Abstract:
:The mutation pattern of breast cancer molecular subtypes is incompletely understood. The purpose of this study was to identify mutations in genes that may be targeted with currently available investigational drugs in the three major breast cancer subtypes (ER+/HER2-, HER2+, and Triple Negative). We extracted DNA from fine needle aspirations of 267 stage I-III breast cancers. These tumor specimens typically consisted of >80% neoplastic cells. We examined 28 genes for 163 known cancer-related nucleic acid variations by Sequenom technology. We observed at least one mutation in 38 alleles corresponding to 15 genes in 108 (40%) samples, including PIK3CA (16.1% of all samples), FBXW7 (8%), BRAF (3.0%), EGFR (2.6%), AKT1 and CTNNB1 (1.9% each), KIT and KRAS (1.5% each), and PDGFR-α (1.1%). We also checked for the polymorphism in PHLPP2 that is known to activate AKT and it was found at 13.5% of the patient samples. PIK3CA mutations were more frequent in estrogen receptor-positive cancers compared to triple negative breast cancer (TNBC) (19 vs. 8%, p=0.001). High frequency of PIK3CA mutations (28%) were also found in HER2+ breast tumors. In TNBC, FBXW7 mutations were significantly more frequent compared to ER+ tumors (13 vs. 5%, p=0.037). We performed validation for all mutated alleles with allele-specific PCR or direct sequencing; alleles analyzed by two different sequencing techniques showed 95-100% concordance for mutation status. In conclusion, different breast cancer subtypes harbor different type of mutations and approximately 40 % of tumors contained individually rare mutations in signaling pathways that can be potentially targeted with drugs. Simultaneous testing of many different mutations in a single needle biopsy is feasible and allows the design of prospective clinical trials that could test the functional importance of these mutations in the future.
journal_name
Breast Cancer Res Treatjournal_title
Breast cancer research and treatmentauthors
Santarpia L,Qi Y,Stemke-Hale K,Wang B,Young EJ,Booser DJ,Holmes FA,O'Shaughnessy J,Hellerstedt B,Pippen J,Vidaurre T,Gomez H,Valero V,Hortobagyi GN,Symmans WF,Bottai G,Di Leo A,Gonzalez-Angulo AM,Pusztai Ldoi
10.1007/s10549-012-2035-3subject
Has Abstractpub_date
2012-07-01 00:00:00pages
333-43issue
1eissn
0167-6806issn
1573-7217journal_volume
134pub_type
杂志文章abstract::A major goal of cancer chemotherapy is the identification of cytotoxic compounds that are highly selective for cancer cells. We describe here one such compound - a novel iron chelator, desferri-exochelin 772SM. This desferri-exochelin has unique chemical and pharmacological properties, including extremely high iron bi...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1012211828319
更新日期:2001-09-01 00:00:00
abstract::Breast cancer is a heterogeneous entity composed of distinct molecular subgroups with different molecular and clinical features. We analyzed the association between molecular breast cancer subgroups, age at diagnosis, and prognosis in a compilation of publicly available gene expression datasets. Affymetrix gene expres...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-015-3491-3
更新日期:2015-08-01 00:00:00
abstract:OBJECTIVE:To determine whether fruit, vegetable, and micronutrient intake 1 year prior to breast cancer diagnosis is associated with a reduction in the subsequent risk of all-cause or breast cancer-specific mortality. METHODS:Follow-up data from 1,235 invasive breast cancer cases age 25-98 years from the Long Island B...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-005-9150-3
更新日期:2006-07-01 00:00:00
abstract:PURPOSE:Inflammatory breast cancer (IBC) is the most aggressive form of locally advanced breast cancer (LABC). The IBC phenotype is characterized by an infiltrative growth pattern, increased (lymph)angiogenesis and the propensity to invade dermal lymphatics. In pancreatic cancer, interactions between caveolin-1 and Rho...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-005-9002-1
更新日期:2006-02-01 00:00:00
abstract::We aimed to analyse the impact of breast cancer (BC) subtypes on the clinical course of disease with special emphasis on the occurrence of brain metastases (BM) and outcome in an elderly BC population. A total number of 706 patients ≥65 years receiving treatment for BC from 2007 to 2011 were identified from a BC datab...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-016-3787-y
更新日期:2016-05-01 00:00:00
abstract:BACKGROUND:High insulin levels have been associated with poor outcomes in breast cancer. Our goal was to investigate whether hyperinsulinemia was associated with insulin resistance in a cohort of newly diagnosed locoregional breast cancer patients and to examine associations of hyperinsulinemia with the broader insulin...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-008-0019-0
