Background Triple-negative mammary carcinoma (TNBC) is an aggressive breast cancer subtype associated with dismal prognosis. The interaction between the immune system and the cancer cells plays a crucial role in tumor development and progression. However, it is still unclear how each diverse cell of the immune system contributes to the prognosis of patients with breast cancer. In this study, we investigated how the cell composition of the immune cell infiltrated modifies the survival of patients with resected TNBC. Methods Retrospectively, we collected data from 76 patients diagnosed with non-metastatic TNBC with available tissue blocks for tissue micro-array (TMA) construction. The TMA was constructed using two cores from each tumor block. The expression of CD4, CD8, FOXP3, CD20, CD68, CD163, PD-1, PD-L1, PTEN and phospho-STAT1 was determined by immunohistochemistry. Results We observed that the inflammatory infiltrate in TNBC is enriched for M2 macrophages and T lymphocytes (CD4+, CD8+). PD-L1 expression in the stroma was associated with the percentage of TILs (p = 0.018) as, PD-L1 expression in the tumor was associated with the percentage of TILs (p = 0.049). We found a correlation between TILs and PD-L1 expression in stroma cells (p = 0.020) and in tumor cells (p = 0.027). In our cohort, we observed a trend for improved survival associated with higher CD8+ (p = 0.054) and CD4 + (p = 0.082) cell counts, but the results were not statistically significant. Conversely, the expression of PTEN in tumor cells and a low number of FOXP3+ cells in tumor stroma were both associated with improved OS. The CD8 to FOXP3 ratio and the CD4 to FOXP3 ratio were associated with better OS as well, however, only the CD8 to FOXP3 ratio had its prognostic impact confirmed in the METABRIC TNBC cohort. There was no association between PD-L1 expression and OS. Conclusion TNBC tumor microenvironment is enriched for lymphocytes and macrophages. FOXP3 expression and the CD8 to FOXP3 ratio in the tumor stroma as well as the loss of PTEN expression in tumor cells are prognostic factors in non-metastatic TNBC.
e18078 Background: First-line treatment of advanced nonsquamous non-small cell lung cancer (NSCLC) with platinum-based doublets, including pemetrexed (P) or bevacizumab (B), has achieved more than 12 months of survival. At the moment, there are no phase III head-to-head comparisons of these combinations. Methods: We retrospectively analyzed, from 05/2007 to 02/2011, in a single institution, all pts with stage IIIB or IV nonsquamous NSCLC treated with B or P combined with platinum compounds in first-line treatment to determine differences in OS, PFS, ORR and toxicity. We performed multivariate analysis to identify prognostic factors for survival. Results: Of the 82 pts included, 40 pts (48,8%) received carboplatin/paclitaxel or cisplatin/gemcitabine combined with B (BEV group), while 42 pts (51,2%) received cisplatin or carboplatin combined with P (PEM group). BEV had significantly fewer pts with age > 70 years (p=0,01) and CNS metastases (p<0,001) than PEM. Maintenance therapy was administered in 65,0% and 52,4% of pts in BEV and PEM groups, respectively (p=0,17). Significantly more pts in BEV received second-line treatment (72,5% vs. 52,4%; p=0,04) than in PEM, prevailing P as drug of choice (79,3%). ORR (60,0% vs. 35,7%; p=0,04) and median survival (26,4 vs. 16,4 months; p=0,009) were significantly superior for BEV. Median PFS were not different between BEV and PEM (10,5 vs. 7,7 months; p=0,06). In multivariate analysis, ECOG 2 (p=0,005), bone (p=0,01) and adrenal metastases (p=0,005) were independent prognostic factors for worst survival, while treatment with BEV did not reach statistical significance (p=0,07). Grade 3-4 neutropenia (27,5% vs. 9,5%; p=0,03) and neuropathy (17,5% vs. 0%;p=0,005) were more frequent in BEV. Conclusions: First-line treatment of advanced nonsquamous NSCLC patients with platinum-based doublets combined with B resulted in better ORR and higher rate of toxic effects as compared with P-based regimens. ECOG 2, bone and adrenal metastases were independent prognostic factors for poor survival. Although there was a survival benefit at univariate analysis, use of B combination was not an independent prognostic fator.
