Abstract:
BACKGROUND:Breast cancer subtype can be classified using standard clinical markers (estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2)), supplemented with additional markers. However, automated biomarker scoring and classification schemes have not been standardized. The aim of this study was to optimize tumor classification using automated methods in order to describe subtype frequency in the African American Breast Cancer Epidemiology and Risk (AMBER) consortium. METHODS:Using immunohistochemistry (IHC), we quantified the expression of ER, PR, HER2, the proliferation marker Ki67, and two basal-like biomarkers, epidermal growth factor receptor (EGFR) and cytokeratin (CK)5/6, in 1381 invasive breast tumors from African American women. RNA-based (prediction analysis of microarray 50 (PAM50)) subtype, available for 574 (42%) cases, was used to optimize classification. Subtype frequency was calculated, and associations between subtype and tumor characteristics were estimated using logistic regression. RESULTS:Relative to ER, PR and HER2 from medical records, central IHC staining and the addition of Ki67 or combined tumor grade improved accuracy for classifying PAM50-based luminal subtypes. Few triple negative cases (< 2%) lacked EGFR and CK5/6 expression, thereby providing little improvement in accuracy for identifying basal-like tumors. Relative to luminal A subtype, all other subtypes had higher combined grade and were larger, and ER-/HER2+ tumors were more often lymph node positive and late stage tumors. The frequency of basal-like tumors was 31%, exceeded only slightly by luminal A tumors (37%). CONCLUSIONS:Our findings indicate that automated IHC-based classification produces tumor subtype frequencies approximating those from PAM50-based classification and highlight high frequency of basal-like and low frequency of luminal A breast cancer in a large study of African American women.
journal_name
Breast Cancer Resjournal_title
Breast cancer research : BCRauthors
Allott EH,Geradts J,Cohen SM,Khoury T,Zirpoli GR,Bshara W,Davis W,Omilian A,Nair P,Ondracek RP,Cheng TD,Miller CR,Hwang H,Thorne LB,O'Connor S,Bethea TN,Bell ME,Hu Z,Li Y,Kirk EL,Sun X,Ruiz-Narvaez EA,Perou CMdoi
10.1186/s13058-018-0939-5subject
Has Abstractpub_date
2018-02-06 00:00:00pages
12issue
1eissn
1465-5411issn
1465-542Xpii
10.1186/s13058-018-0939-5journal_volume
20pub_type
杂志文章abstract:INTRODUCTION:Treatment with estrogen and progesterone (E+P) mimics the protective effect of parity on mammary tumors in rodents and depends upon the activity of p53. The following experiments tested whether exogenous E+P primes p53 to be more responsive to DNA damage and whether these pathways confer resistance to mamm...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr2094
更新日期:2008-01-01 00:00:00
abstract:BACKGROUND:Epidemiologic evidence suggests that certain dietary patterns were associated with breast cancer risk, but the results have been inconclusive. We assessed the associations between different dietary patterns and the risk of breast cancer by conducting a meta-analysis of observational studies. METHODS:Relevan...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,meta分析
doi:10.1186/s13058-019-1096-1
更新日期:2019-01-29 00:00:00
abstract::Array-based comparative genomic hybridization, RNA expression profiling, and proteomic analyses are new molecular technologies used to study breast cancer. Invasive breast cancers were originally evaluated because they provided ample quantities of DNA, RNA, and protein. The application of these technologies to pre-inv...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr655
更新日期:2003-01-01 00:00:00
abstract:INTRODUCTION:Human epidermal growth factor receptor HER3 has been implicated in promoting the aggressiveness and metastatic potential of breast cancer. Upregulation of HER3 has been found to be a major mechanism underlying drug resistance to EGFR and HER2 tyrosine kinase inhibitors and to endocrine therapy in the treat...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-015-0528-9
更新日期:2015-02-15 00:00:00
abstract:INTRODUCTION:The aim of this study was to describe breast tumor subtypes by common breast cancer risk factors and to determine correlates of subtypes using baseline data from two pooled prospective breast cancer studies within a large health maintenance organization. METHODS:Tumor data on 2544 invasive breast cancer c...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr2261
更新日期:2009-01-01 00:00:00
abstract:BACKGROUND:Full-field digital mammography (FFDM) has largely replaced film-screen mammography in the US. Breast density assessed from film mammograms is strongly associated with breast cancer risk, but data are limited for processed FFDM images used for clinical care. METHODS:We conducted a case-control study nested a...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-016-0715-3
更新日期:2016-05-21 00:00:00
