RESUMO
Circulating tumor cells (CTCs) are promising biomarkers for diagnosis and therapy in systemic cancer. However, their infrequent and unreliable detection, especially in nonmetastatic cancer, currently impedes the clinical use of CTCs. Because leukapheresis (LA) targets peripheral blood mononuclear cells, which have a similar density to CTCs, and usually involves processing the whole circulating blood, we tested whether LA could substantially increase CTC detection in operable cancer patients. Therefore, we screened LA products generated from up to 25 L of blood per patient in two independent studies, and found that CTCs can be detected in more than 90% of nonmetastatic breast cancer patients. Interestingly, complete white blood cell sampling enabled determining an upper level for total CTC numbers of about 100,000 cells (median, 7,500 CTCs) per patient and identified a correlation of CTC numbers with anatomic disease spread. We further show that diagnostic leukapheresis can be easily combined with the US Food and Drug Administration-approved CellSearch system for standardized enumeration of CTCs. Direct comparison with 7.5 mL of blood revealed a significantly higher CTC frequency in matched LA samples. Finally, genomic single-cell profiling disclosed highly aberrant CTCs as therapy-escaping variants in breast cancer. In conclusion, LA is a clinically safe method that enabled a reliable detection of CTCs at high frequency even in nonmetastatic cancer patients, and might facilitate the routine clinical use of CTCs as in the sense of a liquid biopsy. Combined with technologies for single-cell molecular genetics or cell biology, it may significantly improve prediction of therapy response and monitoring of early systemic cancer.
Assuntos
Biomarcadores Tumorais/sangue , Neoplasias da Mama/diagnóstico , Técnicas e Procedimentos Diagnósticos , Leucaférese/métodos , Células Neoplásicas Circulantes/patologia , Neoplasias da Mama/sangue , Estudos de Coortes , Hibridização Genômica Comparativa , Feminino , Alemanha , Humanos , Estudos Prospectivos , Estudos Retrospectivos , Estatísticas não ParamétricasRESUMO
BACKGROUND: In the routine work-up of suspect breast lesions, ultrasound-controlled core needle biopsy (CNB) is the most common tool to acquire tissue for histopathologic analysis in a safe, quick and convenient way. Complications are generally rare. The most common complications are hematoma and infection, each with less than 1 in 1000 cases. CASE REPORT: Here, we present a case of a 48-year-old patient who underwent CNB for several lesions that were assessed as Breast Imaging Report and Data System (BI-RADS) IV in breast ultrasound and mammography. In the past, she had had 2 bilateral breast reduction surgeries and 1 open biopsy of a fibroadenoma. Histology revealed a phyllodes tumor. Following this, mastitis occurred which was resistant to common conservative measurements such as intravenous antibiotics over months. Finally, mastectomy was performed, followed by adequate wound healing. CONCLUSIONS: In the presented case, the prolonged course of breast infection after CNB was not as expected. If this occurs, conservative treatment with antibiotics can be initiated. Possible additional risk factors such as diabetes mellitus, steroid therapy, or immunosuppression should be identified. However, in case of missing recovery, wide surgical excision is recommended.
RESUMO
BACKGROUND: Brain metastases in epithelial ovarian cancer (EOC) occur rarely and are associated with a poor prognosis. No significant risk factors have been identified and no evidence-based treatment guidelines are currently available. CASE REPORT: A 56-year-old EOC patient presented with seizure at the Emergency Department eleven days after completion of fourth-line chemotherapy with pegylated liposomal doxorubicin (PLD). A computed tomography (CT) scan revealed multiple metastases. The patient received radiotherapy with a total dose of 30.8 Gy and 8 cycles of paclitaxel resulting in stable disease. Based on the current literature, treatment options are discussed. CONCLUSION: Therapeutic options for brain metastases include radiation, systemic or intrathecal chemotherapy, surgery or a combination regime. Since the effectiveness of systemic chemotherapy remains controversial, current research focuses on developing new anticancer drugs that penetrate the blood-brain barrier in order to prevent and/or treat brain metastases.