Significance of axillary lymph node extranodal soft tissue extension and indications for postmastectomy irradiation

Mignano et al. report on the important entity of extranodal extension in Axillary Lymph node (ALN) positive breast carcinoma.1 This entity, as the authors indicate, has been reported in the literature, with the majority of studies reporting a higher rate of locoregional and systemic recurrences, compared with cases without extranodal extension. The authors report on 43 cases with extranodal extension from 487 clinical T1-T3, pN1 breast carcinoma cases diagnosed between 1974–1994 at their single institution. All patients underwent a modified radical mastectomy and 58% received systemic adjuvant treatment but no patient received adjuvant locoregional radiation. Their results showed that the extranodal positive subsets had significantly lower disease free and overall survival rates and a significantly higher proportion of patients had greater than four positive ALNs. Authors observed that despite high overall recurrence rates in patients with extranodal extension, the risk of axillary recurrence, either as an isolated event or as a part of simultaneous failure, was extremely low. Therefore, the authors concluded that although these patients with extranodal extension may be considered for radiation treatment on the basis of having a high number of positive lymph nodes, the presence of extranodal extension alone is not an indication for routine axillary radiation. We agree with the authors that extranodal extension does have a higher association with recurrence and breast carcinoma mortality, and a significant association with a higher rate of positive lymph nodes. Similar findings were found in the analysis of the British Columbia randomized trial.2 However, we disagree with the conclusion that because of a low rate of axillary recurrences, axillary radiotherapy is not required in these patients. Axillary recurrences are infrequent in ALN positive patients and do not adequately reflect the potential for systemic dissemination. Although the British Columbia trial reported 61% systemic recurrence rate in the chemotherapy-alone arm, the rate of locoregional recurrence was only 23%,3 and that of isolated axillary recurrence was only 6%.4 Therefore, the majority of systemic recurrences (> 70%) took place in the absence of locoregional failures, and > 90% of all systemic recurrences were noted without axillary failure. Recent large, prospectively randomized trials have shown that locoregional radiotherapy will reduce systemic recurrences and thus decrease breast mortality significantly in ALN positive breast carcinoma cases.3, 5, 6 In all trials, locoregional radiation therapy was used uniformly, and hence the omission of axillary or other radiotherapy fields, in any subset, may depreciate the significant survival gains documented. The update of British Columbia trial also showed that patients with N1-3 lymph nodes had a substantial radiation therapy survival benefit (relative risk [RR] = 0.65), with more significance in a subset of patients with extensive lymph node/extracapsular spread (EESN, RR = 0.47; P = 0.035). However, the importance of EESN was not established when locoregional recurrences alone were analyzed. EESN is a broader category of risk than extranodal extension alone because it includes extensive lymph node replacement as well as extracapsular spread. Yet both have one basic commonality: they both express extensive lymph node involvement/replacement and select for biologically more aggressive disease. Our data show, in a randomized trial, that radiation therapy will confer in those subsets a substantial survival benefit. Thus, the extranodal extension may be of particular signifigance in patients with N1–3 disease who presently are not considered for routine radiation therapy. This considerable benefit of radiation on breast cancer mortality in EESN positive cases would be entirely missed if only axillary recurrences were analyzed and considered as an indication for radiation therapy. Joseph Ragaz M.D.*, Stewart M. Jackson M.D. , * Department of Medical Oncology, Department of Radiation Oncology, British Columbia Cancer Agency, Vancouver, British Columbia, Canada

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