abstract:INTRODUCTION:In 2001, data from the California Cancer Registry suggested that breast cancer incidence rates among non-Hispanic white (nHW) women in Marin County, California, had increased almost 60% between 1991 and 1999. This analysis examines the extent to which these and other breast cancer incidence trends could ha...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr1266
更新日期:2005-01-01 00:00:00
abstract::Genome-wide expression microarray studies have revealed that the biological and clinical heterogeneity of breast cancer can be partly explained by information embedded within a complex but ordered transcriptional architecture. Comprising this architecture are gene expression networks, or signatures, reflecting biochem...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr1662
更新日期:2007-01-01 00:00:00
abstract::ErbB (also termed HER) receptors are expressed in various tissues of epithelial, mesenchymal and neuronal origin, in which they are involved in the control of diverse biological processes such as proliferation, differentiation, migration and apoptosis. Furthermore, their deregulated expression has been implicated in m...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr327
更新日期:2001-01-01 00:00:00
abstract:INTRODUCTION:Epithelial-to-mesenchymal transition (EMT) promotes cell migration and is important in metastasis. Cellular proliferation is often downregulated during EMT, and the reverse transition (MET) in metastases appears to be required for restoration of proliferation in secondary tumors. We studied the interplay b...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr3580
更新日期:2013-11-27 00:00:00
abstract::For the past 20 years the mouse has served as a workhorse for studying the molecular underpinnings of human breast cancer. While some genetically engineered mouse mammary tumor models do not accurately recapitulate human disease (that is, the MMTV-Neu model and HER2-overexpressing human cancers), additional tumor mode...
journal_title:Breast cancer research : BCR
pub_type: 评论,社论
doi:10.1186/bcr2569
更新日期:2010-01-01 00:00:00
abstract:INTRODUCTION:Estrogen receptor-α (ER) and human epidermal growth factor receptor 2 (HER2) positivity are inversely correlated by standard criteria. However, we investigated the quantitative relation between ER and HER2 expression at both RNA and protein levels in HER2+ve and HER2-ve breast carcinomas. METHODS:ER and H...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,随机对照试验
doi:10.1186/bcr3145
更新日期:2012-03-14 00:00:00
abstract::Homeobox (HOX) genes play key roles in embryogenesis and tissue differentiation. Recently, a number of groups have reported altered HOX gene expression in breast cancer. However, the mechanism of HOX gene regulation and the search for direct targets of its transcriptional regulatory function have been minimally fruitf...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr2600
更新日期:2010-01-01 00:00:00
abstract::Epigenetic changes are critical for development and progression of cancers, including breast cancer. Significant progress has been made in the basic understanding of how various epigenetic changes such as DNA methylation, histone modification, miRNA expression, and higher order chromatin structure affect gene expressi...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr2925
更新日期:2011-01-01 00:00:00
abstract::c-Met is a receptor tyrosine kinase that upon binding of its ligand, hepatocyte growth factor (HGF), activates downstream pathways with diverse cellular functions that are important in organ development and cancer progression. Anomalous c-Met signalling has been described in a variety of cancer types, and the receptor...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/s13058-015-0547-6
更新日期:2015-04-08 00:00:00
abstract:INTRODUCTION:Breast tumors are comprised of distinct cancer cell populations which differ in their tumorigenic and metastatic capacity. Characterization of cell surface markers enables investigators to distinguish between cancer stem cells and their counterparts. CD24 is a well-known cell surface marker for mammary epi...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-015-0589-9
更新日期:2015-06-04 00:00:00
abstract:BACKGROUND:Tumor-derived extracellular vesicles (tdEVs) and circulating tumor cells (CTCs) in the blood of metastatic cancer patients associate with poor outcomes. In this study, we explored the human epidermal growth factor receptor 2 (HER2) expression on CTCs and tdEVs of metastatic breast cancer patients. METHODS:B...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-020-01323-5
更新日期:2020-08-12 00:00:00
abstract:INTRODUCTION:Radiation exposure at a young age is one of the strongest risk factors for breast cancer. Germline mutations in genes involved in the DNA-damage repair pathway (DDRP) may render women more susceptible to radiation-induced breast cancer. METHODS:We evaluated the contribution of germline mutations in the DD...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr1668
更新日期:2007-01-01 00:00:00
