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Immune phenotype of patients with stage IV metastatic inflammatory breast cancer.

ABSTRACT: Background: Inflammatory breast cancer (IBC) is a rare but aggressive carcinoma characterized by severe erythema and edema of the breast, with many patients presenting in advanced metastatic disease. The "inflammatory" nature is not due to classic immune-mediated inflammation, but instead results from tumor-mediated blockage of dermal lymphatic ducts. Previous work has shown that expression of PD-L1 on tumor cells can suppress T cell activation in triple-negative (TN) non-IBC breast cancer. In the present work, we investigated immune parameters in peripheral blood of metastatic IBC patients to determine whether cellular components of the immune system are altered, thereby contributing to pathogenesis of the disease. These immune parameters were also compared to PD-1 and PD-L1 expression in IBC tumor biopsies.

Methods: Flow cytometry-based immune phenotyping was performed using fresh peripheral blood from 14 stage IV IBC patients and compared to 11 healthy age-similar control women. Immunohistochemistry for CD20, CD3, PD-1, and PD-L1 was performed on tumor biopsies of these metastatic IBC patients.

Results: IBC patients with Stage IV disease had lymphopenia with significant reductions in circulating T, B, and NK cells. Reductions were observed in all subsets of CD4⁺ T cells, whereas reductions in CD8⁺ T cells were more concentrated in memory subsets. Immature cytokine-producing CD56^bright NK cells expressed higher levels of Fc?RIIIa and cytolytic granule components, suggesting accelerated maturation to cytolytic CD56^dim cells. Immunohistochemical analysis of tumor biopsies demonstrated moderate to high expression of PD-1 in 18.2% of patients and of PD-L1 in 36.4% of patients. Interestingly, a positive correlation was observed between co-expression levels of PD-L1 and PD-1 in tumor biopsies, and higher expression of PD-L1 in tumor biopsies correlated with higher expression of cytolytic granule components in blood CD4⁺ T cells and CD56^dim NK cells, and higher numbers of CD8⁺ effector memory T cells in peripheral blood. PD-1 expression in tumor also correlated with increased infiltration of CD20⁺ B cells in the tumor.

Conclusions: Our results suggest that while lymphocyte populations are severely compromised in stage IV IBC patients, an immune response toward the tumor had occurred in some patients, providing biological rationale to evaluate PD-1/PD-L1 immunotherapies for IBC.

SUBMITTER: Fernandez SV

PROVIDER: S-EPMC7709446 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Immune phenotype of patients with stage IV metastatic inflammatory breast cancer.

Fernandez Sandra V SV MacFarlane Alexander W AW Jillab Mowafaq M Arisi Maria F MF Yearley Jennifer J Annamalai Lakshmanan L Gong Yulan Y Cai Kathy Q KQ Alpaugh R Katherine RK Cristofanilli Massimo M Campbell Kerry S KS

Breast cancer research : BCR 20201202 1

<h4>Background</h4>Inflammatory breast cancer (IBC) is a rare but aggressive carcinoma characterized by severe erythema and edema of the breast, with many patients presenting in advanced metastatic disease. The "inflammatory" nature is not due to classic immune-mediated inflammation, but instead results from tumor-mediated blockage of dermal lymphatic ducts. Previous work has shown that expression of PD-L1 on tumor cells can suppress T cell activation in triple-negative (TN) non-IBC breast cance ...[more]

PMID: 33267869

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Project description:Background: The role of surgery and surgery type in de novo stage IV breast cancer (BC) is unclear. Methods: We carried out a retrospective cohort study that included the data of 4,108 individuals with de novo stage IV BC abstracted from SEER (Surveillance, Epidemiology, and End Results) data resource from 2010 to 2015. The patients were stratified into the non-surgery group, breast-conserving (BCS) surgery group, and mastectomy group. Inverse probability propensity score weighting (IPTW) was then used to balance clinicopathologic factors. Overall survival (OS), as well as the breast cancer-specific survival (BCSS), was assessed in the three groups using Kaplan-Meier analysis and COX model. Subgroups were stratified by metastatic sites for analysis. Results: Of the 4,108 patients, 48.5% received surgery and were stratified into the BCS group (574 cases) and mastectomy group (1,419 cases). After IPTW balance demographic and clinicopathologic factors, BCS and mastectomy groups had better OS (BCS group: HR, 0.61; 95% CI: 0.49-0.75; mastectomy group: HR, 0.7; 95% CI: 0.63-0.79) and BCSS (BCS group: HR, 0.6; 95% CI, 0.47-0.75; mastectomy group: HR, 0.71; 95% CI, 0.63-0.81) than the non-therapy group. Subgroup analyses revealed that BCS, rather than mastectomy, was linked to better OS (HR, 0.66; 95% CI: 0.48-0.91) and BCSS (HR, 0.63; 95% CI: 0.45-0.89) for patients with bone-only metastasis. For patients with viscera metastasis or bone+viscera metastases, BCS achieved similar OS (viscera metastasis: HR, 1.05; 95% CI: 0.74-1.48; bone+viscera metastases: HR, 1.01; 95% CI: 0.64-1.61) and BCSS (viscera metastasis: HR, 0.94; 95% CI: 0.64-1.38; bone+viscera metastases: HR, 1.06; 95% CI: 0.66-1.73) in contrast with mastectomy. Conclusions: Local surgery for patients with distant metastasis (DS) exhibited a remarkable survival advantage in contrast with non-operative management. BCS may have more survival benefits for patients with de novo stage IV BC with bone-only metastasis than other metastatic sites. Decisions on de novo stage IV BC primary surgery should be tailored to the metastatic pattern.

Project description:BACKGROUND The early death of patients is a global cancer issue. We aimed to identify the risk factors for early death in stage IV breast cancer. Predictive nomograms for early death evaluation were generated based on the risk factors. MATERIAL AND METHODS Based on the Surveillance, Epidemiology, and End Results (SEER) database, patients diagnosed with IV breast cancer were selected. The risk factors for early death (survival time ?1 year) were identified using logistic regression model analysis. Predictive nomograms were constructed and internal validation was performed. RESULTS A total of 5998 (32.6%) breast cancer patients were diagnosed as early death in the construction cohort. Age older than 50 years, unmarried status, black race, uninsured status, triple-negative type, grade (II and III), tumor size >5 cm, and metastasis to lung, liver, and brain were risk factors for total early death, while Luminal B subtype, N1 stage, and surgical interventions were associated with lower risk of early death. As for cancer-specific and non-cancer-specific early death, several factors were not consistent between the 2 groups. Nomograms for all-cause, cancer-specific, and non-cancer-specific early death were constructed. The calibration curve showed satisfactory agreement. The areas under the ROC curve (AUC) were 78.3% (95% CI: 77.7-78.9%), 75.8% (75.1-76.4%), and 72.3% (71.6-72.9%), respectively. In the validation cohort, a total of 689 (19.3%) patients were diagnosed as early death and the calibration curve showed satisfactory agreement. The AUCs of the all-cause, cancer-specific, and non-cancer-specific early death prediction were 74.0% (95% CI: 72.5-75.4%), 73.5% (72.0-74.9%), and 68.6% (67.0-70.1%), respectively. CONCLUSIONS Nomograms were generated to predict early death, with good calibration and discrimination. The predictive model can provide a reference for identifying cases with high risk of early death among stage IV breast cancer patients and play an auxiliary role in guiding individual treatment.

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Immune phenotype of patients with stage IV metastatic inflammatory breast cancer.

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Immune phenotype of patients with stage IV metastatic inflammatory breast cancer.

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