Abstract:
BACKGROUND:The global observational BREAKOUT study investigated germline BRCA mutation (gBRCAm) prevalence in a population of patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). METHODS:Eligible patients had initiated first-line cytotoxic chemotherapy for HER2-negative MBC within 90 days prior to enrollment. Hormone receptor (HR)-positive patients had experienced disease progression on or after prior endocrine therapy, or endocrine therapy was considered unsuitable. gBRCAm status was determined using baseline blood samples or prior germline test results. For patients with a negative gBRCAm test, archival tissue was tested for somatic BRCAm and homologous recombination repair mutations (HRRm). Details of first-line cytotoxic chemotherapy were also collected. RESULTS:Between March 2017 and April 2018, 384 patients from 14 countries were screened and consented to study enrollment; 341 patients were included in the full analysis set (median [range] age at enrollment: 56 [25-89] years; 256 (75.3%) postmenopausal). Overall, 33 patients (9.7%) had a gBRCAm (16 [4.7%] in gBRCA1 only, 12 [3.5%] in gBRCA2 only, and 5 [1.5%] in both gBRCA1 and gBRCA2). gBRCAm prevalence was similar in HR-positive and HR-negative patients. gBRCAm prevalence was 9.0% in European patients and 10.6% in Asian patients and was higher in patients aged ≤ 50 years at initial breast cancer (BC) diagnosis (12.9%) than patients aged > 50 years (5.4%). In patients with any risk factor for having a gBRCAm (family history of BC and/or ovarian cancer, aged ≤ 50 years at initial BC diagnosis, or triple-negative BC), prevalence was 10.4%, versus 5.8% in patients without these risk factors. HRRm prevalence was 14.1% (n = 9/64) in patients with germline BRCA wildtype. CONCLUSIONS:Patient demographic and disease characteristics supported the association of a gBRCAm with younger age at initial BC diagnosis and family history of BC and/or ovarian cancer. gBRCAm prevalence in this cohort, not selected on the basis of risk factors for gBRCAm, was slightly higher than previous results suggested. gBRCAm prevalence among patients without a traditional risk factor for harboring a gBRCAm (5.8%) supports current guideline recommendations of routine gBRCAm testing in HER2-negative MBC, as these patients may benefit from poly(ADP-ribose) polymerase (PARP) inhibitor therapy. TRIAL REGISTRATION:NCT03078036 .
journal_name
Breast Cancer Resjournal_title
Breast cancer research : BCRauthors
O'Shaughnessy J,Brezden-Masley C,Cazzaniga M,Dalvi T,Walker G,Bennett J,Ohsumi Sdoi
10.1186/s13058-020-01349-9subject
Has Abstractpub_date
2020-10-27 00:00:00pages
114issue
1eissn
1465-5411issn
1465-542Xpii
10.1186/s13058-020-01349-9journal_volume
22pub_type
杂志文章,多中心研究abstract:BACKGROUND:Breast ductal carcinoma in situ (DCIS) represent approximately 20% of screen-detected breast cancers. The overall risk for DCIS patients treated with breast-conserving surgery stems almost exclusively from local recurrence. Although a mastectomy or adjuvant radiation can reduce recurrence risk, there are sig...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-019-1165-5
更新日期:2019-07-29 00:00:00
abstract::Over the past 8 years there has been a wealth of breast cancer gene expression studies. The majority of these studies have focused upon characterising a tumour at presentation, before treatment, rather than looking at the effects of treatment on the tumour. More recently, a number of groups have moved from predicting ...
