Abstract 1928: Study of copy number amplification and chemo-response in triple negative breast cancer

Summary Background: Triple negative breast cancer (TNBC) is characterized by aggressive clinical course and is unresponsive to anti-HER2 and endocrine therapy. TNBC is difficult to treat and is often lethal. Given the need to find new targets for therapy we explored clinicopathological significance of copy number gain of FGFR1 and c-MYC. Our aim was to determine the impact of FGFR1 and c-MYC copy number gain on clinical course and outcome of TNBC. Methods: FGFR1 and c-MYC gene copy number alterations were evaluated in 78 archive TNBC samples using TaqMan based quantitative real time PCR assays. Results: 50% of samples had increased c-MYC copy number. c-MYC copy number gain was associated with TNBC in contrast to ER positive cancers. Our results showed significant correlation between c-MYC copy number gain and high grade of TNBCs. This suggests that c-MYC copy number could be an useful prognostic marker for TNBC patients. c-MYC copy number gain was associated with high pTNM stage as well as lobular and medullary tumor subtypes. 43% of samples had increased FGFR1 copy number. No correlations between FGFR1 copy number gain and clinicopathological variables were observed. Conclusions: We identified c-MYC copy number gain as a prognostic marker for TNBC. Our results indicate that c- MYC may contribute to TNBC progression. We observed no significant association between c-MYC and/or FGFR1 copy number status and patient survival.

Download Full-text

1q21.3 amplification modulates therapy sensitivity in Triple Negative Breast Cancer

10.1101/2020.04.29.066993 ◽

2020 ◽

Author(s):

Ramakanth Chirravuri-Venkata ◽

Dario Ghersi ◽

Apar K. Ganti ◽

Imayavaramban Lakshmanan ◽

Sanjib Chaudary ◽

...

Keyword(s):

Breast Cancer ◽

Risk Stratification ◽

Genetic Marker ◽

Triple Negative Breast Cancer ◽

Copy Number ◽

Triple Negative ◽

Copy Number Alterations ◽

Copy Number Status ◽

Cytotoxic Therapies

AbstractThe contrast in therapy sensitivity and response across triple negative breast cancer (TNBC) patients suggest underlying genotypic heterogeneity. Using publicly available data, we found significant associations between DNA-level copy number alterations of 1q21.3 locus and therapy sensitivity. We show that in spite of their aggressive nature, 1q21.3 amplified tumors are more responsive to commonly used cytotoxic therapies, highlighting the relevance of 1q21.3 copy number status as a genetic marker for risk stratification, therapy selection and response.

Download Full-text

Integrated copy number and miRNA expression analysis in triple negative breast cancer of Latin American patients

Oncotarget ◽

10.18632/oncotarget.27250 ◽

2019 ◽

Vol 10 (58) ◽

pp. 6184-6203 ◽

Cited By ~ 4

Author(s):

Bruna M. Sugita ◽

Silma R. Pereira ◽

Rodrigo C. de Almeida ◽

Mandeep Gill ◽

Akanksha Mahajan ◽

...

Keyword(s):

Breast Cancer ◽

Latin American ◽

Expression Analysis ◽

Triple Negative Breast Cancer ◽

Mirna Expression ◽

Copy Number ◽

Triple Negative

Download Full-text

59P Primary tumour and circulating tumour cell (CTC) copy number alterations (CNAs) in triple negative breast cancer (TNBC) patients (pts) treated with neoadjuvant chemotherapy (NAC)

Annals of Oncology ◽

10.1016/j.annonc.2020.03.193 ◽

2020 ◽

Vol 31 ◽

pp. S35-S36

Author(s):

S. Di Cosimo ◽

M. Silvestri ◽

M. Dugo ◽

M. Vismara ◽

C. Reduzzi ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Triple Negative Breast Cancer ◽

Tumour Cell ◽

Copy Number ◽

Triple Negative ◽

Primary Tumour ◽

Copy Number Alterations ◽

Circulating Tumour Cell

Download Full-text

Next generation sequencing reveals CCNE1 amplification as an independent prognostic factor for triple negative breast cancer (TNBC) patients.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.558 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 558-558

Author(s):

Xin Huang ◽

Huanwen M. Wu ◽

Changbin Zhu ◽

Di Shao ◽

Dan Guo ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Copy Number ◽

Triple Negative ◽

Genetic Data ◽

Genetic Alterations ◽

Clinicopathological Parameters ◽

Genomic Profiling ◽

Cyclin E1 ◽

Comprehensive Genomic Profiling

558 Background: Triple negative breast cancer (TNBC) has the worst prognosis among breast cancer due to the heterogeneity as well as lack of better therapeutic approach. It remains controversial whether BRCA status is the predictor of survival in TNBC. Besides, both germline and somatic mutation may contribute to the prognosis. This study is to explore the potential predictors and therapeutic targets based on genetic data and clinicopathological parameters. Methods: Seventy-five TNBC patients were enrolled with approximately 2:1 based on BRCA status. Genetic data was analysed by comprehensive genomic profiling 508 key cancer related genes. DAVID was applied to perform pathway enrichment analysis of significant enriched genetic alterations. Cox regression model was applied to evaluate disease-free survival (DFS) and overall survival (OS). Immuno-chemistry (IHC) was used to validate clinically meaningful genetic alteration. Results: In this study, 27 germline mutations were detected, including 26 homologous recombination repair (HRR) pathway gene mutations and 1 mismatch repair gene mutation among them 16 BRCA1 mutations and 5 BRCA2 mutations were found. Germline HRR including BRCA1/2 mutation marginally affected DFS ( p = 0.0624 and 0.15, respectively). We found 480 somatic genetic alterations including 110 copy number variations (CNV). The median value of TMB was determined to be 4.1 Muts/Mb which divided 74 TNBC patients into TMB-low (TMB-l) and TMB-high (TMB-h) group. TMB-l group had inferior DFS to TMB-h ( p = 0.0457). CCNE1 (with 5% frequency) copy number gain was specifically enriched in TMB-l group but mutually exclusive with BRCA1/2 mutation. TNBC with CCNE1 gain displayed worse DFS ( p< 0.0001). Cox multivariate regression analysis indicated CCNE1 gain was an independent risk factors for DFS [HR = 13.48 (95% CI 2.62-69.23), p= 0.002)]. Pathway analysis indicated CCNE1 harmed prognosis through regulation of transcription in G1/S phase. Expression of cyclin E1 was validated by IHC, which would be presented later. Conclusions: Comprehensive genomic profiling disclosed various potential prognostic markers for TNBC by integrating clinical characters. Especially, amplified CCNE1 may be a potential prognostic marker and therapeutic target. [Table: see text]

Download Full-text