Gene expression data for 637 human primary breast tumors with recurrence, ER/PR/HER2 status, and overall survival
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE199633 | GEO | 2024/06/07
REPOSITORIES: GEO
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Project description:Gene expression data for 637 human primary breast tumors with recurrence, ER/PR/HER2 status, and overall survival
| PRJNA820880 | ENA
Project description:PurposeTo investigate the impact of chemotherapy relative dose intensity (RDI) on cause-specific and overall survival for stage I-III breast cancer: estrogen receptor or progesterone receptor positive, human epidermal-growth factor receptor negative (ER+/PR+ and HER2-) vs. triple-negative (TNBC) and to identify the optimal RDI cut-off points in these two patient populations.MethodsData were collected by the Louisiana Tumor Registry for two CDC-funded projects. Women diagnosed with stage I-III ER+/PR+, HER2- breast cancer, or TNBC in 2011 with complete information on RDI were included. Five RDI cut-off points (95, 90, 85, 80, and 75%) were evaluated on cause-specific and overall survival, adjusting for multiple demographic variables, tumor characteristics, comorbidity, use of granulocyte-growth factor/cytokines, chemotherapy delay, chemotherapy regimens, and use of hormone therapy. Cox proportional hazards models and Kaplan-Meier survival curves were estimated and adjusted by stabilized inverse probability treatment weighting (IPTW) of propensity score.ResultsOf 494 ER+/PR+, HER2- patients and 180 TNBC patients, RDI < 85% accounted for 30.4 and 27.8%, respectively. Among ER+/PR+, HER2- patients, 85% was the only cut-off point at which the low RDI was significantly associated with worse overall survival (HR = 1.93; 95% CI 1.09-3.40). Among TNBC patients, 75% was the cut-off point at which the high RDI was associated with better cause-specific (HR = 2.64; 95% CI 1.09, 6.38) and overall survival (HR = 2.39; 95% CI 1.04-5.51).ConclusionsHigher RDI of chemotherapy is associated with better survival for ER+/PR+, HER2- patients and TNBC patients. To optimize survival benefits, RDI should be maintained ≥ 85% in ER+/PR+, HER2- patients, and ≥ 75% in TNBC patients.
| S-EPMC6190707 | biostudies-literature
Project description:BackgroundGenetic alterations in cellular signaling networks are a hallmark of cancer, however, effective methods to discover them are lacking. A novel form of abnormality called acquired uniparental disomy (aUPD) was recently found to pinpoint the region of mutated genes in various cancers, thereby identifying the region for next-generation sequencing.Methods/principal findingsWe retrieved large genomic data sets from the Gene Expression Omnibus database to perform genome-wide analysis of aUPD in breast tumor samples and cell lines using approaches that can reliably detect aUPD. aUPD was identified in 52.29% of the tumor samples. The most frequent aUPD regions were located at chromosomes 2q, 3p, 5q, 9p, 9q, 10q, 11q, 13q, 14q and 17q. We evaluated the data for any correlation between the most frequent aUPD regions and HER2/neu, ER, and PR status, and found a statistically significant correlation between the recurrent regions of aUPD and triple negative (TN) breast cancers. aUPD at chromosome 17q (VEZF1, WNT3), 3p (SUMF1, GRM7), 9p (MTAP, NFIB) and 11q (CASP1, CASP4, CASP5) are predictors for TN. The frequency of aUPD was found to be significantly higher in TN breast cancer cases compared to HER2/neu-positive and/or ER or PR-positive cases. Furthermore, using previously published mutation data, we found TP53 homozygously mutated in cell lines having aUPD in that locus.Conclusions/significanceWe conclude that aUPD is a common and non-random molecular feature of breast cancer that is most prominent in triple negative cases. As aUPD regions are different among the main pathological subtypes, specific aUPD regions may aid the sub-classification of breast cancer. In addition, we provide statistical support using TP53 as an example that identifying aUPD regions can be an effective approach in finding aberrant genes. We thus conclude that a genome-wide scale analysis of aUPD regions for homozygous sequence alterations can provide valuable insights into breast tumorigenesis.
