The absolute number of positive lymph nodes dissected from the axilla is currently recognized as the most significant predictor of survival in breast cancer [5
]. It is intuitive that the fewer the number of lymph nodes removed in dissection of the axilla, the less reliable this predictor will be, with significant potential for understaging and under treating. Exactly what constitutes an “adequate” axillary dissection, however, in terms of providing sufficient prognostic and therapeutic benefits, remains a topic of considerable debate. In contemporary series of patients with early breast cancer, when 7–10 lymph nodes are identified in the axillary specimen, fewer than 3% of patients will experience axillary failure [3
]. Most studies assessing the extent of dissection required to accurately assess nodal status suggest that >
10 nodes should be examined [11
]. To a certain extent, the variation in the total numbers of “axillary nodes removed” between series of patients reflects not only differences in surgical technique, but also in the pathologists' examination of the specimens.
The concept of the nodal ratio was developed in order to reduce the confounding of the number of involved lymph nodes by the extent of surgical clearance and thoroughness of pathologic examination. By combining the “involved” and “examined” nodes into a single value, the prognostic implications of axillary dissection may be more reliable and may potentially lead to better selection of patients requiring adjuvant regional nodal therapy. In addition, for comparison of different series of patients, the nodal ratio can serve as a uniform standard value. Nodal ratio has been particularly useful when looking at patients with 1–3 positive nodes and/or inadequate dissections, as these have historically been groups for whom the decision to use adjuvant radiation therapy is considered controversial.
Outcomes are worse with higher numbers of positive nodes and with higher nodal ratios, with a number of studies suggesting that the latter is the stronger of the two prognostic factors. The nodal ratio has been shown to be predictive for breast cancer outcomes in a variety of clinical scenarios (e.g., early-stage and locally advanced, mastectomy and BCT, ± chemotherapy, and/or radiation) [8
]. These studies have found nodal ratios to be predictive of a variety of outcome parameters including locoregional relapse, disease-free survival (DFS), progression-free survival (PFS), cause-specific survival (CSS), overall survival (OS), and metastasis-free survival. Furthermore, nodal ratios have also been used to rectify interinstitutional differences in outcomes that exist due to variations in axillary dissection practice [18
]. These findings are reviewed in a recent comprehensive publication of the prognostic value of nodal ratios [2
Among the studies that have used nodal ratio as a prognostic indicator, various thresholds have been used for definition of a “high” ratio. Our definition of high nodal ratio was similar to the publications by Tai et al., the International Nodal Ratios Working Group, and others, that used ratios of >50%–75% for their high nodal ratio group [2
]. In the above-mentioned review of nodal ratios that included >20 clinical studies, the percentage cutoffs for nodal ratios varied depending upon the outcomes being investigated and the level of statistical significance being sought [2
]. Hence, there has yet to be established a clear benefit to the use of any one method of grouping patients by nodal ratio over any other.
Our study suggests that high nodal ratios of >70% are predictive of supraclavicular relapse in women with early-stage breast cancer who have had at least 8 nodes excised on ALND. It is important to note that while the vast majority of these patients received supraclavicular radiation, the fields were determined clinically in the era in which these patients were treated, with the dose prescribed routinely at a depth of 3
cm, without CT guidance, as was the convention at our institution. More recent investigations in the CT treatment planning era suggest that the depth of the supraclavicular nodes varies significantly, ranging from 2.4–9.5
cm (median = 4.3
]. Given this variability in depth and the substantial risk of supraclavicular recurrence in the high nodal ratios risk group, meticulous attention should be paid by the treating radiation oncologist to contouring the location of the supraclavicular lymph nodes with careful selection of the radiation beam energy, with consideration given to a supraclavicular boost in high-risk patients to ensure optimal delivery of dose to these lymph nodes at potential risk for recurrence.