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Patients with breast cancer with distant lymph node metastases (DLNM) had similar survival to that of patients with regional node involvement and significantly better survival than those with non-DLNM distant spread, an analysis of 2,000 cases showed.

Women with DLNM at diagnosis had a 3-year breast cancer-specific survival (BCSS) rate of 64.54% versus 63.24% for patients with ipsilateral supraclavicular lymph node metastases (ISLM) and 41.20% for those with distant metastases. Overall survival (OS) at 3 years was also similar between ISLM and DLNM, but significantly worse for patients with non-DLNM distant metastases.

The results, derived from (SEER) registry data, suggest that DLNM should be considered regional disease warranting aggressive treatment, reported Wenbin Zhou, MD, PhD, of Nanjing Medical University in China, and co-authors in .

"Stage IV (distant metastasis, DLNM excluded) breast cancer remains a virtually incurable disease, with the main goals of treatment being prolongation of survival and palliation of symptoms," the authors noted in their discussion of the findings. "In the present cohort study, we found that patients with DLNM showed comparable survival with patients who had ISLM in any subtype."

Noting that lymph node status is a "paramount factor" in breast cancer staging, the authors of an agreed that a reassessment of DLNM in breast cancer is appropriate. They also pointed out that ISLM are currently classified as stage III disease, whereas contralateral axillary lymph node metastases are classified as stage IV, compared with distant nodal involvement at other sites.

"Owing to the fact that lymph node metastases of several sites are now redefined as locoregional instead of distant disease, is it necessary to reconsider DLNM as a local disease as well?" wrote Yutian Zou, MD, of Sun Yat-sen University Cancer Center in Guangzhou, China, and co-authors. "Fortuitously, this cohort study provides critical evidence. The results showed that locoregional treatments for ISLM, which is staged as IIIC, were also effective for DLNM."

"Overall, it indicates that more locoregional treatments should be considered for patients with DLNM, which may further improve the OS rate and prognosis of these patients," they added.

The study had its origin in the recognition that advances in systemic therapy, the mainstay for stage IV breast cancer, may render some stage IV disease (such as DLNM) potentially curable, especially for patients with limited metastatic burden and favorable site of involvement, the study authors stated. As an example, they cited the case of ISLM, which had been classified as stage IV disease prior to 2002, when evidence showed and substantially better survival compared with stage IV disease.

Few studies had examined survival among patients with DLNM versus that of patients with ISLM and other stage IV breast cancer. The authors analyzed SEER data for 2,033 patients with breast cancer diagnoses during 2010 through 2014. The analysis focused on three groups of patients: those with ISLM (n=212), DLNM (n=346), or non-DLNM distant metastases (n=1,475). The primary outcomes were OS and BCSS.

The study population had a mean age of 62, and three-fourths of the patients were white. Comparison of 3-year BCSS showed similar results for patients with ISLM and DLNM (HR 0.81, 95% CI 0.52-1.25). In contrast, patients with non-DLNM metastatic disease had a twofold increase in the BCSS hazard versus the other two groups (HR 1.99, 95% CI 1.43-2.78, P<0.001).

The 3-year OS rate numerically favored the patients with DLNM versus those with ISLM (62.67% vs 53.46%, P=0.09) and was significantly worse for patients with non-DLNM distant metastases (38.21%; HR 1.79, 95% CI 1.35-2.38, P<0.001).

For patients with DLNM, primary surgery was associated with significantly better OS (HR 0.21, 95% CI 0.12-0.39, P<0.001), as was radiotherapy (HR 0.46, 95% CI 0.25-0.87, P=0.02).

"This cohort study is the first, to our knowledge, to give direct evidence from a large sample size that breast cancer with DLNM may be a curable disease, similar to N3c disease, with a significantly better prognosis than other types of stage IV disease (DLNM excluded)," the study authors concluded. "Locoregional treatment was associated with significantly improved survival for patients with DLNM. Our findings suggest that DLNM of breast cancer may be a regional disease, not a metastatic disease, and it is necessary to reassess the role of lymph node metastases of breast cancer."

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