| S-EPMC2994899 | biostudies-literature
Project description:Because histologic types are subjective and difficult to reproduce between pathologists, tissue morphology often takes a back seat to molecular testing for the selection of breast cancer treatments. This work explores whether a deep-learning algorithm can learn objective histologic H&E features that predict the clinical subtypes of breast cancer, as assessed by immunostaining for estrogen, progesterone, and Her2 receptors (ER/PR/Her2). Translating deep learning to this and related problems in histopathology presents a challenge due to the lack of large, well-annotated data sets, which are typically required for the algorithms to learn statistically significant discriminatory patterns. To overcome this limitation, we introduce the concept of "tissue fingerprints," which leverages large, unannotated datasets in a label-free manner to learn H&E features that can distinguish one patient from another. The hypothesis is that training the algorithm to learn the morphological differences between patients will implicitly teach it about the biologic variation between them. Following this training internship, we used the features the network learned, which we call "fingerprints," to predict ER, PR, and Her2 status in two datasets. Despite the discovery dataset being relatively small by the standards of the machine learning community (n = 939), fingerprints enabled the determination of ER, PR, and Her2 status from whole slide H&E images with 0.89 AUC (ER), 0.81 AUC (PR), and 0.79 AUC (Her2) on a large, independent test set (n = 2531). Tissue fingerprints are concise but meaningful histopathologic image representations that capture biological information and may enable machine learning algorithms that go beyond the traditional ER/PR/Her2 clinical groupings by directly predicting theragnosis.
| S-EPMC7190637 | biostudies-literature
Project description:ER+/HER2- breast cancer is a common subtype of breast cancer. This study aimed to evaluate the prognostic value of ER-to-PR difference (EPD) in ER+/HER2- early breast cancer (EBC). A retrospective cohort study was conducted, including 3,340 ER+/HER2- EBC patients, divided into a training cohort of 2,873 patients and a validation cohort of 467 patients. The optimal EPD cutoff value for stratifying patients was determined using X-tile. Additionally, the prognostic value of EPD, when combined with other clinicopathological factors, was assessed using the Cox proportional hazards model and five traditional machine learning methods. The optimal cutoff value for EPD was determined as 10%, categorizing patients into EPD-low (ER-PR ≤ 10%) and EPD-high (ER-PR > 10%) expression groups. Patients with EPD-high tumors exhibited a poorer prognosis compared to those with EPD-low tumors. In the multivariate Cox model, EPD was identified as an independent prognostic factor for disease-free survival (DFS) (HR: 1.496, P = 0.004). Integrating EPD with clinicopathological parameters into a predictive model effectively predicts DFS in ER+/HER2- EBC patients. In the most effective CoxPH model, the area under the curve (AUC) values for predicting 3-year, 5-year, and 7-year DFS were 0.718, 0.702, and 0.701, respectively, in the WCH cohort, and 0.770, 0.739, and 0.743, respectively, in the FUSCC cohort. EPD may serve as a novel prognostic marker, allowing for the identification of a population with a poor prognosis in ER+/HER2- EBC, thereby aiding clinical decision-making.
| S-EPMC11489460 | biostudies-literature
Project description:The calcium-activated chloride channel Ano1 (TMEM16A) is overexpressed in many tumors. However, conflicting data exist regarding the role of Ano1 in cell proliferation. Here, we performed immunohistochemistry to investigate the expression of Ano1 and Ki67 in 403 patients with breast cancer, and analyzed the association between the expression of Ano1 and Ki67 in breast cancer subtypes categorized according to estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Ano1 expression was negatively correlated with Ki67 expression. Ano1 overexpression more frequently occurred in ER-positive or HER2-negative patients with the low expression of Ki67. Ano1 overexpression was associated with longer overall survival (OS) in breast cancer with the low expression of Ki67, especially in ER-positive, PR-positive, and HER2-negative breast cancer. Multivariate Cox regression analysis showed that Ano1 overexpression was a prognostic factor for longer overall survival in ER-positive, PR-positive, or HER2-negative patients with the low expression of Ki67. Furthermore, Ano1 promoted cell proliferation in ER-positive, PR-positive, and HER2-negative MCF7 cells, but inhibited cell proliferation in ER-negative, PR-negative, and HER2-negative MDA-MB-435S cells. Our findings suggest that Ano1 may differentially regulate cell proliferation in a subtype of breast cancer defined by ER, PR, and HER2. Combined expression of Ano1 and Ki67 may be used for predicting clinical outcomes of breast cancer patients with different subtypes of ER, PR, and HER2.
| S-EPMC5689589 | biostudies-literature
Project description:PurposeThe role of neoadjuvant chemotherapy (NAC) in node-positive (N+) ER+/HER2- breast cancer (BC) is debated, given low total pathologic complete response (pCR) rates. However, the rate and impact of nodal pCR is unknown. We sought to evaluate nodal pCR rates and the impact on overall survival (OS). Further, we sought to validate the association between nodal pCR with age and Ki67.MethodsWe queried the National Cancer Database for cN + ER+/HER2- BC patients treated with NAC and surgery. Data from 2010 to 2018 were used to evaluate nodal pCR and OS, with multivariable Cox proportional hazards modeling for OS, as well as Ki67 for the years 2018-2019.ResultsFrom 2010 to 2018, we identified 19,611 cN + ER+/HER2- BC patients treated with NAC. While total pCR occurred in only 7.4%, nodal pCR rates were nearly double (14.3%). Nodal pCR (+/- breast pCR) was seen in 21.7% and associated with 5-year OS rate of 86.1% (95% CI: 84.9-87.4%) versus 77.1% (95% CI: 76.3-77.9%) in patients without nodal pCR (p < 0.001). On multivariable analysis, nodal pCR had better OS (adjusted HR 0.57, 95% CI 0.52-0.63, p < 0.001) across all age groups. Of 2,444 patients with available Ki67, those with age < 50 and Ki67 ≥ 20% had the highest nodal pCR at 31.6%.ConclusionIn cN + ER+/HER2- BC treated with NAC, nodal pCR is common, associated with age and Ki67, and prognostic for OS. These data strongly suggest that for cN + patients, eradication of nodal disease is critical for OS, and total pCR may not be the optimal measure of NAC benefit.
