The role of low lymphocytes and circulating tumor cells as prognostic factors in metastatic breast cancer

The aim of this study was to asses the prognostic significance of lymphocytopenia (very low lymphocytes-cells involved in the immune response), circulating tumor cell (CTC) count in patients with metastatic breast cancer (MBC). Lymphocytopenia and CTC measurement seem to be independent factors for predicting overall survival in patients with MBC.

Lymphocytopenia (low immune cells) is a predictor of chemotherapy efficiency in advanced cancer due to blood toxicity. It is also proven to be an independent prognostic factor for overall survival (OS – survival at the end of surveillance) and progression-free survival (PFS – survival without tumor progression), especially a value lower than 1000/μL.

CTC detection, persistence and elevation in the blood of patients with MBC are associated with a worse prognosis. Also, a high number of CTCs is correlated with extensive bone metastases (>2 lesions).

This study was conducted between 2004 and 2008 on 195 patients with MBC. The patients were evaluated based on estrogen receptor status (cancer cells may receive signals from estrogen that could induce their growth – estrogen receptor positive/negative). Other aspects considered were HER2 status (factor involved in tumor growth), lymphocytopenia, CTCs per 7.5 mL of blood (less than 5/ more than 5), first-line chemotherapy or later lines of therapy and extensive bone metastases (cancer spread to the bones).

The results showed that 40% of the patients were newly diagnosed with MBC whereas 60% had received previous treatment for MBC. 47% of the patients had ≥5 CTCs per 7.5 mL of blood. 29% of the cases registered lymphocytopenia  <1000/μL, and 4% had <400/μL. 60% of patients had previously received first-line therapy and were undergoing later line therapy at the time of the study. Statistical analysis revealed that being estrogen receptor negative, having ≥5 CTCs per 7.5 mL of blood, lymphocytopenia and later line therapy were found to be predictive of PFS. The median PFS and OS for all patients included in the study were 7 and 27 months respectively.

Lymphocytopenia and having over 5 CTCs per 7.5 mL of blood were found to be independent prognostic factors for PFS and OS in patients with MBC.

Lymphocitopenia may promote tumor progression. Further studies are needed to better understand the mechanisms involved in lymphocitopenia and the release of CTC from the primary tumor and the consequences on patient outcomes.