Dataset Information

Outcomes of non-metastatic triple negative breast cancers: Real-world data from a large Indian cohort.

ABSTRACT:

Background

Triple negative Breast tumor (TNBC) is an aggressive tumor with sparse data worldwide.

Methods

We analyzed non-metastatic TNBC from 2013 to 2019 for demographics, practice patterns, and survival by the Kaplan Meir method. Prognostic factors for OS and DFS were evaluated using Cox Proportional Hazard model estimator for univariate and multivariable analysis after checking for collinearity among the variables.

Results

There were 1297 patients with median age of 38 years; 41 (33.3%) among 123 tested were BRCA-positives. Among these 593 (45.7%) had stage III disease, 1279 (98.6%) were grade III, 165 (13.0%) had peri-nodal extension (PNE), 212 (16.0%) lympho-vascular invasion (LVI), and 21 (1.6%) were metaplastic; 1256 (96.8%) received chemotherapy including 820 (63.2%) neoadjuvant with 306 (40.0%) pCR. Grade ≥3 toxicities occurred in 155 (12.4%) including two deaths and 3 s-primaries. 1234 (95.2%) underwent surgery [722 (55.7%) breast conservations] and 1034 (79.7%) received radiotherapy. At a median follow-up of 54 months, median disease-free (DFS) was 92.2 months and overall survival (OS) was not reached. 5-year estimated DFS and OS was 65.9% and 80.3%. There were 259 (20.0%) failures; predominantly distant (204, 15.7%) - lung (51%), liver (31.8%). In multivariate analysis presence of LVI (HR-2.00, p-0.003), PNE (HR-2.09 p-0.003), older age (HR-1.03, p-0.002) and stage III disease (HR-4.89, p-0.027), were associated with poor OS.

Conclusion

Relatively large contemporary data of non-metastatic TNBC confirms aggressive biology and predominant advanced stage presentation which adversely affects outcomes. The data strongly indicate the unmet need for early detection to optimize care.

SUBMITTER: Bajpai J

PROVIDER: S-EPMC8942859 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Publications

Outcomes of non-metastatic triple negative breast cancers: Real-world data from a large Indian cohort.

Bajpai Jyoti J Kashyap Lakhan L Vallathol Dilip Harindran DH Das Ankita A Singh Maneesh M Pathak Rima R Rath Sushmita S Sekar Anbarasan A Mohanta Subham S Reddy Asha A Joshi Shalaka S Nandhana Ravindra R Ravind Rahul R Wadasadawala Tabassum T Nair Nita N Ghosh Jaya J Parmar Vani V Gulia Seema S Desai Sangeeta S Shet Tanuja T Thakur Meenakshi M Patil Asawari A Sarin Rajiv R Gupta Sudeep S Badwe Rajendra R

Breast (Edinburgh, Scotland) 20220319

<h4>Background</h4>Triple negative Breast tumor (TNBC) is an aggressive tumor with sparse data worldwide.<h4>Methods</h4>We analyzed non-metastatic TNBC from 2013 to 2019 for demographics, practice patterns, and survival by the Kaplan Meir method. Prognostic factors for OS and DFS were evaluated using Cox Proportional Hazard model estimator for univariate and multivariable analysis after checking for collinearity among the variables.<h4>Results</h4>There were 1297 patients with median age of 38 ...[more]