journal_title:Breast cancer research : BCR
pub_type: 评论,社论
doi:10.1186/bcr2196
更新日期:2008-01-01 00:00:00
abstract::As the release of tumor-associated DNA into blood circulation is a common event in patients with cancer, screening of plasma or serum DNA may provide information on genetic and epigenetic profiles associated with breast cancer development, progression, and response to therapy. Quantitative testing of circulating DNA c...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/s13058-015-0645-5
更新日期:2015-10-09 00:00:00
abstract::Four trials of high-dose chemotherapy with stem cell support in breast cancer in the adjuvant and metastatic settings have shown no long-term disease-free or overall survival gain. This relative failure of a single high-dose therapy we believe opens up the development of a dose-dense approach with block scheduling as ...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr262
更新日期:2001-01-01 00:00:00
abstract:INTRODUCTION:Gene expression analysis is used to subtype breast cancers such that the most aggressive tumors are identified, but translating this into clinical practice can be cumbersome. Our goal is to develop a universal biomarker that distinguishes patients at high risk across all breast cancer subtypes. We previous...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr2156
更新日期:2008-01-01 00:00:00
abstract:INTRODUCTION:Incidence of breast cancer is increasing around the world and it is still the leading cause of cancer mortality in low- and middle-income countries. We utilized Swedish nationwide registers to study breast cancer incidence and case fatality to disentangle the effect of socioeconomic position (SEP) and immi...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr3086
更新日期:2012-01-06 00:00:00
abstract::Lobular carcinoma in situ (LCIS) is considered to be a risk factor for the development of invasive breast carcinoma, but it may also be a non-obligate precursor to invasive lobular carcinoma (ILC). Many LCIS lesions do not progress to ILC, and the molecular changes that are necessary for progression from LCIS to ILC a...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/s13058-015-0580-5
更新日期:2015-06-04 00:00:00
abstract:INTRODUCTION:Rapamycin, an inhibitor of the serine/threonine kinase target of rapamycin, induces G1 arrest and/or apoptosis. Although rapamycin and its analogues are attractive candidates for cancer therapy, their sensitivities with respect to growth inhibition differ markedly among various cancer cells. Using human br...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr1344
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND:In over 20% of breast conserving operations, postoperative pathological assessment of the excised tissue reveals positive margins, requiring additional surgery. Current techniques for intra-operative assessment of tumor margins are insufficient in accuracy or resolution to reliably detect small tumors. There...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-018-1002-2
更新日期:2018-07-09 00:00:00
abstract:INTRODUCTION:The ataxia telangiectasia mutated (ATM) gene is a tumor suppressor gene with functions in cell cycle arrest, apoptosis, and repair of DNA double-strand breaks. Based on family studies, women heterozygous for mutations in the ATM gene are reported to have a fourfold to fivefold increased risk of breast canc...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr809
更新日期:2004-01-01 00:00:00
abstract::RAD51C is an integral part of the DNA double-strand repair through homologous recombination, and monoallelic mutations were found in ~1.3% of BRCA1/2-negative breast cancer (BC) and/or ovarian cancer (OC) families. Several studies confirmed the occurrence of RAD51C mutations predominantly in BC and/or OC families, alt...
journal_title:Breast cancer research : BCR
pub_type: 信件
doi:10.1186/bcr3589
更新日期:2013-12-20 00:00:00
abstract:BACKGROUND:Dysregulated DNA repair and cell proliferation controls are essential driving forces in mammary tumorigenesis. BCCIP was originally identified as a BRCA2 and CDKN1A interacting protein that has been implicated in maintenance of genomic stability, cell cycle regulation, and microtubule dynamics. The aims of t...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-017-0907-5
更新日期:2017-10-18 00:00:00
abstract:INTRODUCTION:Despite advances in early detection and adjuvant targeted therapies, breast cancer is still the second most common cause of cancer mortality among women. Tumor recurrence is one of the major contributors to breast cancer mortality. However, the mechanisms underlying this process are not completely understo...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-015-0649-1
更新日期:2015-11-18 00:00:00
abstract:BACKGROUND:The BRCA1 c.3331_3334delCAAG founder mutation has been reported in hereditary breast and ovarian cancer families from multiple Hispanic groups. We aimed to evaluate BRCA1 c.3331_3334delCAAG haplotype diversity in cases of European, African, and Latin American ancestry. METHODS:BC mutation carrier cases from...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-020-01341-3
更新日期:2020-10-21 00:00:00
abstract:BACKGROUND:Vitamin D has been suggested to prevent and improve the prognosis of several cancers, including breast cancer. We have previously shown a U-shaped association between pre-diagnostic serum levels of vitamin D and risk of breast cancer-related death, with poor survival in patients with the lowest and the highe...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-019-1169-1
