Abstract:
:Poly(ADP-ribose) polymerase-1 (PARP1) is a key facilitator of DNA repair. PARP inhibitors have gained recent attention as promising therapeutic agents for the treatment of solid tumours including breast cancer (BC). However, the biological and clinical significance of PARP1 expression in BC and its role in DNA-damage response (DDR) remain to be defined. We investigated the expression of PARP1 expression, cleaved (PARP1c) and non-cleaved (PAR1nc) forms, in a large and well-characterised cohort of clinically annotated stage I-III operable BCs (n = 1,269) and 43 BRCA1-mutated BCs using immunohistochemistry. PARP1 expression was correlated to clinicopathological variables, outcome and expression of other key DNA repair proteins (BRCA1, RAD51, Ku70/80, PIASγ and CHK1). Expression of PARP1 was exclusively nuclear. 49 and 85 % of sporadic BC showed expression PARP1nc and PARP1c, respectively. In BRCA1-mutated tumours, PARP1nc/PARP1c was highly expressed (95 and 79 %, respectively). PARP1nc expression was positively associated with premenopausal younger age patients, larger size and higher tumour grade. PARP1 was positively associated with DDR-proteins; RAD51, BRCA1, CHK1 and PIASγ (p < 0.001). Negative association was found between PARP1nc and Ki67. PARP1c was associated with ER (p < 0.001). Different associations between PARP1 and DDR-proteins were observed when stratified based on ER/BRCA1 status. PARP1 was not an independent predictor of outcome in sporadic or BRCA1-mutated BC. Our results demonstrate a potential biological role for PARP1c and PARP1nc in DNA repair in BC based on the significant association with other key DNA damage repair proteins. These associations were not restricted to ER-negative or triple-negative subgroup.
journal_name
Breast Cancer Res Treatjournal_title
Breast cancer research and treatmentauthors
Green AR,Caracappa D,Benhasouna AA,Alshareeda A,Nolan CC,Macmillan RD,Madhusudan S,Ellis IO,Rakha EAdoi
10.1007/s10549-014-3230-1subject
Has Abstractpub_date
2015-01-01 00:00:00pages
353-62issue
2eissn
0167-6806issn
1573-7217journal_volume
149pub_type
杂志文章abstract::A novel region of amplification in breast tumors was recently identified on chromosome 17q23. Extensive mapping of the amplicon by Southern blotting and fluorescence in situ hybridization (FISH) in breast cancer cell lines determined that the amplicon can be up to 4 Mbp in size and may contain 50 genes. Copy number an...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,评审
doi:10.1023/a:1023081624133
更新日期:2003-04-01 00:00:00
abstract::Expression of the oestrogen producing enzyme, aromatase, is regulated in a tissue-specific manner by its encoding gene CYP19A1. In post-menopausal women, the major site for oestrogen production in the breast is the adipose, where CYP19A1 transcription is driven by the distal promoter I.4 (PI.4). Transcripts via this p...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-013-2413-5
更新日期:2013-02-01 00:00:00
abstract::Five-year breast cancer survivors, diagnosed after 65 years of age, may develop more incident comorbidities than similar populations free of cancer. We investigated whether older breast cancer survivors have a similar comorbidity burden 6-15 years after cancer diagnosis to matched women free of breast cancer at start ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-014-3021-8
更新日期:2014-07-01 00:00:00
abstract::Bone lesions as a consequence of bone metastases in breast cancer patients can increase risk for skeletal-related events (SREs) (i.e., radiation to the bone, a pathological or osteoporotic fracture event, hypercalcemia, spinal cord compression, or surgery to the bone). The mortality risk for breast cancer patients wit...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-011-1475-5
更新日期:2011-09-01 00:00:00
abstract:PURPOSE:The role of sentinel lymph node biopsy (SLNB) in breast cancer patients who undergo neoadjuvant chemotherapy (NAC) remains controversial. This study aims to investigate if axillary lymph node dissection (ALND) could be safely omitted after a negative SLNB in cN1/2 patients who become cN0 after NAC. METHODS:We ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-020-06011-8
更新日期:2020-11-09 00:00:00
abstract:BACKGROUND:The estrogen receptor alpha (ESR1) is a mediator of estrogen response in the breast. The most studied variants in this gene are the PvuII and XbaI polymorphisms, which have been associated to lower sensitivity to estrogen. We evaluated whether these polymorphisms were associated with breast cancer risk by me...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-007-9562-3
更新日期:2008-02-01 00:00:00
abstract:BACKGROUND:Clearance of large molecules from the interstitial space is an important function of lymphatics and is affected by local pathologic changes. OBJECTIVE:To determine if the clearance rate of interstitially injected albumin is correlated to tumour characteristics and outcome in women with invasive breast cance...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1005749825449
更新日期:1997-01-01 00:00:00
abstract::Review of comparative pathology studies of breast cancer among Japanese women and other ethnic groups reveals consistent differences in tumor morphology and host response. Japanese women show lower rates of breast cancer than Caucasian women, a difference that is accounted for by increased rates of this cancer in post...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,评审
doi:10.1007/BF02633531
更新日期:1991-05-01 00:00:00
abstract:BACKGROUND:Estimating an individual woman's absolute risk for breast cancer is essential for decision making about screening and preventive recommendations. Although the current standard, the Gail model, is well calibrated in populations, it performs poorly for individuals. Mammographic breast density (BD) may improve ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-005-5152-4
更新日期:2005-11-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-013-2617-8
更新日期:2013-07-01 00:00:00
abstract:PURPOSE:Breast terminal duct lobular units undergo two distinctive physiological processes of involution: age-related lobular involution (LI), which is gradual and associated with decreased breast cancer risk, and postlactational involution, which is relatively precipitous, occurs with weaning, and has been associated ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-017-4413-3
