The TRIM37 variant rs57141087 contributes to triple-negative breast cancer outcomes in Black women
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ABSTRACT:
SUBMITTER: Dr. Sanchita Bhatnagar
PROVIDER: S-SCDT-10_1038-S44319-024-00331-2 | biostudies-other |
REPOSITORIES: biostudies-other
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Project description:Triple-negative breast cancer (TNBC) refers to one aggressive histological subtype of breast cancer with high heterogeneity and poor prognosis after standard therapy. Lack of clearly established molecular mechanism driving TNBC progression makes personalized therapy more difficult. Thus, identification of genetic variants associated with TNBC prognosis will show clinic significance for individualized treatments. Our study is aimed to evaluate the prognostic value of the genome wide association study (GWAS)-identified CHST9 rs1436904 and AQP4 rs527616 genetic variants in our established early-stage TNBC sample database. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). CHST9 rs1436904G allele was significantly associated with decreased disease-free survival time (DFS) (8.5 months shorter in GG genotype carriers compared to TT genotype carriers, HR = 1.70, 95% CI = 1.03-2.81, P = 0.038). Stratified analyses showed an increased risk of cancer progression in CHST9 rs1436904G allele carriers harboring larger tumor (tumor size > 2 cm), without lymph-node metastasis, being premenopausal at diagnosis or with vascular invasion (P = 0.032, 0.017, 0.008 or 0.003). Our findings demonstrate that the GWAS-identified 18q11.2 CHST9 rs1436904 polymorphism significantly contributes to prognosis of early-stage TNBC, suggesting its clinical potential in the screening of high-risk TNBC patients for recurrence and the possibility of patient-tailored therapeutic decisions.
| S-EPMC5603563 | biostudies-literature
Project description:PurposeUnderstanding the contribution of tumor genome biology to racial disparities of triple-negative breast cancer (TNBC) is important for narrowing the cancer mortality gap between Black and White women.MethodsWe evaluated tumor somatic mutations using targeted sequencing of a customized panel of 151 genes and 15 copy number variations (CNVs) within a population of 133 TNBC patients, including 71 Black and 62 White women.ResultsThe overall mutational burden between Black and White women with TNBC was not significantly different, with a median of 5 somatic changes per patient (point mutations and CNVs combined) for the customized panel (range 1-31 for Blacks vs. 1-26 for Whites; p = 0.76). Of the 151 genes examined, none were mutated at a significantly higher frequency in Black than in White cases, whereas two genes were mutated at a higher frequency in White cases-PIK3CA and NCOR1. No significant difference in the frequency of CNVs was observed between Black and White women with TNBC in our study population.ConclusionOf gene mutations and CNVs in TNBC tumors from Black and White women, only PIK3CA and NCOR1 had significantly different, although slight, frequencies by race. These results indicate that overall differences observed in the mutation spectra between Black and White women with breast cancer are likely due to the differential distributions of breast cancer subtypes by race.
| S-EPMC7313393 | biostudies-literature
Project description:PurposeTriple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, characterized by substantial risks of early disease recurrence and mortality. We constructed and validated clinical calculators for predicting recurrence-free survival (RFS) and overall survival (OS) for TNBC.MethodsData from 605 women with centrally confirmed TNBC who underwent primary breast cancer surgery at Mayo Clinic during 1985-2012 were used to train risk models. Variables included age, menopausal status, tumor size, nodal status, Nottingham grade, surgery type, adjuvant radiation therapy, adjuvant chemotherapy, Ki67, stromal tumor-infiltrating lymphocytes (sTIL) score, and neutrophil-to-lymphocyte ratio (NLR). Final models were internally validated for calibration and discrimination using ten-fold cross-validation and compared with their base-model counterparts which include only tumor size and nodal status. Independent external validation was performed using data from 478 patients diagnosed with stage II/III invasive TNBC during 1986-1992 in the British Columbia Breast Cancer Outcomes Unit database.ResultsFinal RFS and OS models were well calibrated and associated with C-indices of 0.72 and 0.73, as compared with 0.64 and 0.62 of the base models (p < 0.001). In external validation, the discriminant ability of the final models was comparable to the base models (C-index: 0.59-0.61). The RFS model demonstrated greater accuracy than the base model both overall and within patient subgroups, but the advantages of the OS model were less profound.ConclusionsThis TNBC clinical calculator can be used to predict patient outcomes and may aid physician's communication with TNBC patients regarding their long-term disease outlook and planning treatment strategies.