更新日期:2019-07-29 00:00:00
abstract:BACKGROUND:While dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) is recognized as the most sensitive examination for breast cancer detection, it has a substantial false positive rate and gadolinium (Gd) contrast agents are not universally well tolerated. As a result, alternatives to diagnosing breast can...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-017-0902-x
更新日期:2017-10-24 00:00:00
abstract:INTRODUCTION:Aberrant microenvironment and endoplasmic reticulum (ER) stress are associated with solid-tumor progression. Stress proteins, like heat shock proteins and glucose-regulated proteins, are frequently overexpressed in human tumors. It has been reported that derlin-1 is involved in ER stress response. In vitro...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr1849
更新日期:2008-01-01 00:00:00
abstract::Testosterone binds to the androgen receptor in target tissue to mediate its effects. Variations in testosterone levels and androgen receptor activity may play a role in the etiology of breast cancer. Here, we review the epidemiologic evidence linking endogenous testosterone to breast cancer risk. Paradoxically, result...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr593
更新日期:2003-01-01 00:00:00
abstract:BACKGROUND:Developing novel strategies against treatment-resistant triple negative breast cancer (TNBC) cells remains a significant challenge. The ErbB family, including epidermal growth factor receptor (EGFR), plays key roles in metastasis, tumorigenesis, cell proliferation, and drug resistance. Recently, these charac...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-015-0662-4
更新日期:2016-01-12 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: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:INTRODUCTION:Studies on the association between the cytochrome P450c17alpha gene (CYP17) 5'-untranslated region MspA1 genetic polymorphism and breast cancer risk have yielded inconsistent results. Higher levels of estrogen have been reported among young nulliparous women with the A2 allele. Therefore we assessed the im...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr1027
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND:Mammographic density (MD) is a strong and heritable intermediate phenotype of breast cancer, but much of its genetic variation remains unexplained. METHODS:We conducted a genetic association study of volumetric MD in a Swedish mammography screening cohort (n = 9498) to identify novel MD loci. Associations w...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-018-0954-6
更新日期:2018-04-17 00:00:00
abstract:INTRODUCTION:Breast cancer subtypes exhibit different genomic aberration patterns with a tendency for high-level amplifications in distinct chromosomal regions. These genomic aberrations may drive carcinogenesis through the upregulation of proto-oncogenes. We have characterized DNA amplification at the human chromosoma...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr2456
更新日期:2009-01-01 00:00:00
abstract::The metastatic process is a multistep coordinated event with a high degree of efficiency. Specific subpopulations of cancer stem cells, with tumor-initiating and migratory capacity, can selectively migrate towards sites that are able to promote survival and/or proliferation of metastatic tumor cells through a microenv...
journal_title:Breast cancer research : BCR
pub_type: 社论,评审
doi:10.1186/bcr2911
更新日期:2011-08-16 00:00:00
abstract::Improvements in the detection and treatment of breast cancer have dramatically altered its clinical course and outcome. However, prevention of breast cancer remains an elusive goal. Parity, age of menarche, and age at menopause are major risk factors drawing attention to the important role of the endocrine system in d...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr431
更新日期:2002-01-01 00:00:00
abstract:INTRODUCTION:AIB1, located at 20q12, is a member of the steroid hormone coactivator family. It contains a glutamine repeat (CAG/CAA) polymorphism at its carboxyl-terminal region that may alter the transcriptional activation of the receptor and affect susceptibility to breast cancer through altered sensitivity to hormon...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr1009
更新日期:2005-01-01 00:00:00
abstract:INTRODUCTION:The ataxia-telangiectasia mutated (ATM) gene (MIM ID 208900) encodes a protein kinase that plays a significant role in the activation of cellular responses to DNA double-strand breaks through subsequent phosphorylation of central players in the DNA damage-response pathway. Recent studies have confirmed tha...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,多中心研究
doi:10.1186/bcr2919
更新日期:2011-07-25 00:00:00
abstract::The protective effect of an early full-term pregnancy is a well established phenomenon; in contrast, the molecular and cell-specific mechanisms that govern parity-specific changes in the mammary gland have not been well described. Recent studies signify a dramatic advance in our understanding of this phenomenon, and i...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr603
更新日期:2003-01-01 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