| S-EPMC11385785 | biostudies-literature
Project description:Progesterone receptor (PR) is usually co-localized with estrogen receptor (ER) in normal mammary cells. It is not known whether ER/PR-negative human breast cancer arises from an ER/PR-negative cell or from an ER/PR-positive cell that later lost ER/PR. Using intraductal injection of a lentivirus to deliver both an oncogene (ErbB2) and a floxed green fluorescent protein (GFP) in PR(Cre/+)mice, whose Cre gene is under the control of the PR promoter, we were able to trace the PR status of the infected cells as they progressed to cancer. We found that the resulting early lesions stained negative for PR in most of the cells and usually retained GFP. The resulting tumors lacked ER and PR, and 75% (15/20) of them retained the GFP signal in all tumor cells, suggesting PR was never expressed throughout the evolution of a majority of these tumors. In conclusion, our data demonstrate that ErbB2-initiated ER/PR-negative mammary tumors primarily originate from the subset of the mammary epithelium that is negative for PR and probably ER as well. These findings also provide an explanation for why antihormonal therapy fails to prevent ER-negative breast cancers.
| S-EPMC5944622 | biostudies-literature
Project description:Breast cancers are categorized into three subtypes based on protein expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2/ERBB2). Patients enroll onto experimental clinical trials based on ER, PR, and HER2 status and, as receptor status is prognostic and defines treatment regimens, central receptor confirmation is critical for interpreting results from these trials. Patients enrolling onto experimental clinical trials in the metastatic setting often have limited available archival tissue that might better be used for comprehensive molecular profiling rather than slide-intensive reconfirmation of receptor status. We developed a Random Forests-based algorithm using a training set of 158 samples with centrally confirmed IHC status, and subsequently validated this algorithm on multiple test sets with known, locally determined IHC status. We observed a strong correlation between target mRNA expression and IHC assays for HER2 and ER, achieving an overall accuracy of 97 and 96%, respectively. For determining PR status, which had the highest discordance between central and local IHC, incorporation of expression of co-regulated genes in a multivariate approach added predictive value, outperforming the single, target gene approach by a 10% margin in overall accuracy. Our results suggest that multiplexed qRT-PCR profiling of ESR1, PGR, and ERBB2 mRNA, along with several other subtype associated genes, can effectively confirm breast cancer subtype, thereby conserving tumor sections and enabling additional biomarker data to be obtained from patients enrolled onto experimental clinical trials.
| S-EPMC4223539 | biostudies-literature
Project description:ER/PR+HER2- breast tumours are the most predominant subtype of breast cancer worldwide, including India. Unlike TNBCs, these tumours can be treated with anti-estrogens or aromatase inhibitors. Despite the success of endocrine therapy, a fraction of patients with ER/PR+ breast tumours do not respond to hormone-receptor-specific treatment and encounter disease recurrence contributing to their poor survival. The genomic underpinnings of therapy resistance in ER/PR+HER2- breast tumours are incompletely understood. We have performed whole genome sequencing (WGS) from tumour and normal tissue samples from endocrine-therapy resistant ER/PR+HER2- breast cancer patients who have relapsed on endocrine therapy and have conducted a comparative analysis of WGS data generated from tissues of endocrine therapy sensitive patients who remained free of disease during a minimum 5-year follow-up. Our analysis shows (a) a three-gene (PIK3CA-ESR1-TP53) resistance signature, and (b) impaired DNA double-strand break repair and homologous recombination pathways, were significantly associated with endocrine-therapy resistance and disease recurrence in ER/PR+HER2- tumours. Genome instability, contributing to high burden of copy-number, structural alterations and telomere-shortening identified as major markers of endocrine treatment resistance. Early prediction of endocrine-therapy resistance from the genomic landscape of breast tumours will aid therapeutics. Our finding also opens up the possibility of repurposing PARP inhibitors in treating endocrine therapy-resistant breast cancer patients.
| S-EPMC11811163 | biostudies-literature