This study demonstrated that patients with persistent high NLR and PLR after initial treatment have significantly worse prognosis with regard to late metastasis. In particular, we demonstrated that the NLR and PLR after initial treatment better reflect the prognosis than the NLR and PLR at the time of diagnosis. This result may explain the considerable differences in prognosis in breast cancer patients who have received the same standard treatment.
Tumor development, proliferation, invasion, and metastasis are affected by the host inflammation and immune response in the tumor microenvironment [13-16]. Numerous studies have demonstrated that lymphocytes play a crucial role in tumor immune surveillance [16, 17], and are able to control tumor growth by their cytotoxic activity and induction of apoptosis . Clinical data have shown that an increased density of tumor-infiltrating lymphocytes is associated with favorable prognosis in breast cancer [19, 20]. Meanwhile, neutrophils have been shown to inhibit the immune response by suppressing the cytolytic activity of immune cells, such as lymphocytes, activated T cells, and natural killer cells [21, 22]. Moreover, neutrophils and other cells such as macrophages have been reported to secrete tumor growth-promoting factors, including vascular endothelial growth factor, IL-6, IL-8, and elastases, and thus likely contribute to a pro-tumor microenvironment [23-26]. Furthermore, platelets have been shown to secrete cellular growth factors, including platelet-derived growth factor, vascular endothelial growth factor, and transforming growth factor beta, which could stimulate tumor proliferation and angiogenesis [27-29]. Therefore, having high NLR and PLR, with a high neutrophil or platelet count and/or low lymphocyte count, can result in poor prognosis of multiple cancers.
A recent meta- analysis examining 100 studies demonstrated that a high NLR is associated with adverse survival in many solid tumors . Similarly, in a meta-analysis of breast cancer, a high NLR was found to be associated with an adverse overall survival and disease-free survival, with a greater association with disease-specific outcome in estrogen receptor and HER-2 negative disease. Furthermore, the PLR in breast cancer highly correlated with clinicopathologic characteristics and was associated with poor prognosis .
With well-established prognostic factors, the estimation of risk development of a systemic disease following the treatment for breast cancer can be made possible. Known prognostic factors include histologic subtype of breast cancer, tumor grade, tumor size, involvement of skin or chest wall, extent of involvement of regional lymph nodes, hormone receptor status, and HER-2 status. However, due to the complex nature of breast cancer, the progression and prognosis according to time have been variable and difficult to predict adequately. Recently, a number of proven multigene array expression profiles, such as Oncotype Dx® and Pam-50 ror®, have yielded better predictive power of late recurrence; however, these tests are expensive and inaccessible to most patients [30-32].
In recent years, considerable effort and resources have been used in developing biomarkers, which can help to tailor therapy for cancer patients. A small number of patients have persistent poor clinical outcome irrespective of treatment with standard therapy; thus, finding a marker that predicts the prognosis of these patients remains a valuable research subject. Changes in blood inflammatory markers might be useful to predict the post-treatment prognosis and tailor the therapy after. Previous small studies have shown that chemotherapy can normalize an elevated NLR early after the introduction of treatment and that patients with a normalized NLR may have improved outcome in advanced colorectal, urothelial, and biliary cancer [33-35]. Thus, it is considered that the prognostic role of the NLR might still be relevant for the evaluation of the early effects of systemic therapy. Further, in patients with metastatic breast cancer, high NLR was found to be factor related to low responsiveness to eriburin-based treatment . Recently inflammatory markers were also reported as important prognostic markers not only in systemic therapy but also in immune therapy. In study, which perfromed in 90 patients who received immunotherapy based treatment regimens, elevated baseline and early increases in NLR and PLR values were strongly associated with poor clinical outcomes in advanced cancer patients. (37)
In most cancer patients, a routine blood test is widely used as a traditional examination test at the time of diagnosis and follow-up periods. The results of our study confirmed that observing the process of continuous change, as well as the initial NLR or PLR, can also be an important indicator for predicting the prognosis of the patient. Indeed, a recent study demonstrated that patients with a high NLR approximately 5 years after the initial diagnosis had significantly worse breast cancer-free survival with late recurrence (HR, 1.448; 95% CI, 1.168–1.795; p < 0.001). Furthermore, it was shown that the NLR obtained after the completion of primary treatment can predict later recurrence in breast cancer patients .
Our study has several limitations. First, the retrospective nature of the study necessitates prospective validation of the prognostic effect. Second, this study analyzed the NLR and PLR values between 2 and 3 years, but further research is needed to determine whether the prognosis varies after this period, depending on the pattern of continuous change in long term. Third, we only analyzed our hospital data, which included a relatively small number of enrolled patients and had an insufficient follow-up period.