更新日期:2009-04-01 00:00:00
abstract:PURPOSE:The results of studies comparing survival in familial and sporadic breast cancer (BC) are inconsistent. A higher incidence of contralateral breast cancer (CBC) has been reported in familial BC. Ascertainment bias may influence both the reported familial CBC and survival. DESIGN:We assessed CBC incidence, dista...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-005-9054-2
更新日期:2006-01-01 00:00:00
abstract::Interleukin-6 (IL-6) and interleukin-11 (IL-11) are frequently produced by breast cancer cells. These interleukins promote osteoclast formation and may mediate osteolysis at the site of breast cancer bone metastases. Transforming growth factor-beta (TGF-beta), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1b...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1024443303436
更新日期:2003-07-01 00:00:00
abstract:PURPOSE:Cytokine milieu of tumor microenvironment affects tumorigenesis in breast cancer. The aim of the present study was to investigate the potential association of functional single nucleotide polymorphisms (SNPs) in TNF-LTA locus with breast cancer. METHODS:The study included 127 individuals comprising 40 breast c...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-008-0006-5
更新日期:2009-03-01 00:00:00
abstract:PURPOSE:The effect of tea consumption on breast cancer survival remained to be explored. Meanwhile, green tea favorably facilitates lipid metabolisms in breast cancer survivors. This study aimed to examine the effect of tea consumption and the interactions with lipids on breast cancer survival. METHODS:A total of 1551...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-019-05253-5
更新日期:2019-08-01 00:00:00
abstract::The early spread of tumor cells in primary breast cancer patients may occur either through lymphatic or hematogenous dissemination. Lymph node (LN) status and presence of disseminated tumor cells (DTC) in bone marrow (BM) are independent predictors of poor outcome. It is unknown which factors determine one or the othe...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-011-1802-x
更新日期:2012-01-01 00:00:00
abstract::Alcohol consumption is known to be a risk factor for breast cancer in Western countries, but few epidemiologic data have been available in Japan. This population-based prospective cohort study evaluated the associations of alcohol consumption with breast cancer risk in a Japanese population. A total of 19,227 women ag...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-011-1381-x
更新日期:2011-08-01 00:00:00
abstract::Numerous studies have demonstrated that angiogenesis and in particular VEGF over-expression play an essential role in the progression and metastatic potential of breast cancer. Bevacizumab is a humanized recombinant monoclonal antibody that specifically blocks the binding of VEGF to high-affinity receptors and it has ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,meta分析,评审
doi:10.1007/s10549-009-0727-0
更新日期:2010-07-01 00:00:00
abstract::Early and late effects of cancer treatment are of increasing concern with growing survivor populations, but relevant data are sparse. We sought to determine the prevalence and hazard ratio of such effects in breast cancer cases. Women with invasive breast cancer and women with no cancer history recruited for a cancer ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-014-2928-4
更新日期:2014-05-01 00:00:00
abstract::There are divergent opinions regarding the optimum surgical management of the axilla in patients with invasive breast cancer. Guidelines mandate axillary lymph node dissection (ALND) in the setting of positive sentinel lymph nodes. However, recent studies have questioned the true benefits of this procedure. Therefore,...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,meta分析,评审
doi:10.1007/s10549-015-3549-2
更新日期:2015-09-01 00:00:00
abstract::To date, three molecular markers (ER, PR, and CYP2D6) have been used in clinical setting to predict the benefit of the anti-estrogen tamoxifen therapy. Our aim was to validate new biomarker candidates predicting response to tamoxifen treatment in breast cancer by evaluating these in a meta-analysis of available transc...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,meta分析
doi:10.1007/s10549-013-2622-y
更新日期:2013-07-01 00:00:00
abstract::The contribution of BRCA1 and BRCA2 to breast cancer incidence in Brazil has not yet been explored. In order to estimate the proportion of breast cancers due to BRCA1 and BRCA2 mutations in Brazil, we conducted a study of unselected breast cancer patients from Rio de Janeiro, Brazil. We enrolled 402 women with breast ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-006-9378-6
