triple negative breast carcinoma
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Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3586
Author(s):  
Pedro Adolpho de Menezes Pacheco Serio ◽  
Gláucia Fernanda de Lima Pereira ◽  
Maria Lucia Hirata Katayama ◽  
Rosimeire Aparecida Roela ◽  
Simone Maistro ◽  
...  

Background: Triple-negative breast cancer (TNBC) and High-Grade Serous Ovarian Cancer (HGSOC) are aggressive malignancies that share similarities; however, different ages of onset may reflect distinct tumor behaviors. Thus, our aim was to compare somatic mutations in potential driver genes in 109 TNBC and 81 HGSOC from young (Y ≤ 40 years) and elderly (E ≥ 75 years) patients. Methods: Open access mutational data (WGS or WES) were collected for TNBC and HGSOC patients. Potential driver genes were those that were present in the Cancer Gene Census—CGC, the Candidate Cancer Gene Database—CCGD, or OncoKB and those that were considered pathogenic in variant effect prediction tools. Results: Mutational signature 3 (homologous repair defects) was the only gene that was represented in all four subgroups. The median number of mutated CGCs per sample was similar in HGSOC (Y:3 vs. E:4), but it was higher in elderly TNBC than it was in young TNBC (Y:3 vs. E:6). At least 90% of the samples from TNBC and HGSOC from Y and E patients presented at least one known affected TSG. Besides TP53, which was mutated in 67–83% of the samples, the affected TSG in TP53 wild-type samples were NF1 (yHGSOC and yTNBC), PHF6 (eHGSOC and yTNBC), PTEN, PIK3R1 and ZHFX3 (yTNBC), KMT2C, ARID1B, TBX3, and ATM (eTNBC). A few samples only presented one affected oncogene (but no TSG): KRAS and TSHR in eHGSOC and RAC1 and PREX2 (a regulator of RAC1) in yTNBC. At least ⅔ of the tumors presented mutated oncogenes associated with tumor suppressor genes; the Ras and/or PIK3CA signaling pathways were altered in 15% HGSOC and 20–35% TNBC (Y vs. E); DNA repair genes were mutated in 19–33% of the HGSOC tumors but were more frequently mutated in E-TNBC (56%). However, in HGSOC, 9.5% and 3.3% of the young and elderly patients, respectively, did not present any tumors with an affected CGC nor did 4.65% and none of the young and elderly TNBC patients. Conclusion: Most HGSOC and TNBC from young and elderly patients present an affected TSG, mainly TP53, as well as mutational signature 3; however, a few tumors only present an affected oncogene or no affected cancer-causing genes.


2021 ◽  
Vol 1 (1) ◽  
pp. 45-52
Author(s):  
Kit Cheng Wai ◽  
Kin Iong Chan ◽  
Hong Ting Vong ◽  
Xue Yun Zhong ◽  
Jian Ming Wen

2021 ◽  
Vol 8 ◽  
Author(s):  
Shafei Wu ◽  
Xiaohua Shi ◽  
Xinyu Ren ◽  
Kaimi Li ◽  
Junyi Pang ◽  
...  

Triple-negative breast carcinoma (TNBC) is an aggressive disease that has a poor prognosis since it lacks effective treatment methods. Neurotrophic tyrosine receptor kinase (NTRK) fusion genes are excellent candidates for targeted RTK inhibitor therapies and there are available targeted therapy drugs for the treatment of TRK fusion-positive tumors in a tumor agnostic pattern. Our study was designed to investigate the NTRK gene fusion status in TNBC patients and to determine whether RTK-targeted therapies are suitable for TNBC patients. A total of 305 TNBC patients were enrolled in our study. IHC was employed as a prescreening method, and IHC positive cases were further submitted for evaluation by FISH, RT-PCR, and NGS methods. NTRK IHC was evaluated successfully in 287 of the 305 cases, and there were 32 (11.15%) positive cases. FISH was carried out in the 32 IHC positive cases. There were 13 FISH-positive cases if the threshold was set as >15% of the 100 counted tumor cells having a split orange and green signal with more than one signal diameter. There were only 2 FISH-positive cases if the cutoff value was defined as >15% of the counted tumor cells having a split signal with more than two signal diameter widths. One of the FISH-positive cases had a separate NTRK3 FISH signal in 88% of the tumor cells, and its IHC result was strong nuclear staining in all the tumor cells. After evaluation of the morphology, it was re-diagnosed as secretory breast carcinoma, and the NGS result confirmed that it had a NTRK3-ETV6 fusion gene. The other FISH-positive cases were all negative for NTRK gene fusion in the NGS or RT-PCR examination. The NTRK gene fusion rate was low in our TNBC cohort. NTRK gene fusion may be a rare event in TNBC. The high false-positive rate of NTRK gene fusion detected by IHC questions its role as a prescreening method in TNBC. More data may be needed to determine a suitable threshold for NTRK FISH in TNBC in the future. More studies are needed to confirm whether RTK-targeted therapies are appropriate treatments for TNBC patients.


2021 ◽  
Vol 8 (27) ◽  
pp. 2439-2443
Author(s):  
Reshma Gopalakrishnan ◽  
Freena Rose ◽  
Jisha Kalathil Thodiyil ◽  
Lovely Jose

BACKGROUND Breast cancer is the most common malignancy in females. Triple negative breast carcinomas (TNBC), one of the molecular subtypes of breast carcinoma, are not sensitive to hormonal therapy and are reported to have aggressive behaviour. The present study was done to evaluate the expression of Ki67 in triple negative breast cancer using immunohistochemistry (IHC) and correlate the Ki67 expression with other clinicopathological variables. METHODS Based on the IHC status (ER, PR, HER neu), 50 triple negative breast carcinoma cases were selected from January 2019 to June 2020 for a cross-sectional study in Department of Pathology, Government medical college Thrissur. Ki67 immunohistochemical staining was done on the tissue sections and the Ki67 score was correlated with clinicopathological variables. RESULTS Of the 50 cases, majority (74 % cases) had high Ki67 expression (score of more than 50 %). High Ki67 score was strongly associated with presence of lymphovascular emboli (LVE) (P value < 0.05). Even though most of the patients were above 50 years (72 %), no significant correlation was seen between age and Ki67 score. The association with tumour size, histopathological type, tumour grade and lymph node status were not statistically significant. CONCLUSIONS Ki67 expression was high in triple negative breast cancer with mean score of 62 %. High Ki67 score correlated with presence of LVE. High Ki67 would predict increased proliferation of breast cancer cells and could be considered as a prognostic marker. KEYWORDS TNBC- Triple Negative Breast Cancer, Ki 67 Score, Clinicopathological Variables


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