RESUMEN
OBJECTIVE: The aim: The purpose of this study is to investigate prognostic value of tumor stroma ratio in triple negative breast carcinomas. PATIENTS AND METHODS: Materials and methods: This cohort retrospective study included a total number of 232 previously untreated operational materials with primary stage I-III triple negative breast cancer. The median follow-up period was 3.8 years for overall survival and 3.2 years for disease-free survival. Tumor stroma ratio was evaluated by two pathologists (Kappa coefficient was 0.71 and 0.84, respectively). RESULTS: Results: Kaplan-Meier curves with logrank test statistically significantly showed relationship between tumor stroma ratio and both overall and disease-free survival. The Cox proportional hazards model showed tumor stroma ratio is a strong independent prognostic factor for triple negative breast carcinomas with hazard ratios of 2.11 (p=0.002) for overall survival and 1.83 (p=0.004) for disease-free survival in multivariate analysis. CONCLUSION: Conclusions: Triple negative breast tumors with high stroma ratio have worse overall and disease-free survival compared to low stroma ratio tumors. Investigation of tumor stroma ratio doesn't require any additional costs and slide preparation. It can be added to routine breast cancer investigation to expand knowledge about cancer prognosis.
Asunto(s)
Neoplasias de la Mama , Neoplasias de la Mama Triple Negativas , Biomarcadores de Tumor , Neoplasias de la Mama/patología , Humanos , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Células del Estroma/patología , Neoplasias de la Mama Triple Negativas/patologíaRESUMEN
Breast cancer is the second leading cause of cancer death among women worldwide and besides life style, age and genetic risk factors, exposure to ionizing radiation is known to increase the risk for breast cancer. Further, DNA copy number alterations (CNAs), which can result from radiation-induced double-strand breaks, are frequently occurring in breast cancer cells. We set out to identify a signature of CNAs discriminating breast cancers from radiation-exposed and non-exposed female patients. We analyzed resected breast cancer tissues from 68 exposed female Chernobyl clean-up workers and evacuees and 68 matched non-exposed control patients for CNAs by array comparative genomic hybridization analysis (aCGH). Using a stepwise forward-backward selection approach a non-complex CNA signature, that is, less than ten features, was identified in the training data set, which could be subsequently validated in the validation data set (p value < 0.05). The signature consisted of nine copy number regions located on chromosomal bands 7q11.22-11.23, 7q21.3, 16q24.3, 17q21.31, 20p11.23-11.21, 1p21.1, 2q35, 2q35, 6p22.2. The signature was independent of any clinical characteristics of the patients. In all, we identified a CNA signature that has the potential to allow identification of radiation-associated breast cancer at the individual level.
Asunto(s)
Neoplasias de la Mama/genética , Accidente Nuclear de Chernóbil , Variaciones en el Número de Copia de ADN , Neoplasias Inducidas por Radiación/genética , Exposición a la Radiación/efectos adversos , Adulto , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/patología , Estudios de Cohortes , Hibridación Genómica Comparativa , Femenino , Estudios de Seguimiento , Dosificación de Gen , Genómica , Humanos , Persona de Mediana Edad , Invasividad Neoplásica , Neoplasias Inducidas por Radiación/epidemiología , Neoplasias Inducidas por Radiación/patología , Pronóstico , Curva ROC , Ucrania/epidemiologíaRESUMEN
Ionizing radiation is a well-recognized risk factor for the development of breast cancer. However, it is unknown whether radiation-specific molecular oncogenic mechanisms exist. We investigated post-Chernobyl breast cancers from radiation-exposed female clean-up workers and nonexposed controls for molecular changes. Radiation-associated alterations identified in the discovery cohort (n = 38) were subsequently validated in a second cohort (n = 39). Increased expression of hsa-miR-26b-5p was associated with radiation exposure in both of the cohorts. Moreover, downregulation of the TRPS1 protein, which is a transcriptional target of hsa-miR-26b-5p, was associated with radiation exposure. As TRPS1 overexpression is common in sporadic breast cancer, its observed downregulation in radiation-associated breast cancer warrants clarification of the specific functional role of TRPS1 in the radiation context. For this purpose, the impact of TRPS1 on the transcriptome was characterized in two radiation-transformed breast cell culture models after siRNA-knockdown. Deregulated genes upon TRPS1 knockdown were associated with DNA-repair, cell cycle, mitosis, cell migration, angiogenesis and EMT pathways. Furthermore, we identified the interaction partners of TRPS1 from the transcriptomic correlation networks derived from gene expression data on radiation-transformed breast cell culture models and sporadic breast cancer tissues provided by the TCGA database. The genes correlating with TRPS1 in the radiation-transformed breast cell lines were primarily linked to DNA damage response and chromosome segregation, while the transcriptional interaction partners in the sporadic breast cancers were mostly associated with apoptosis. Thus, upregulation of hsa-miR-26b-5p and downregulation of TRPS1 in radiation-associated breast cancer tissue samples suggests these molecules representing radiation markers in breast cancer.