PMID: 35334242

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Project description:BackgroundAlthough triple-negative breast cancer (TNBC) is associated with an increased risk of recurrence and metastasis, the molecular mechanisms underlying metastasis in TNBC remain unknown. To identify transcriptional changes and genes regulating metastatic progression in TNBC, we compared the transcriptomic profiles of primary and matched metastatic tumors using massively parallel RNA sequencing.MethodsWe performed gene expression profiling using formalin-fixed paraffin-embedded (FFPE) TNBC tissues of patients from two cohorts: the Zurich cohort (n = 31) and the Stavanger cohort (n = 5). Among the 31 patients in the Zurich cohort, 18 had primary TNBC tumors that did not metastasize, and 13 had primary tumors that metastasized (11 paired primary and locoregional recurrences). The Stavanger cohort included five matched primary and metastatic TNBC tumors. Significantly differentially expressed genes (DEGs; absolute fold change ≥2, p < 0.05) were identified and subjected to functional analyses. We investigated if there was any overlap between DEGs from both the cohorts with epithelial-to-mesenchymal-to-amoeboid transition (EMAT) gene signature. xCell was used to estimate relative fractions of 64 immune and stromal cell types in each RNA-seq sample.ResultsIn the Zurich cohort, we identified 1624 DEGs between primary TNBC tumors and matched metastatic lesions. xCell analysis revealed a significantly higher immune scores for metastatic lesions compared to paired primary tumors in the Zurich cohort. We also found significant upregulation of three MammaPrint signature genes (HRASLS, TGFB3 and RASSF7) in primary tumors that metastasized compared to primary tumors that remained metastasis-free. In the Stavanger cohort, we identified 818 DEGs between primary tumors and matched metastatic lesions. No significant differences in xCell immune scores were observed. We found that 21 and 14 DEGs from Zurich and Stavanger cohort, respectively, overlapped with the EMAT gene signature. In both cohorts, genes belonging to the MMP, FGF, and PDGFR families were upregulated in primary tumors compared to matched metastatic lesions.ConclusionsOur results suggest that distinct gene expression patterns exist between primary TNBCs and matched metastatic tumors. Further studies are warranted to explore whether these discrete expression profiles underlie or result from disease status.

Project description:Introduction:Ex vivo-expanded natural killer (NK) cells are a potential candidate for cancer immunotherapy based on high cytotoxicity against malignant tumor cells. However, a limited understanding of the migration of activated NK cells toward solid tumors is a critical dilemma in the development of effective and adoptive NK cell-based immunotherapy. Methods:Ex vivo-expanded NK cells from healthy donors were stained with near-infrared fluorophores at different concentrations. NK cell proliferation and cytotoxicity were assessed using a WST-8 assay, while the expression levels of surface molecules were analyzed by flow cytometry. To investigate the biodistribution of NK cells in both normal and tumor-bearing NSG mice, NK cells labeled with ESNF13 were subjected to NIR fluorescence imaging using the Mini-FLARE imaging system. Finally, mice were sacrificed and histopathological tests were performed in resected organs. Results:The signal intensity of ESNF-stained NK cells was long-lasting at 72 h using concentrations as low as 0.04 µM. At a low dose range, ESNF13 did not affect NK cell purity, expression levels of surface receptors, or cytotoxic functions against MDA-MB-231 cancer cells. Ex vivo-expanded NK cells labeled with ESNF13 had a 4-h biodistribution in non-tumor-bearing NSG mice that mainly localized to the lungs immediately after injection and then fully migrated to the kidney after 4 h. In an MDA-MB-231 tumor-bearing NSG mice with extensive metastasis in both lungs, the fluorescence signal was dominant in both lungs and steady at 1, 2, and 4 h post-injection. In a early phase of tumor progression, administered NK cell migrated to the lungs and tumor sites within 30 min post-injection, the signal dominated the tumor site after 1 h, and remained steady at 4 h. Conclusion:Optical imaging with NIR fluorophore ESNF13 is a highly sensitive, applicable, and inexpensive method for the real-time tracking of ex vivo-expanded NK cells both in vitro and in vivo. Administered NK cells had different patterns of NK cell distribution and accumulation to the tumor site according to tumor progression in triple-negative breast cancer xenograft models.

Dataset Information

Outcomes of non-metastatic triple negative breast cancers: Real-world data from a large Indian cohort.

Background

Methods

Results

Conclusion

Publications

Outcomes of non-metastatic triple negative breast cancers: Real-world data from a large Indian cohort.

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