinel node biopsy. If they were found to have one or two nodes with involvement using conventional testing, they were randomized to no further axillary surgery or to axillary dissection.
The possible omission of a full axillary dissection following the discovery of positive sentinel nodes was bold and considered radical—if not harmful—by some potential investigators, limiting potential participation. Indeed, the study was not completed in terms of planned accrual, but the results in the nearly 900 patients randomized are none-the-less compelling, because if anything they run somewhat counter to expectations.
Furthermore, given what has been seen thus far it is highly unlikely that completion of the trial would meaningfully change the results.
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About a quarter of patients who went on to complete axillary dissection had positive nodes. This suggests that about a quarter of the patients who did NOT have dissection harbored positive nodes. Despite this increased tumor burden in the axilla, there were very few axillary recurrences in either randomized arm and no difference in the small number of local and regional recurrences.
Similarly there were no discernable differences in disease-free or overall survival. In this context it is important to acknowledge the recent report by Weaver et al of the NSABP B-32 study (NEJM 2011; 364:412-421). Here, small numbers of presumably malignant cells in the sentinel node were poor prognostic features. The critical issue, however, is whether their removal actually changes their impact—Z-0011 suggests not.
For medical oncologists, these results suggest that for patients with good-prognosis tumors treated with modern adjuvant therapy and radiation, it is not necessary to remove small numbers of involved axillary nodes to obtain an excellent outcome.
Critical Concept: Difference Between Prognosis & Prediction
Whether this holds up over the longest term remains to be seen, but in the meantime this highlights a critical concept: The difference between prognosis and prediction. Putting aside the quality of local control, for most of our careers medical oncologists have used poor prognosis, as indicated by involved nodes, to select patients for more “aggressive” (read as chemotherapy) adjuvant treatment. In a sense we were assuming an even effect of chemotherapy such that with higher risk the benefits would outweigh its risks.
However, we don't do that with trastuzumab or hormone therapy. Instead, for these targeted therapies we look for biological predictors of response (HER2, ER) and plan treatment accordingly and, to a degree, independently of risk (prognosis).
With the development of genomic and other predictors of chemotherapy sensitivity we may be liberated from reliance on node status as a surrogate for chemotherapy benefit. If so, then medical oncologists might be able to make systemic treatment decisions based on biology rather than anatomy.
If our surgical colleagues can demonstrate, as suggested by Z-0011, that local control is unaffected by the extent of local therapy (at least in a subset of low-risk patients), then we can offer as, or more, effective therapy at lesser total toxicity cost. This is a move in the right direction.
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© 2011 Lippincott Williams & Wilkins, Inc.