RESUMO
Breast cancer is a heterogeneous disease. Tumor cells and associated healthy cells form ecosystems that determine disease progression and response to therapy. To characterize features of breast cancer ecosystems and their associations with clinical data, we analyzed 144 human breast tumor and 50 non-tumor tissue samples using mass cytometry. The expression of 73 proteins in 26 million cells was evaluated using tumor and immune cell-centric antibody panels. Tumors displayed individuality in tumor cell composition, including phenotypic abnormalities and phenotype dominance. Relationship analyses between tumor and immune cells revealed characteristics of ecosystems related to immunosuppression and poor prognosis. High frequencies of PD-L1+ tumor-associated macrophages and exhausted T cells were found in high-grade ER+ and ER- tumors. This large-scale, single-cell atlas deepens our understanding of breast tumor ecosystems and suggests that ecosystem-based patient classification will facilitate identification of individuals for precision medicine approaches targeting the tumor and its immunoenvironment.
Assuntos
Neoplasias da Mama , Tolerância Imunológica , Linfócitos do Interstício Tumoral , Macrófagos , Microambiente Tumoral/imunologia , Antígeno B7-H1/imunologia , Neoplasias da Mama/imunologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Intervalo Livre de Doença , Feminino , Humanos , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/patologia , Macrófagos/imunologia , Macrófagos/patologia , Proteínas de Neoplasias/imunologia , Taxa de SobrevidaRESUMO
BACKGROUND: Several studies and a meta-analysis showed that fibrin sealant patches reduced lymphatic drainage after various lymphadenectomy procedures. Our goal was to investigate the impact of these patches on drainage after axillary dissection for breast cancer. METHODS: In a phase III superiority trial, we randomized patients undergoing breast-conserving surgery at 14 Swiss sites to receive versus not receive three large TachoSil® patches in the dissected axilla. Axillary drains were inserted in all patients. Patients and investigators assessing outcomes were blinded to group assignment. The primary endpoint was total volume of drainage. RESULTS: Between March 2015 and December 2016, 142 patients were randomized (72 with TachoSil® and 70 without). Mean total volume of drainage in the control group was 703 ml [95% confidence interval (CI) 512-895 ml]. Application of TachoSil® did not significantly reduce the total volume of axillary drainage [mean difference (MD) -110 ml, 95% CI -316 to 94, p = 0.30]. A total of eight secondary endpoints related to drainage, morbidity, and quality of life were not improved by use of TachoSil®. The mean total cost per patient did not differ significantly between the groups [34,253 Swiss Francs (95% CI 32,625-35,880) with TachoSil® and 33,365 Swiss Francs (95% CI 31,771-34,961) without, p = 0.584]. In the TachoSil® group, length of stay was longer (MD 1 day, 95% CI 0.3-1.7, p = 0.009), and improvement of pain was faster, although the latter difference was not significant [2 days (95% CI 1-4) vs. 5.5 days (95% CI 2-11); p = 0.2]. CONCLUSIONS: TachoSil® reduced drainage after axillary dissection for breast cancer neither significantly nor relevantly.
