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1.
PLoS One ; 16(11): e0260124, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34780566

RESUMO

BACKGROUND: Immune checkpoint inhibition is effective in several cancers. Expression of programmed death-ligand 1 (PD-L1) on circulating tumor or immune effector cells could provide insights into selection of patients for immune checkpoint inhibition. METHODS: Whole blood was collected at serial timepoints from metastatic breast cancer patients and healthy donors for circulating tumor cell (CTC) and platelet PD-L1 analysis with a phycoerythrin-labeled anti-human PD-L1 monoclonal antibody (Biolegend clone 29E.2A3) using the CellSearch® assay. CTC PD-L1 was considered positive if detected on at least 1% of the cells; platelet PD-L1 was considered positive if ≥100 platelets per CellSearch frame expressed PD-L1. RESULTS: A total of 207 specimens from 124 metastatic breast cancer patients were collected. 52/124 (42%) samples at timepoint-1 (at or close to time of progressive disease) had ≥5 CTC/7.5ml whole blood. Of those, 21 (40%) had positive CTC PD-L1. In addition, platelet PD-L1 expression was observed in 35/124 (28%) at timepoint-1. Platelet PD-L1 was not detected in more than 70 specimens from 12 healthy donors. Platelet PD-L1 was associated with ≥5 CTC/7.5ml whole blood (p = 0.0002), less likely in patients with higher red blood cell counts (OR = 0.72, p<0.001) and a history of smoking tobacco (OR = 0.76, p<0.001). Platelet PD-L1 staining was not associated with tumor marker status, recent procedures or treatments, platelet-affecting drugs, or CTC PD-L1 expression. CONCLUSION: PD-L1 expression was found in metastatic breast cancer patients on both CTC and platelets in an independent fashion. Inter-patient platelet PD-L1 expression was highly heterogeneous suggesting that it is a biological event associated with cancer in some but not all patients. Taken together, our data suggest that CTC and platelet PD-L1 expression could play a role in predicting which patients should receive immune checkpoint inhibition and as a pharmacodynamics biomarker during treatment.


Assuntos
Antígeno B7-H1/metabolismo , Plaquetas/metabolismo , Neoplasias da Mama/metabolismo , Células Neoplásicas Circulantes/metabolismo , Regulação para Cima , Antígeno B7-H1/genética , Neoplasias da Mama/genética , Estudos de Casos e Controles , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Células MCF-7 , Metástase Neoplásica
2.
CNS Oncol ; 9(3): CNS61, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32945179

RESUMO

Background: The aim of this study was to identify risk factors that may predispose breast cancer patients to the development of CNS metastases. Materials & methods: We conducted a matched case-control study of breast cancer patients treated with surgery with curative intent. A total of 71 cases and 71 controls were analyzed, matched by year of surgery. Results: In our multivariable model, positive lymph node status (odds ratio [OR]: 5.08; CI: 2.04-12.65), the use of neoadjuvant chemotherapy (OR: 6.02; CI: 2.06-17.57) and triple-negative breast cancer (OR: 5.44; CI: 1.99-14.90) were statistically significant predictors of the development of CNS metastases. Conclusion: Women with certain risk factors have an increased odds of developing CNS metastases and evaluation of utility in brain metastases screening should be considered.


Assuntos
Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/terapia , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Neoplasias Encefálicas/metabolismo , Neoplasias da Mama/metabolismo , Estudos de Casos e Controles , Quimiorradioterapia , Terapia Combinada , Feminino , Humanos , Mastectomia , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco
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