abstract:INTRODUCTION:We previously reported an association between tumor-specific 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR) expression and a good prognosis in breast cancer. Here, the predictive value of HMG-CoAR expression in relation to tamoxifen response was examined. METHODS:HMG-CoAR protein and RNA expr...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr2820
更新日期:2011-01-31 00:00:00
abstract:INTRODUCTION:Molecular apocrine (MA) tumors are estrogen receptor (ER) negative breast cancers characterized by androgen receptor (AR) expression. We analyzed a group of 58 transcriptionally defined MA tumors and proposed a new tool to identify these tumors. METHODS:We performed quantitative reverse transcription PCR ...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr3421
更新日期:2013-05-11 00:00:00
abstract:BACKGROUND:Breast cancer patients with early-stage disease are increasingly administered neoadjuvant chemotherapy (NAC) to downstage their tumors prior to surgery. In this setting, approximately 31% of patients fail to respond to therapy. This demonstrates the need for techniques capable of providing personalized feedb...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-020-01262-1
更新日期:2020-03-13 00:00:00
abstract:INTRODUCTION:Mammary-specific overexpression of Six1 in mice induces tumors that resemble human breast cancer, some having undergone epithelial to mesenchymal transition (EMT) and exhibiting stem/progenitor cell features. Six1 overexpression in human breast cancer cells promotes EMT and metastatic dissemination. We hyp...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr3219
更新日期:2012-07-05 00:00:00
abstract:BACKGROUND:Breast cancer is a heterogeneous disease. Hence, stratification of patients based on the subtype of breast cancer is key to its successful treatment. Among all the breast cancer subtypes, basal-like breast cancer is the most aggressive subtype with limited treatment options. Interestingly, we found focal adh...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-020-01298-3
更新日期:2020-06-03 00:00:00
abstract::Turnover of several regulatory proteins results from targeted destruction via ubiquitination and subsequent degradation through the proteosome. The timely and irreversible degradation of critical regulators is essential for normal cellular function. The precise biochemical mechanisms that are involved in protein turno...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr542
更新日期:2003-01-01 00:00:00
abstract:INTRODUCTION:Compromised patterns of gene expression result in genomic instability, altered patterns of gene expression and tumour formation. Specifically, aberrant DNA hypermethylation in gene promoter regions leads to gene silencing, whereas global hypomethylation events can result in chromosomal instability and onco...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr799
更新日期:2004-01-01 00:00:00
abstract:INTRODUCTION:Earlier menarche is related to subsequent breast cancer risk, yet international differences in the age and tempo of other pubertal milestones and their relationships with body mass index (BMI) are not firmly established in populations at differing risk for breast cancer. We compared age and tempo of adrena...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-014-0469-8
更新日期:2014-11-15 00:00:00
abstract:INTRODUCTION:Our efforts to prevent and treat breast cancer are significantly impeded by a lack of knowledge of the biology and developmental genetics of the normal mammary gland. In order to provide the specimens that will facilitate such an understanding, The Susan G. Komen for the Cure Tissue Bank at the IU Simon Ca...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr3627
更新日期:2014-03-17 00:00:00
abstract::This cross-sectional investigation in Hawaii explored the relation between soy foods and mammographic characteristics using two food frequency questionnaires and a computer-assisted density assessment method. Japanese and Chinese women reported significantly greater soy food intake than Caucasian women. Whereas soy in...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr285
更新日期:2001-01-01 00:00:00
abstract::Breast cancer arises from multiple genetic events that together contribute to the established, irreversible malignant phenotype. The development of inducible tissue-specific transgenics has allowed a careful dissection of the events required for induction and subsequent maintenance of tumorigenesis. Mammary gland targ...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr297
更新日期:2001-01-01 00:00:00
abstract::Progesterone and estradiol, and their nuclear receptors, play essential roles in the physiology of the reproductive tract, the mammary gland and the nervous system. Estrogens have traditionally been considered associated with an increased risk of breast cancer. There is, however, compelling evidence that progesterone ...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr539
更新日期:2002-01-01 00:00:00