RESUMEN
PURPOSE: Myelosuppressive chemotherapy-induced neutropenia (CIN) remains a major limitation of cancer treatment efficacy, necessitating very expensive supportive care. Lithium carbonate, an inexpensive drug, can increase the number of neutrophils, possibly providing an efficacious and cost-effective alternative for treating CIN. The aim of this study was to determine whether lithium therapy can attenuate chemotherapy-induced neutropenia and leukopenia in breast cancer patients. METHODS: A total of 50 breast cancer patients were enrolled in this prospective, interventional, randomized, controlled, and single-blind study. The patients were divided into two groups: a control group (group 1, N = 25 patients) and a lithium-treated (treatment) group (group 2, N = 25 patients). Group 1 patients were further subclassified into a non-neutropenic control group (N = 16) and a neutropenic control (N = 9) based on the subsequent development of severe neutropenia, or not. The control group received 4 cycles of doxorubicin or epirubicin plus cyclophosphamide followed by 2 cycles of paclitaxel. The treatment group received the same regimen as the control group as well as oral lithium carbonate throughout the chemotherapy cycles. RESULTS: The results showed that the absolute neutrophil count (ANC) was increased in the lithium-treated group, while it was markedly reduced in both the non-neutropenic and neutropenic control groups (by 55.56% and 65.42% post-4 chemotherapy cycles, and by 19.57% and 39.90% post-6 cycles, respectively). The same pattern of alterations was observed for the total white blood cell count in both the control and treatment groups. In addition, the incidence and period prevalence were greatly reduced in the lithium-treated group compared to non-neutropenic and neutropenic control groups. CONCLUSION: Lithium therapy ameliorated chemotherapy-induced leukopenia and neutropenia in breast cancer patients. This may provide a new strategy for cost-effective treatment of CIN, particularly in Egyptian cancer patients.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de la Mama , Ciclofosfamida , Carbonato de Litio , Neutropenia , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neutropenia/inducido químicamente , Estudios Prospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Persona de Mediana Edad , Egipto , Carbonato de Litio/uso terapéutico , Carbonato de Litio/efectos adversos , Adulto , Método Simple Ciego , Ciclofosfamida/efectos adversos , Doxorrubicina/efectos adversos , Epirrubicina/efectos adversos , Epirrubicina/administración & dosificación , Leucopenia/inducido químicamente , Paclitaxel/efectos adversos , Paclitaxel/administración & dosificación , Neutrófilos/efectos de los fármacosRESUMEN
AIMS: Circulating long non-coding RNAs (lncRNAs) have proven to be useful non-invasive tools for diagnosis of various cancers. FAM83H antisense RNA 1 (FAM83H-AS1) and lncRNA activated by TGF ß (lncRNA-ATB) are two lncRNAs that have been shown to play an important role in different cancer types including breast cancer. The primary aim of our study was to investigate the potential role of serum FAM83H-AS1 and lncRNA-ATB as diagnostic/prognostic markers for breast cancer patients. MAIN METHODS: Serum expression levels of FAM83H-AS1 and lncRNA-ATB were analyzed in 90 breast cancer patients and 30 age- and sex-matched healthy controls using RT-qPCR. KEY FINDINGS: We found that FAM83H-AS1 and lncRNA-ATB were significantly overexpressed in sera of breast cancer patients compared to controls (p = 0.000 for both). Analysis of receiver operating characteristic curve demonstrated that lncRNA-ATB had a higher area under curve (AUC) value than the conventional tumor marker cancer antigen 15-3 (CA15-3) (AUC: 0.844, p = 0.000 versus 0.738, p = 0.002) for early diagnosis of breast cancer in patients with stage I-II. On the other hand, FAM83H-AS1 showed a significant correlation with tumor-node metastasis (TNM) stages, large tumor size and lymph node metastasis, suggesting a prognostic rather than diagnostic value. SIGNIFICANCE: This is the first study to demonstrate that serum lncRNA-ATB could be used as a non-invasive diagnostic marker for early stages of breast cancer. Furthermore, serum FAM83H-AS1 has a potential ability for monitoring of progression and staging of breast cancer.