Dataset Information

Genetic and clinical landscape of ER + /PR- breast cancer in China.

ABSTRACT:

Background

Estrogen receptor-positive and progesterone receptor-negative (ER + /PR-) breast cancer comprise a special type. More than 10% breast cancer patients belonged to ER + /PR-.

Methods

In order to better understand this patient population, we utilized a unique dataset from China, examining the clinicopathological features and genomic profiles of ER + /PR- breast cancers. Our study involved three cohorts: Cohort 1 included 2120 unselected ER-positive female patients with re-evaluated clinicopathological and survival data; Cohort 2 comprised 442 ER-positive females who underwent genetic testing; and Cohort 3 consisted of 77 ER-positive/HER2-negative females tested with MammaPrint and BluePrint.

Results

Patients were stratified into four categories based on the PR/ER ratio. Clinically, ER + /PR- tumors (PR/ER ratio = 0) showed the lowest proportion of T1 tumors (10.88%) and highest proportion of HER2-positive tumors (28.36%) than did other ER + /PR + tumors groups. The ER + /PR- group contained a higher number of underweight patients (20.20%). Independently of HER2 status, ER + /PR- patients demonstrated the poorest prognosis. Genomically, the most prevalent mutations were PIK3CA (50%) in ER + /PR + tumors and TP53 (65%) in ER + /PR- tumors. ER + /PR- tumors presented more frequent mutations in TP53, ERBB2, CDK12, SPEN, and NEB, with mutation rates of 65%, 42%, 27%, 13%, and 10%, respectively. Additionally, the Tumor Mutational Burden (TMB) was higher in the ER + /PR- group compared to the ER + /PR + group. The MammaPrint score for the ER + /PR-/HER2- group was significantly lower than that of other groups. In the BluePrint analysis, only four patients were classified as Basal-Type, all of whom were ER + /PR-/HER2-.

Conclusions

In this study, we identified the clinical and genetic characteristics of ER + /PR- breast cancer patients in China. Distinct PR statuses indicated different biological processes of ER + breast cancer and survival outcomes. Future treatment strategies may need to be tailored for ER + /PR- patients.

SUBMITTER: Dai D

PROVIDER: S-EPMC10696783 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Publications

Genetic and clinical landscape of ER + /PR- breast cancer in China.

Dai Danian D Wu Hongmei H Zhuang Hongkai H Chen Rong R Long Cheng C Chen Bo B

BMC cancer 20231204 1

<h4>Background</h4>Estrogen receptor-positive and progesterone receptor-negative (ER + /PR-) breast cancer comprise a special type. More than 10% breast cancer patients belonged to ER + /PR-.<h4>Methods</h4>In order to better understand this patient population, we utilized a unique dataset from China, examining the clinicopathological features and genomic profiles of ER + /PR- breast cancers. Our study involved three cohorts: Cohort 1 included 2120 unselected ER-positive female patients with re- ...[more]