Introduction: Triple-negative mammary carcinomas (CMTN) correspond to about 15 to 20%, the subtype being more aggressive when compared to the others. The interaction between immune system cells and cancer plays a crucial role in tumor development and progression. However, it is still unclear whether the presence of CD8 cytotoxic lymphocytes provides any prognostic information in breast cancer. Objective: To evaluate the prognostic significance of tumor-associated FOXP3 regulatory T cells (Tregs) and CD8 cytotoxic T lymphocytes (CTLs) in invasive breast carcinomas Method: This is an observational, descriptive retrospective cohort study were evaluated 76 patients diagnosed with non metastatic (stages I, II and III) TNBC. A tissue microarray (TMA) was constructed containing two cores from each tumor block. The expression of CD4, CD8, FOXP3, CD20, CD68, CD163, PD-1, PD-L1, PTEN and phosphoSTAT1 was determined by immunohistochemistry in the TMA. Results: We observed that the inflammatory infiltrate in TNBC is enriched for M2 macrophages and T lymphocytes (CD4+, CD8+ and FOXP3+). In our sample, we observed better survival associated with a higher CD8 + (p = 0.054) and CD4 + (p = 0.082) cell counts, but with no statistical significance in both situations. However, when we analyzed the association of overal survival (OS) with the ratio between the number of CD8 + cells and FOXP3 + (p = 0.007) and CD4 + and FOXP3 + (p = 0.034) and CD4 (p = 0.058) cells, we found that a higher relative proportion of CD8 + or CD4 + lymphocytes in relation to lymphocytes FOXP3 + was associated with an increase in OS. Together, these data suggest that infiltration by T lymphocytes into the tumor microenvironment should exhibit antirumor activity and promote growth control and tumor progression, as opposed to events favoring immunosuppression (regulatory lymphocyte infiltration). The number of FOXP3+ cells and the presence of PTEN staining in tumor cells were associated with OS. Conclusion: We did not observe improvement in survival, with an increase in CD8 and CD4 alone, so we found an improvement in survival, the higher the ratio between CD8 / FOXP3 being statistically significant. The number of FOXP3+ cells and the presence of PTEN staining in tumor cells were associated with OS. Citation Format: Monique C Tavares, Geraldine E Lima, Cristina D Sampaio, Victor P Andrande, Daniel G Gonçalves, Mariana P Macedo, Vladmir C Lima. Ratio of CD8 +/ FOXP3, number of FOXP3 + cells and the presence of PTEN labeling in tumor cells and association with survival in triple negative breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-58.
e21720 Background: Lung cancer has the highest mortality rate among malignant neoplasms worldwide. Most cases present an advanced stages. From the last few years, the target drugs and immunotherapy (IO) have emerged as important therapeutic options in this scenario. In Brazil, in 2018, this disease was responsible for 8.7% of cases of malignant neoplasms in men and 6.2% of cases in women. When looking at data from our state, Rio Grande do Sul, the highest rates in the country are noted, with an estimated rate of 40.22 cases for every 100 thousand men and 20.49 cases for every 100 thousand women. Although the available trials point to significant improvements in the clinical outcomes, the real impact of using such treatments on patients in our community practice, real-world scenario, is unknown. Methods: Through the detailed analysis of the institutional electronic medical record, we included patients with metastatic NSCLC, followed up on an outpatient basis at the Oncology Center of Hospital Moinhos de Vento, who had received at least one dose of nivolumab, pembrolizumab or atezolizumab, either as monotherapy or in combination therapy with chemotherapy, in any line of cancer treatment, in the period from January 2015 to June 2019. Primary endpoint was overall survival (OS) and secondary endpoints were time-to-treatment discontinuation (TTD) and treatment-related toxicity (TRT). Results: 41 patients met criteria. The sample consisted of patients with a mean age at diagnosis of 67.7 years, the majority being male (53.7%), stage IVB disease (53.7%), previously smokers (61%) and with non-squamous NSCLC (75.6%). Central nervous system (CNS) metastases were present in 26.8% of patients. About 51.3% (n = 21) received IO as second line or later treatment. At this group, nivolumab was the main IO (81%). The median OS in the first line (1L) of treatment was not reached while in second line and beyond was 10.0 months (3.4 - 16.5), with no statistical difference (p = 0.071). The median TTD was higher in patients whose received IO at 1L (17.0 months vs 7.0 months, p = 0.045). Pneumonitis was the main toxicity being present in 7.1% of patients. Colitis, thyroiditis and hepatitis were seen in one patient each. Conclusions: in general, we were able to observe that in our real-world scenario, IO is well tolerated, regardless of the treatment line. In addition, OS met the findings of the landmark clinical trials.
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