Dataset Information

Molecular subtypes of triple-negative breast cancer in women of different race and ethnicity.

ABSTRACT: Molecular subtypes of triple negative breast cancer (TNBC) are associated with variation in survival and may assist in treatment selection. However, the association of patient race or ethnicity with subtypes of TNBC and clinical outcome has not been addressed. Using nCounter Gene Expression Codesets, we classified TNBCs into subtypes: basal-like immune-activated (BLIA), basal-like immunosuppressed (BLIS), luminal androgen receptor (LAR), and mesenchymal (MES) in 48 Hispanic, 12 African-American, 21 Asian, and 34 White patients. Mean age at diagnosis was significantly associated with subtype, with the youngest mean age (50 years) in MES and the oldest mean age (64 years) in LAR (p < 0.0005). Subtype was significantly associated with tumor grade (p = 0.0012) and positive lymph nodes (p = 0.021), with a marginally significant association of tumor stage (p = 0.076). In multivariate Cox-proportional hazards modeling, BLIS was associated with worst survival and LAR with best survival. Hispanics had a significantly higher proportion of BLIS (53%, p = 0.03), whereas Asians had a lower proportion of BLIS (19%, p = 0.05) and a higher proportion of LAR (38%, p = 0.06) compared to the average proportion across all groups. These differences in proportions of subtype across racial and ethnic groups may explain differences in their outcomes. Determining subtypes of TNBC facilitates understanding of the heterogeneity of the TNBCs and provides a foundation for developing subtype-specific therapies and better predictors of TNBC prognosis for all races and ethnicities.

SUBMITTER: Ding YC

PROVIDER: S-EPMC6349443 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Molecular subtypes of triple-negative breast cancer in women of different race and ethnicity.

Ding Yuan Chun YC Steele Linda L Warden Charles C Wilczynski Sharon S Mortimer Joanne J Yuan Yuan Y Neuhausen Susan L SL

Oncotarget 20190104 2

Molecular subtypes of triple negative breast cancer (TNBC) are associated with variation in survival and may assist in treatment selection. However, the association of patient race or ethnicity with subtypes of TNBC and clinical outcome has not been addressed. Using nCounter Gene Expression Codesets, we classified TNBCs into subtypes: basal-like immune-activated (BLIA), basal-like immunosuppressed (BLIS), luminal androgen receptor (LAR), and mesenchymal (MES) in 48 Hispanic, 12 African-American, ...[more]

PMID: 30719214

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Project description:Triple-negative breast cancer (TNBC) is a heterogeneous disease that can be classified into distinct molecular subtypes by gene expression profiling. Considered a difficult-to-treat cancer, a fraction of TNBC patients benefit significantly from neoadjuvant chemotherapy and have far better overall survival. Outside of BRCA1/2 mutation status, biomarkers do not exist to identify patients most likely to respond to current chemotherapy; and, to date, no FDA-approved targeted therapies are available for TNBC patients. Previously, we developed an approach to identify six molecular subtypes TNBC (TNBCtype), with each subtype displaying unique ontologies and differential response to standard-of-care chemotherapy. Given the complexity of the varying histological landscape of tumor specimens, we used histopathological quantification and laser-capture microdissection to determine that transcripts in the previously described immunomodulatory (IM) and mesenchymal stem-like (MSL) subtypes were contributed from infiltrating lymphocytes and tumor-associated stromal cells, respectively. Therefore, we refined TNBC molecular subtypes from six (TNBCtype) into four (TNBCtype-4) tumor-specific subtypes (BL1, BL2, M and LAR) and demonstrate differences in diagnosis age, grade, local and distant disease progression and histopathology. Using five publicly available, neoadjuvant chemotherapy breast cancer gene expression datasets, we retrospectively evaluated chemotherapy response of over 300 TNBC patients from pretreatment biopsies subtyped using either the intrinsic (PAM50) or TNBCtype approaches. Combined analysis of TNBC patients demonstrated that TNBC subtypes significantly differ in response to similar neoadjuvant chemotherapy with 41% of BL1 patients achieving a pathological complete response compared to 18% for BL2 and 29% for LAR with 95% confidence intervals (CIs; [33, 51], [9, 28], [17, 41], respectively). Collectively, we provide pre-clinical data that could inform clinical trials designed to test the hypothesis that improved outcomes can be achieved for TNBC patients, if selection and combination of existing chemotherapies is directed by knowledge of molecular TNBC subtypes.