更新日期:2017-11-01 00:00:00
abstract::Recent compelling evidence indicates that mutation, aberrant expression, and dysregulation of microRNA (miRNA) biogenesis are implicated in cancer development and progression. Based on the important role of miRNA biogenesis pathway in carcinogenesis, we hypothesized that genetic variations in this pathway genes may pl...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-011-1656-2
更新日期:2011-12-01 00:00:00
abstract::The tumor-stroma ratio has previously been shown to be prognostic for patients with invasive breast cancer. We present a validation study to assess the prognostic significance in lymph node-negative, premenopausal patients from the perioperative chemotherapy trial (POP trial, 10854) conducted by the European Organizat...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-013-2571-5
更新日期:2013-06-01 00:00:00
abstract:PURPOSE:Cyclin D1 has a central role in cell cycle control and is an important component of estrogen regulation of cell cycle progression. We have previously shown that high cyclin D expression is related to aggressive features of ER-positive but not ER-negative breast cancer. The aims of the present study were to vali...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-017-4294-5
更新日期:2017-08-01 00:00:00
abstract::Clinical practice guidelines recommend yearly surveillance mammography for breast cancer survivors, yet many women do not receive this service. The objective of this study was to evaluate factors related to long-term surveillance mammography adherence among breast cancer survivors. We conducted a retrospective cohort ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-013-2816-3
更新日期:2014-02-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-014-2999-2
更新日期:2014-07-01 00:00:00
abstract::Intraoperative radiotherapy with electrons (ELIOT) after conservative surgery for breast carcinoma was introduced at the IEO in 1999 as a research programme. The results on 1,822 patients treated from January 2000 to December 2008 are reported. Women with unicentric primary breast carcinoma of less than 2.5 cm in the ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-010-1115-5
更新日期:2010-11-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-004-5783-x
更新日期:2005-05-01 00:00:00
abstract::The Women's Health Initiative (WHI) randomized trials found that use of combined estrogen and progestin menopausal hormone therapy (CHT) increases breast cancer risk, but use of unopposed estrogen hormone therapy (EHT) does not. However, several questions regarding the impact of hormone use on risk of different types ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-014-2960-4
更新日期:2014-06-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-019-05216-w
更新日期:2019-07-01 00:00:00
abstract::Our previous studies have shown that social housing conditions can significantly alter the growth rate of the Shionogi mouse mammary carcinoma (SC115). The present study extended our investigations to the molecular level by examining stressor effects on the expression of a group of stress-responsive proteins, the heat...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1006314010958
更新日期:2000-02-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-011-1864-9
更新日期:2012-06-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-016-3838-4
更新日期:2016-06-01 00:00:00
abstract::Cytochrome P450s are enzymes which catalyze Phase-I metabolism reactions; cytochrome P450 1A1 (CYP1A1) is a member of the CYP1 family and participates in the metabolism of a vast number of xenobiotics, as well as endogenous substrates. Four single nucleotide polymorphisms in CYP1A1 have been studied concerning their p...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,meta分析,评审
doi:10.1007/s10549-009-0694-5
更新日期:2010-07-01 00:00:00
abstract::Previous studies on breast cancer recurrence provide a mixed picture of the quality of life of women following a recurrence. To clarify the picture, the present study addresses some previous methodological concerns by offering a multidimensional assessment with follow-up, a matched comparison group of disease-free sur...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/B:BREA.0000041580.55817.5a
更新日期:2004-09-01 00:00:00
abstract::In previous studies we demonstrated that rat mammary tumor (RMT) cells that are serially transplantable consist of cells that are independent of growth factors strictly required by normal rat mammary epithelial (RME) cells for growth in serum-free culture. The present studies were designed to determine the extent of t...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF01980969
更新日期:1991-05-01 00:00:00
abstract:PURPOSE:To determine if response to endocrine therapy of breast cancer can be predicted by either a metabolic "flare reaction" detected by positron emission tomography (PET) with 2-[(18)F]-fluoro-2-deoxyglucose (FDG), induced by an estradiol challenge, or by estrogen-receptor (ER) status, determined by PET with the est...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-008-9953-0
更新日期:2009-02-01 00:00:00
abstract::Recent breast cancer treatment studies conducted in large urban settings have reported racial disparities in the appropriate use of adjuvant chemotherapy. This article presents the first focused evaluation of black-white differences in receipt and completion of chemotherapy for breast cancer in a primarily rural regio...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-011-1916-1
更新日期:2012-05-01 00:00:00
abstract::Decreased CYP2D6 activity is associated with lower levels of active tamoxifen metabolites. We examined the impact of CYP2D6 genotype on tamoxifen pharmacokinetics, biomarker activity, and efficacy in a pooled analysis of low-dose tamoxifen. Four randomized breast cancer prevention trials of very-low-dose (1 mg/day, n ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-016-3932-7
更新日期:2016-08-01 00:00:00
abstract::The aim of this study was to compare the effects on health-related quality of life (HRQOL) of two treatment regimens in the TEX trial during 9 month from random assignment, with emphasis on the 2- and 9-months assessments. A total of 287 patients were randomized to treatment in 3-week cycles with either epirubicin plu...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1007/s10549-010-1084-8
更新日期:2010-10-01 00:00:00