更新日期:2007-07-01 00:00:00
abstract::Thrombospondin-1 (TSP-1) has been proposed to have both pro-metastatic and anti-metastatic properties. To elucidate its role in breast cancer metastasis, we compared tumor progression in the polyomavirus middle T antigen (Pyt) transgenic mouse and the TSP-1-null Pyt transgenic mouse. We characterized the tumors in the...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-008-9992-6
更新日期:2009-03-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1023351717408
更新日期:2003-05-01 00:00:00
abstract::Sentinel lymph node (SLN) biopsy is rapidly emerging as an alternative to axillary lymph node dissection (ALND) for many female breast cancer patients. In contrast, ALND remains the standard of care for male breast cancer patients with similar tumors. We evaluated the results of SLN biopsy in male breast cancer patien...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1021173902253
更新日期:2003-01-01 00:00:00
abstract::In the present report, we retrospectively analyzed the impact of the timing of surgery during menstrual cycle on disease-free and overall survival of 248 premenopausal patients with stage I/II breast cancer who underwent surgery followed by anthracycline-containing adjuvant chemotherapy. With a median follow-up of 5 y...
journal_title:Breast cancer research and treatment
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
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更新日期:1999-06-01 00:00:00
abstract::The ability of the antiangiogenic agents TNP-470 and minocycline, singly or in combination, to potentiate the antitumor effects of several cytotoxic therapies was assessed in the murine EMT-6 mammary carcinoma as well as in two drug resistant sublines of that tumor designated EMT-6/CTX and EMT-6/CDDP. The antiangiogen...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF00666043
更新日期:1995-01-01 00:00:00
abstract::Women with reduced CYP2D6 activity have low endoxifen concentrations and likely worse long term benefits from tamoxifen. We investigated the association between CYP2D6 genotype and tamoxifen-induced hot flashes in a prospective cohort. We collected hot flash frequency and severity data over 12 months from 297 women in...
journal_title:Breast cancer research and treatment
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1007/s10549-009-0309-1
更新日期:2009-10-01 00:00:00
abstract:PURPOSE:Despite numerous studies on the utility of GATA-3 as breast cancer marker, its comparison with other breast markers, its concordance between primary and metastatic tumors and its expression in primary cancers from sites with frequent breast metastases remains unclear. METHODS:To address these questions, totall...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-017-4645-2
更新日期:2018-05-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-019-05376-9
更新日期:2019-11-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-008-0003-8
更新日期:2009-03-01 00:00:00
abstract::The anti-estrogenic effect of tamoxifen is suggested to be mainly attributable to its metabolite (Z)-endoxifen, and a minimum therapeutic threshold for (Z)-endoxifen in serum has been proposed. The objective of this research was to establish the relationship between dried blood spot (DBS) and serum concentrations of t...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-014-2999-2
更新日期:2014-07-01 00:00:00
abstract::The Breast Imaging Reporting and Data System (BI-RADS) was introduced in 1993 to standardize the interpretation of mammograms. Though many studies have assessed the validity of the system, fewer have examined its reliability. Our objective is to identify predictors of reliability as measured by the kappa statistic. We...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,评审
doi:10.1007/s10549-010-0770-x
更新日期:2010-04-01 00:00:00
abstract::Weight gain is a common problem amongst women receiving adjuvant chemotherapy for early breast cancer. We undertook a study to determine the causes of this weight gain. Prospective measurements of body mass and composition (skinfolds, bioelectrical impedance, total body potassium), energy balance (resting energy expen...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/B:BREA.0000014037.48744.fa
更新日期:2004-02-01 00:00:00
abstract::The c.156_157insAlu BRCA2 mutation has so far only been reported in hereditary breast/ovarian cancer (HBOC) families of Portuguese origin. Since this mutation is not detectable using the commonly used screening methodologies and must be specifically sought, we screened for this rearrangement in a total of 5,443 suspec...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-010-1036-3
更新日期:2011-06-01 00:00:00