| S-EPMC7925385 | biostudies-literature
Project description:Patients with triple-negative breast cancer (TNBC) lack molecular targets and have an unfavorable outcome. CD155 is overexpressed in human cancers, but whether it plays a role in TNBC is unexplored. Here we found that CD155 was enriched in both TNBC cell lines and tumor tissues. High CD155 expression was related to poor prognosis of breast cancer patients. CD155 was associated with a mesenchymal phenotype. CD155 knockdown induced a mesenchymal-epithelial transition in TNBC cells, and suppressed TNBC cell migration, invasion and metastasis in vitro and in vivo. Mechanistically, CD155 cross-talked with oncogenic IL-6/Stat3 and TGF-?/Smad3 pathways. Moreover, CD155 knockdown inhibited TNBC cell growth and survival. Taken together, these data indicate that CD155 contributes to the aggressive behavior of TNBC; targeting CD155 may be beneficial to these patients.
| S-EPMC7004517 | biostudies-literature
Project description:Purpose: We sought to investigate if the use of HMG Co-A reductase inhibitors (statins) has an impact on outcomes among patients with triple negative breast cancer (TNBC). Methods: We reviewed the cases of women with invasive, non-metastatic TNBC, diagnosed 1997-2012. Clinical outcomes were compared based on statin use (defined as ever use during treatment vs. never use). We identified a subset of women for whom a 5-value lipid panel (5VLP) was available, including total cholesterol, low density lipoprotein, high density lipoprotein, very low density lipoprotein, and triglycerides. The Kaplan-Meier method was used to estimate median overall survival (OS), distant metastases-free survival (DMFS), and local-regional recurrence-free survival (LRRFS). A Cox proportional hazards regression model was used to test the statistical significance of prognostic factors. Results: 869 women were identified who met inclusion criteria, with a median follow-up time of 75.1 months (range 2.4-228.9 months). 293 (33.7%) patients used statins and 368 (42.3%) had a 5VLP. OS, DMFS, and LRRFS were not significant based on statin use or type. Controlling for the 5VLP values, on multivariable analysis, statin use was significantly associated with OS (HR 0.10, 95% CI 0.01-0.76), but not with DMFS (HR 0.14, 95% CI 0.01-1.40) nor LRRFS (HR 0.10 95% CI 0.00-3.51). Conclusions: Statin use among patients with TNBC is not associated with improved OS, although it may have a benefit for a subset of patients. Prospective assessment would be valuable to better assess the potential complex correlation between clinical outcome, lipid levels, and statin use.
| S-EPMC5559964 | biostudies-other
Project description:Triple-negative breast cancer (TNBC) represents 15%-20% of all breast cancer types. It is more common among African American (AA) and Hispanic-Latina (HL) women. The biology of TNBC in HL women has been poorly characterized, but some data suggest that the molecular drivers of breast cancer might differ. There are no clinical tools to aid medical oncologists with decisions regarding appropriate individualized therapy, and no way to predict long-term outcomes. The aim of this study was to characterize individual patient gene mutation profiles and to identify the relationship with clinical outcomes. We collected formalin-fixed paraffin-embedded tumors (FFPE) from women with TNBC. We analyzed the gene mutation profiles of the collected tumors and compared the results with individual patient's clinical histories and outcomes. Of 25 patients with TNBC, 24 (96%) identified as HL. Twenty-one (84%) had stage III-IV disease. The most commonly mutated genes were TP53, NOTCH1, NOTCH2, NOTCH3, AKT, MEP3K, PIK3CA, and EGFR. Compared with other international cancer databases, our study demonstrated statistically significant higher frequencies of these genes among HL women. Additionally, a worse clinical course was observed among patients whose tumors had mutations in NOTCH genes and PIK3CA. This study is the first to identify the most common genetic alterations among HL women with TNBC. Our data strongly support the notion that molecular drivers of breast cancer could differ in HL women compared with other ethnic backgrounds. Therefore, a deeper understanding of the biological mechanisms behind NOTCH gene and PIK3CA mutations may lead to a new treatment approach.
