RESUMO
Intravenous bisphosphonate therapy is used to prevent fractures in the management of bone metastasis. However, it may induce renal damage. We herein report an 81-year-old woman with Fanconi syndrome and osteomalacia who had been diagnosed with metastatic breast cancer and received treatment with zolendronate for over 5 years. Her bone markers normalized after switching zolendronate to denosmab and starting vitamin D and mineral supplementation. This case shows that chronic renal damage induced by zolendronate can cause osteomalacia. In patients with intravenous zolendronate therapy, close monitoring of renal and bone markers is needed, even under long-term therapy.
Assuntos
Anemia de Fanconi , Síndrome de Fanconi , Hipofosfatemia , Osteomalacia , Feminino , Humanos , Idoso de 80 Anos ou mais , Ácido Zoledrônico/efeitos adversos , Síndrome de Fanconi/induzido quimicamente , Síndrome de Fanconi/diagnóstico , Síndrome de Fanconi/complicações , Osteomalacia/etiologia , Difosfonatos/efeitos adversos , Anemia de Fanconi/complicações , Hipofosfatemia/diagnósticoRESUMO
BACKGROUND: Circulating tumor DNA (ctDNA) within a liquid biopsy is a promising marker for genotyping metastatic tumors. MATERIALS AND METHODS: We performed next generation whole exon sequencing of TP53 and PIK3CA genes, which are the 2 most common genetic alterations in breast cancer, in plasma DNA (pDNA) of 17 metastatic breast cancer (MBC) patients and in tumor DNA (tDNA) from their primary tumors. RESULTS: We identified 11 mutations (6 in TP53 and 5 in PIK3CA) in tDNA from 8 patients (47%) and 13 mutations (6 in TP53 and 7 in PIK3CA) in pDNA from 7 patients (41%). Six mutations in pDNA were also identified in tDNA but seven were not. Six MBC patients with TP53 and/or PIK3CA mutations in pDNA had a significantly worse survival rate (P < .05) after recurrence than that of the other 8 MBC patients without these mutations. Carcinoembryonic antigen and cancer antigen 15-3 levels did not correlate with prognosis (P = .675 and P = .877, respectively). CONCLUSION: These results suggest that mutations in ctDNA can be detected with next generation sequencing in MBC patients and could be a more useful prognostic factor for survival after recurrence than conventional tumor markers.
Assuntos
Neoplasias da Mama/genética , DNA de Neoplasias/genética , Recidiva Local de Neoplasia/genética , Fosfatidilinositol 3-Quinases/genética , Proteína Supressora de Tumor p53/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Biópsia/métodos , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Classe I de Fosfatidilinositol 3-Quinases , DNA de Neoplasias/sangue , Éxons/genética , Feminino , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia/mortalidade , Prognóstico , Análise de Sequência de DNA/métodosRESUMO
The present study aimed to construct a prediction model for axillary lymph node metastasis (ALNM) using a DNA microarray assay for gene expression in breast tumor tissues. Luminal A breast cancers, diagnosed by PAM50 testing, were analyzed, and a prediction model (genomic nodal index (GNI)) consisting of 292 probe sets for ALNM was constructed in a training set of patients (n=388), and was validated in the first (n=59) and the second (n=103) validation sets. AUCs of ROC were 0.820, 0.717, and 0.749 in the training, first, and second validation sets, respectively. GNI was most significantly associated with ALNM, independently of the other conventional clinicopathological parameters in all cohorts. It is suggested that GNI can be used to identify the patients with a low risk for ALNM so that sentinel lymph node biopsy can be spared safely.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Neoplasias da Mama/secundário , Técnicas de Apoio para a Decisão , Perfilação da Expressão Gênica/métodos , Testes Genéticos/métodos , Análise de Sequência com Séries de Oligonucleotídeos , Biópsia de Linfonodo Sentinela , Neoplasias da Mama/classificação , Neoplasias da Mama/mortalidade , Neoplasias da Mama/cirurgia , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Predisposição Genética para Doença , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Pessoa de Meia-Idade , Análise Multivariada , Nomogramas , Fenótipo , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Procedimentos DesnecessáriosRESUMO
BACKGROUND: The 95-gene classifier (95-GC) can classify patients with estrogen receptor (ER)-positive and node-negative breast cancer into those with low and high risk of relapse with an accuracy similar to that of 21-GC (Oncotype DX). Because 95-GC uses RNA from fresh-frozen (FF) tumor tissues, we herein attempted to develop a gene classifier that is applicable to RNA from formalin-fixed paraffin-embedded (FFPE) tumor tissues. PATIENTS AND METHODS: 25 paired FF and FFPE tumor tissues were subjected to DNA microarray for gene-expression analysis. Of the 95 probes included in the 95-GC, 72 were selected for construction of the gene classifier for FFPE tumor tissues, because the gene expression detected by these 72 probes was well preserved in the FFPE tumor tissues. RESULTS: The 72-GC was constructed with these 72 probes for the training set comprising 549 FF tumor tissues and validated with 434 FF tumor tissues (relapse-free survival at 10 years was 91% for the low-risk and 74% for the high-risk group (P = 3.74 × 10(-7)). The predictive capability of 72-GC for prognosis was found to be comparable to that of 95-GC. The 25 paired FF and FFPE tumor tissues from each of 25 patients were classified into the same risk group by 72-GC for 23 patients (92% concordance). 72-GC using the FFPE tumor tissues showed that the prognosis for the low-risk group was significantly (P = .007) better than for the high-risk group. CONCLUSION: 72-GC is comparable to 95-GC in terms of accuracy of prognosis prediction, and may be effective for FFPE tumor tissues.