PMID: 38049758

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Project description:BackgroundThe clinically high comorbidity between polycystic ovary syndrome (PCOS) and breast cancer (BC) has been extensively reported. However, limited knowledge exists regarding their shared genetic basis and underlying mechanisms.MethodLeveraging summary statistics from the largest genome-wide association studies (GWASs) to date, we conducted a comprehensive genome-wide cross-trait analysis of PCOS and BC. A variety of genetic statistical methods were employed to uncover potential shared genetic causes.ResultsOur analysis revealed genetic overlap between the three trait pairs. After partitioning the genome into 2,495 independent regions, we identified two loci, chr8: 75,011,700-76,295,483 and chr17: 6,305,079-7,264,458, with significant localized genetic correlations. Pleiotropic analysis under a composite null hypothesis identified 1,183 significant pleiotropic single nucleotide polymorphisms (SNPs) across three trait pairs. FUMA mapped 26 pleiotropic loci, with regions 16q12.2 and 6q25.1 duplicated across all three trait pairs, while COLOC detected three loci with colocalization evidence. Gene-based analysis identified 23 unique candidate pleiotropic genes, including the FTO shared by all trait pairs, as well as SER1, RALB, and others in two trait pairs. Pathway enrichment analysis further highlighted key biological pathways, primarily involving the significant biological pathways were the metabolism of regulation of autophagy, regulation of cellular catabolic process, and positive regulation of catabolic process. Latent Heritable Confounder Mendelian randomization (LHC-MR) supported a positive causal relationship between PCOS and both BCALL and ERPBC but not with ERNBC.ConclusionIn conclusion, our genome-wide cross-trait analysis identified a shared genetic basis between PCOS and BC, specific identical genetic mechanisms and causality between PCOS and various BC subtypes, which could better explains the genetics of the co-morbidity of PCOS and ERPBC rather than PCOS and ERNBC. These findings provide new insights into the biological mechanisms underlying the co-morbidity of these two complex diseases, which have important implications for clinical disease intervention, treatment, and improved prognosis.

Project description:AimsThe available research on the association between estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), ER-/PR+ status, and the occurrence of lung cancer subsequent to breast cancer in patients (referred to as BC-LuC) had been limited. Consequently, there is a need to examine whether ER, PR, HER2, and ER-/PR+ have independent correlations with the risk and outcomes of BC-LuC, while appropriately adjusting for other potential covariates.MethodsThe present study employed a cohort design and utilized data from the Surveillance, Epidemiology, and End Results (SEER) program spanning from 2010 to 2015. The study population consisted of 683,336 individuals who were diagnosed with breast cancer (referred to as BC). Various covariates were assessed at baseline, including age, sex, race, marital status, CS tumor size, laterality, radiation, chemotherapy, months from diagnosis to treatment, breast subtype, AJCC 7th edition (2010-2015), and combined summary stage (2004+). The primary objective of this study was to investigate the association between ER, PR, HER2, ER-/PR+ status, and the risk of developing BC-LuC. Logistic regression analysis was employed to assess this association. Furthermore, multivariable Cox regression analyses were conducted to calculate adjusted hazard ratios (HRs) along with their respective 95% confidence intervals (CIs). Kaplan-Meier plots and log-rank tests were utilized to estimate the outcomes, specifically overall survival (OS), disease-specific survival (DSS), and metastasis.ResultsThe average age of 198,972 selected participants was 59.8 ± 13.1 years, and about 99.3% of them were female. Result of fully adjusted binary logistic regression showed PR+ and HER2+ were positively associated with lower risk BC-LuC after adjusting confounders (ORs = 0.84, 95% CI: 0.73-0.96, p = 0.011 and ORs = 0.83, 95% CI: 0.72-0.96, p = 0.012, respectively). ER+ and ER-/PR+ were detected no significant relationship with BC-LuC (ORs = 1.03, 95% CI: 0.87-1.22, p = 0.718 and ORs = 1.02, 95% CI: 0.61-1.72, p = 0.936, respectively). In subgroups analyses, the results remain stable. Multivariable Cox regression showed that BC-LuC patients with ER and PR were significantly associated with OS and DSS. However, ER, PR, HER2, and ER-/PR+ were significantly associated with OS and DSS in breast cancer patients. The relationship between ER, PR, HER2, and ER-/PR+ and metastasis in breast cancer patients was different.ConclusionThe results of this study indicated a potential correlation between PR- and HER2- status and a risk of developing BC-LuC. Furthermore, it appears that the prognosis of BC-LuC may be influenced by the presence of ER+ and PR+. Therefore, additional research is warranted to fully investigate and validate this association.

Dataset Information

Genetic and clinical landscape of ER + /PR- breast cancer in China.

Background

Methods

Results

Conclusions

Publications

Genetic and clinical landscape of ER + /PR- breast cancer in China.

Similar Datasets

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