| S-EPMC7473586 | biostudies-literature
Project description:IntroductionWe investigated clinical and pathologic features of breast cancers (BC) in an unselected series of patients diagnosed in a tertiary care hospital serving a diverse population. We focused on triple-negative (Tneg) tumours (oestrogen receptor (ER), progesterone receptor (PR) and HER2 negative), which are associated with poor prognosis.MethodsWe identified female patients with invasive BC diagnosed between 1998 and 2006, with data available on tumor grade, stage, ER, PR and HER2 status, and patient age, body mass index (BMI) and self-identified racial/ethnic group. We determined associations between patient and tumour characteristics using contingency tables and multivariate logistic regression.Results415 cases were identified. Patients were racially and ethnically diverse (born in 44 countries, 36% white, 43% black, 10% Hispanic and 11% other). 47% were obese (BMI > 30 kg/m2). 72% of tumours were ER+ and/or PR+, 20% were Tneg and 13% were HER2+. The odds of having a Tneg tumour were 3-fold higher (95% CI 1.6, 5.5; p = 0.0001) in black compared with white women. Tneg tumours were equally common in black women diagnosed before and after age 50 (31% vs 29%; p = NS), and who were obese and non-obese (29% vs 31%; p = NS). Considering all patients, as BMI increased, the proportion of Tneg tumours decreased (p = 0.08).ConclusionsBlack women of diverse background have 3-fold more Tneg tumours than non-black women, regardless of age and BMI. Other factors must determine tumour subtype. The higher prevalence of Tneg tumours in black women in all age and weight categories likely contributes to black women's unfavorable breast cancer prognosis.
| S-EPMC2688946 | biostudies-literature
Project description:Perou's molecular classification defines tumors that neither express hormone receptors nor overexpress HER2 as triple-negative (TN) tumors. These tumors account for approximately 15% of breast cancers. The so-called basaloid tumors are not always synonymous with TN tumors; they differ in the fact that they express different molecular markers, have a higher histologic grade, and have a worse prognosis. Clinically they occur in younger women as interval cancer, and the risk of recurrence is higher within the first 3 years. Distant recurrences in the brain and visceral metastases are more common than in hormone receptor-positive tumors. Therapeutically, despite being highly chemosensitive, their progression-free time is generally short. In terms of chemotherapeutic treatment, anthracyclines and taxanes are useful drugs, and high response rates have been described for the combination of ixabepilone-capecitabine and platinums. The combination with antiangiogenic drugs has also proven useful. A group of new drugs, poly-(ADP-ribose)-polymerase inhibitors, showed favorable results in TN tumors with BRCA mutation. There are currently several ongoing studies with new drugs including epidermal growth factor receptor inhibitors, c-kit inhibitors, Raf/Mek/Map kinase inhibitors and mTOR inhibitors.
| S-EPMC2972557 | biostudies-literature
Project description:Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype that disproportionately affects BRCA1 mutation carriers and young women of African origin. There is evidence that African-American women with TNBC have worse clinical outcomes than women of European descent. However, it is unclear whether survival differences persist after adjusting for disparities in access to health-care treatment, co-morbid disease and income. It remains controversial whether TNBC in African-American women is a molecularly distinct disease or whether African-American women have a higher incidence of aggressive biology driven by disparities: there is evidence in support of both. Understanding the relative contributions of biology and disparities is essential for improving the poor survival rate of African-American women with TNBC.
| S-EPMC5470637 | biostudies-literature
Project description:To describe survival according to prognostic factors of women with breast cancer in French overseas territory (Martinique) during 2008-2017. We performed a Cox model for prognostic factors for OS in breast cancer patients. The cut-off date for the analysis was 13/10/2018. The main factors were demographic data, stage, hormone receptors (HR) status and HER2 status. Curves were compared with the log rank test to select candidate variables for the multivariate analysis. We included 1,708 patients; median age at diagnosis was 57 years. Triple negative breast cancer (TNBC) accounted for 20.9% (n = 332). Among the patients, 72.3% (n = 1015) had localised or local spread cancer. One-year OS was 95.2% and was 80.1% at 5 years. In TNBC, 1-year-survival was 90.4%, which fell to 70.1% at 5 years. Patients with metastatic disease at diagnosis had 1-year-survival of 74.5%, and 20.1% at 5 years. Multivariate analysis by Cox regression identified 4 factors significantly associated with an increased risk of death: metastatic disease at diagnosis (hazard ratio (HR) = 15, p<0.0001), TNBC (HR 2.84, p<0.0001), HR+/HER2- status (HR 2.05, p<0.0084) and age >75 years (HR 3.8, p<0.0001). This is the first study performed on breast cancer survival in Martinique. Our findings show that breast cancer has overall good prognosis in patients and also how prognosis factors are distributed in the population.
| S-EPMC9401158 | biostudies-literature