Clinical significance of the neutrophil-to-lymphocyte ratio in oligometastatic breast cancer

This study showed that a low NLR was an independent favorable prognostic factor for breast OMD. Although the association between the NLR and prognosis in breast cancer has been reported in multiple studies [12, 13], to the best of our knowledge, this is the first report to show the prognostic significance of the NLR in OMD. A recent systematic review of breast OMD demonstrated that comparing to those without, patients with solitary metastasis, > 24-month interval between primary tumor and OMD, no or limited involved axillary lymph nodes at primary diagnosis, and hormone-receptor positivity were associated with better prognosis [17]. However, the NLR was not considered in that study. Our study results may enable clinicians to better predict the prognosis of patients with OMD by considering the NLR in the prognostic model.

Some studies have suggested that local treatment for metastatic lesions, such as surgery and radiotherapy, improves the survival of patients with OMD [18] The SABR-COMET trial, a phase 2 randomized trial, demonstrated that stereotactic ablative radiotherapy improved the prognosis of patients with OMD from different primary cancers, including breast cancer [19]. The SABR-COMET-3 trial, a phase 3 trial of the same concept, including breast cancer patients with OMD, is currently underway [20]. Some studies have examined outcomes after surgical resection of lung, liver, and brain metastases and suggested good long-term disease control and survival for selected patients [21,22,23,24]. There are also some case–control studies suggesting a survival benefit from surgical resection of metastatic lesions in patients with breast OMD [25,26,27,28,29,30]. However, these studies are retrospective, limited by number of patients, and conducted in highly selective cohorts; thus, a selection bias cannot be avoided. Indeed, the Korean case–control study showed better survival in patients with surgical resection of pulmonary metastases than in patients without surgery, but in the multivariate analysis, surgical resection did not remain an independent prognostic factor [26]. Therefore, it is unclear whether surgery itself contributes to the improved prognosis of patients with OMD. However, these studies do not exclude the possibility that surgical resection of metastatic lesions may provide some survival benefit in highly selected patients with favorable prognosis. A refined prognostic model that can select these patients with favorable prognosis would help to indicate those who would benefit from intensive treatment of curative intent, including surgery. Our results suggest that the addition of the NLR to conventional prognostic factors would be useful in such a prognostic model.

Most studies that examined prognostic factors in OMD focused on tumor-related factors, such as the number of metastatic lesions, metastatic organs, and tumor subtypes. However, it is now clear that host-related factors also affect patient prognosis. In this study, we showed that the NLR at primary diagnosis indicated the survival in patients with breast OMD, probably because it may reflect the host anti-cancer immune status.

Limitations

One of the major limitations in this study was its small number of patients, which resulted partly from it being a single institutional study. Therefore, the survival analysis of this population needs to be interpreted with caution. We are planning a multicenter study with a larger population to confirm the results of this study. Another limitation is that the NLR at the time of recurrence could not be calculated because white blood cell fractions were not measured in all patients at recurrence. However, our result suggested that the NLR at primary cancer impacted survival even after recurrence, indicating the importance of the primary immune status throughout the disease course. The difference in the proportion of patients given adjuvant endocrine therapy between the two groups is another limitation (Table 1). Because female hormones have been reported to affect T-cell proliferation and neutrophil counts [31, 32], adjuvant endocrine therapy may have affected the systemic immune status. To reduce such a bias, we included ER status, which was associated with administration of adjuvant endocrine therapy, in the multivariate analysis, which showed that the NLR was prognostic independent of ER status (Table 3).

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