Project description:ImportanceBreast cancer incidence trends by age and race/ethnicity have been documented; it is less clear whether incidence trends of breast cancer molecular subtypes, which differ in risk factors and prognosis, also vary by age and race/ethnicity.ObjectiveTo estimate annual percentage changes and trends in breast cancer molecular subtype-specific incidence rates by age at diagnosis and race/ethnicity in the US.Design, setting, and participantsThis population-based cross-sectional study included data from 18 cancer registries in the Surveillance, Epidemiology and End Results database, capturing 27.8% of the US population. Hispanic and non-Hispanic White, Black, and Asian/Pacific Islander women aged 25 to 84 years who were diagnosed with invasive breast cancer from 2010 to 2016 were included. Data were analyzed from September 2019 to February 2020.ExposuresAge and racial/ethnic groups.Main outcomes and measuresAnnual percentage change (APC) and 95% CIs for age-standardized breast cancer incidence rates stratified by 15-year age groups at diagnosis and race/ethnicity.ResultsOf 320 124 women diagnosed with breast cancer from 2010 to 2016, 232 558 (72.6%) had luminal A, 35 869 (11.2%) had luminal B, 15 472 (4.8%) had ERBB2-enriched, and 36 225 (11.3%) had triple-negative breast cancer subtypes. Luminal A breast cancer incidence rates increased in non-Hispanic White (APC from 2010-2014, 2.3%; 95% CI, 0.3% to 4.2%) and non-Hispanic Asian/Pacific Islander (APC from 2010-2016, 2.5%; 95% CI, 0.6% to 4.5%) women aged 40 to 54 years, and in non-Hispanic Black women aged 55 to 69 years women (APC from 2010-2012, 4.9%; 95% CI, 4.0% to 5.7%). Luminal B breast cancer incidence rates increased in all age groups for non-Hispanic White women (age 25-39 years: APC, 4.3%; 95% CI, 1.5% to 7.%2; age 40-54 years: APC, 3.5%; 95% CI, 1.4% to 5.6%; age 55-69 years: APC, 3.3%; 95% CI, 1.6% to 5.0%; age 70-84 years: APC, 3.9%; 95% CI, 1.9% to 6.0%) and Hispanic women (age 25-39 years: APC, 8.4%; 95% CI, 5.8% to 11.2%; age 40-54 years: APC, 6.1%; 95% CI, 4.2% to 8.0%; age 55-69 years: APC, 5.1%; 95% CI, 1.5% to 8.8%; age 70-84 years: APC, 7.1%; 95% CI, 4.6% to 9.6%) and in non-Hispanic Asian/Pacific Islander women aged 55 to 69 years (APC, 6.1%; 95% CI, 3.2% to 9.0%). ERBB2-enriched breast cancer incidence rates increased in non-Hispanic White women aged 25 to 39 years (APC, 4.7%; 95% CI, 1.5% to 8.0%). Triple-negative breast cancer incidence rates decreased in non-Hispanic White women aged 40 to 54 years (APC, -2.3%; 95% CI, -3.8% to -0.7%) and 55 to 69 years (APC, -3.6%; 95% CI, -5.1% to -2.1%) and in non-Hispanic Black women aged 55 to 69 years (APC, -1.4%; 95% CI, -2.2% to -0.7%).Conclusions and relevanceThe findings of this cross-sectional study suggest that between 2010 and 2016, luminal A and luminal B breast cancer incidence rates increased for many racial/ethnic and age groups, with the largest increases observed for luminal B breast cancer. ERBB2-enriched breast cancer incidence rates increased for young non-Hispanic White women, while triple-negative breast cancer incidence rates decreased for midlife non-Hispanic White and non-Hispanic Black women. These trends may suggest changes in breast cancer risk factor profiles across age and racial/ethnic groups.

Project description:Necroptosis, a kind of programmed necrotic cell apoptosis, is the gatekeeper for the host to defend against the invasion of pathogens. It helps to regulate different biological processes regarding human cancer. Nevertheless, studies that determine the impact of death on triple-negative breast cancer (TNBC) are scarce. Therefore, this paper has comprehensively examined the expression as well as clinical significance of necroptosis in TNBC. ConsensusClusterPlus was used to establish a stable molecular classification that used the expression regarding the necroptosis-linked genes. The clinical and immune characteristics of different subclasses were evaluated. Then, the weighted gene coexpression network analysis (WGCNA) assisted in determining key modules, and we selected the genes exhibiting obvious association with necroptosis prognosis through the relationship with prognosis. The univariate Cox regression analysis together with least absolute shrinkage and selection operator (LASSO) techniques served for the construction of the necroptosis-related prognostic risk score (NPRS) model, and the pathway characteristics of NPRS model grouping were further studied. Finally, the NPRS, taking into account the clinicopathological features, used the decision tree model for enhancing the prognostic model as well as the survival prediction. First, two stable molecular subtypes with different prognosis and immune characteristics were identified using necroptosis marker genes. Then, the key modules were identified, and 10 genes significantly related to the prognosis of necroptosis were selected. Then, the clinical prognostic model of NPRS was developed considering the prognosis-linked necroptosis genes. Finally, the NPRS model, taking into account the clinicopathological features, adopted the decision tree model for enhancing the prognostic model as well as the survival prediction. Herein, two new molecular subgroups considering necroptosis-linked genes are proposed, and an NPRS model composed of 10 genes is developed, which maybe assist in the personalized treatment and clinical treatment guidance of TNBC patients.

Dataset Information

Molecular subtypes of triple-negative breast cancer in women of different race and ethnicity.

Publications

Molecular subtypes of triple-negative breast cancer in women of different race and ethnicity.

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