Breast Cancer Distant LN Metastases ‘May Be A Regional Disease’

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: Women with distant lymph node metastases (DLNM) of breast cancer have survival outcomes that are closer to patients with ipsilateral supraclavicular lymph node metastases (ISLNM) than to patients with other forms of distant disease, research suggests. 

“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”, say Wenbin Zhou and Shui Wang, from The First Affiliated Hospital with Nanjing Medical University in China, and co-authors. 

The team gathered data from the US Surveillance, Epidemiology and End Results database for 2033 patients diagnosed with breast cancer between 2010 and 2014, of whom 17.0% had DLNM, 10.4% had ISLM and 72.6% had distant metastases not including DLNM. 

The 3-year breast cancer-specific survival (BCSS) rates in the DLNM, ISLNM and distant metastases were 64.54%, 63.24% and 41.20%, respectively, with corresponding 3-year overall survival (OS) rates of 62.67%, 53.46% and 38.21%. 

At a median 27 months of follow-up, there was no significant difference in either BCSS or OS between women with DLNM and those with ISLNM, the researchers report in JAMA Network Open.  

By contrast, women with distant metastases excluding DLNM were a significant 2.17 times more likely to die from breast cancer and 1.90 times more likely to die from any cause than those with ISLM. 

And after adjusting for age, race/ethnicity and breast cancer stage, histology and molecular subtype, patients with DLNM continued to show comparable BCSS and OS to those of the ISLNM patients, whereas patients with distant metastases excluding DLNM had significantly poorer survival, with hazard ratios (HRs) of 1.99 and 1.79, respectively.  

The researchers also investigated the impact of locoregional treatment among the 346 patients with DLNM, of whom 55.8% underwent surgery on their primary tumour, 15.0% distant LN surgery and 36.7% radiotherapy. 

In Cox proportional hazards model analysis, patients who underwent primary surgery had significantly better BCSS and OS than those who did not (HR=0.17 and 0.21, respectively), while receipt of radiotherapy was associated with a significant OS benefit (HR=0.46). 

The researchers note that subgroup analysis indicated a “consistent” BCSS and OS benefit with both primary tumour surgery and radiotherapy in DLNM patients with hormone receptor-positive, HER2-negative and triple-negative breast cancer, whereas women with HER2-positive breast cancer derived only OS benefits from the treatments. 

“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)”, summarise Wenbin Zhou, Shui Wang and co-authors. 

The authors of a linked comment say that “[g]iven the large sample size, results are credible, and lead to considerations on reviewing the current TNM staging for breast cancer.” 

Nevertheless, Yutian Zou, from Sun Yat-sen University Cancer Center in Guangzhou, China, and co-authors note that “selection bias is inevitable” in the study because of differences in baseline characteristics of the three patient cohorts and the absence of information on chemotherapy regimens and radiation dosing. 

The team also highlights that the majority of patients included in the study were White, emphasizing the need for study in other ethnic groups, and that the “short” duration of follow-up may affect final survival outcomes. 

The commentators therefore advise that “more multicenter randomized clinical trials and observational studies with high quality, large sample size, multivariable analysis, and adequate follow-up are required for further validation.” 

References 

Pan H, Wang H, Qian M, et al. Comparison of survival outcomes among patients with breast cancer with distant vs ipsilateral supraclavicular lymph node metastases. JAMA Netw Open 2021;4:e211809. doi:10.1001/jamanetworkopen.2021.1809

Zou Y, Hu X, Deng X. Distant lymph node metastases from breast cancer–Is it time to review TNM cancer staging? JAMA Netw Open 2021;4:e212026. doi:10.1001/jamanetworkopen.2021.2026