Abstract:
:Metformin may reduce the incidence of breast cancer and enhance response to neoadjuvant chemotherapy in diabetic women. This trial examined the effects of metformin on Ki67 and gene expression in primary breast cancer. Non-diabetic women with operable invasive breast cancer received pre-operative metformin. A pilot cohort of eight patients had core biopsy of the cancer at presentation, a week later (without treatment; internal control), then following metformin 500-mg o.d. for 1 week increased to 1-g b.d. for a further week continued to surgery. A further 47 patients had core biopsy at diagnosis were randomized to metformin (the same dose regimen) or no drug, and 2 weeks later had core biopsy at surgery. Ki67 immunohistochemistry, transcriptome analysis on formalin-fixed paraffin-embedded cores and serum insulin determination were performed blinded to treatment. Seven patients (7/32, 21.9%) receiving metformin withdrew because of gastrointestinal upset. The mean percentage of cells staining for Ki67 fell significantly following metformin treatment in both the pilot cohort (P = 0.041, paired t-test) and in the metformin arm (P = 0.027, Wilcoxon rank test) but was unchanged in the internal control or metformin control arms. Messenger RNA expression was significantly downregulated by metformin for PDE3B (phosphodiesterase 3B, cGMP-inhibited; a critical regulator of cAMP levels that affect activation of AMP-activated protein kinase, AMPK), confirmed by immunohistochemistry, SSR3, TP53 and CCDC14. By ingenuity pathway analysis, the tumour necrosis factor receptor 1 (TNFR1) signaling pathway was most affected by metformin: TGFB and MEKK were upregulated and cdc42 downregulated; mTOR and AMPK pathways were also affected. Gene set analysis additionally revealed that p53, BRCA1 and cell cycle pathways also had reduced expression following metformin. Mean serum insulin remained stable in patients receiving metformin but rose in control patients. This trial presents biomarker evidence for anti-proliferative effects of metformin in women with breast cancer and provides support for therapeutic trials of metformin.
journal_name
Breast Cancer Res Treatjournal_title
Breast cancer research and treatmentauthors
Hadad S,Iwamoto T,Jordan L,Purdie C,Bray S,Baker L,Jellema G,Deharo S,Hardie DG,Pusztai L,Moulder-Thompson S,Dewar JA,Thompson AMdoi
10.1007/s10549-011-1612-1subject
Has Abstractpub_date
2011-08-01 00:00:00pages
783-94issue
3eissn
0167-6806issn
1573-7217journal_volume
128pub_type
临床试验,杂志文章,随机对照试验abstract::Studies from Western countries have found evidence of a recent decline in breast cancer incidence rates in postmenopausal women, findings which have been hypothesized to reflect a reduced use of hormonal replacement therapy (HRT). We examined breast cancer incidence trends in Sweden between 1997 and 2007, a period cha...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-009-0615-7
更新日期:2010-06-01 00:00:00
abstract::Genetic testing enables women at risk for hereditary breast and/or ovarian cancer to find out whether they have inherited the gene mutation (BRCA1/BRCA2), and if so, to opt for frequent surveillance and/or prophylactic surgery (bilateral mastectomy and/or oophorectomy). Here, a follow-up is described for 63 healthy wo...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1015269620265
更新日期:2002-05-01 00:00:00
abstract::A study has been conducted to compare the nature and severity of post-operative sensory changes (sensory loss, paraesthesiae, and pain) among patients with breast cancer treated by either modified radical mastectomy or a conservative procedure (tumourectomy, axillary clearance, iridium implant, and external radiothera...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF01805925
更新日期:1986-01-01 00:00:00
abstract::The aromatase inhibitors exemestane and anastrozole are approved in Japan for first-line treatment of postmenopausal patients with advanced, hormone-receptor-positive breast cancer. This phase 3, randomized, double-blind study directly compared time to progression (TTP) for exemestane and anastrozole therapy in this p...
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/s10549-013-2573-3
更新日期:2013-06-01 00:00:00
abstract::Feulgen-stained samples from 460 small (pT1) primary breast cancers were investigated by means of an image analysis system. Several DNA, morphometrical and textural parameters were evaluated for each patient, and the prognostic meaning of these parameters was then investigated by the Cox regression analysis. As progno...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF00690188
更新日期:1995-01-01 00:00:00
abstract::Photodynamic therapy (PDT) is a minimally invasive, FDA-approved therapy for treatment of endobronchial and esophageal cancers that are accessible to light. Inflammatory breast cancer (IBC) is an aggressive and highly metastatic form of breast cancer that spreads to dermal lymphatics, a site that would be accessible t...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-015-3618-6
更新日期:2015-11-01 00:00:00
abstract::Digital breast tomosynthesis (DBT) is emerging as the new standard of care for breast cancer screening based on improved cancer detection coupled with reductions in recall compared to screening with digital mammography (DM) alone. However, many prior studies lack follow-up data to assess false negatives examinations. ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-016-3695-1
更新日期:2016-02-01 00:00:00
abstract::We have previously shown that human breast carcinoma cells demonstrating an interconverted phenotype, where keratin (epithelial marker) and vimentin (mesenchymal marker) intermediate filaments are both expressed, have an increased ability to invade a basement membrane matrix in vitro. This increase in invasive potenti...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1006188129423
更新日期:1999-05-01 00:00:00
abstract::The purpose of the present study was to characterize primitive epithelial progenitor populations present in adult normal human mammary tissue using a combination of flow cytometry and in vitro colony assay procedures. Three types of human breast epithelial cell (HBEC) progenitors were identified: luminal-restricted, m...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1010615124301
更新日期:2001-05-01 00:00:00
abstract::Mastopathy is a common disease of the breast likely associated with elevated estrogen levels and a putative risk factor for breast cancer. The role of estrogen receptor alpha (ESR1) in mastopathy has not been investigated previously. Here, we investigated the prevalence of ESR1 gene amplification in mastopathy and its...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-015-3427-y
更新日期:2015-06-01 00:00:00
abstract::Heregulin (HRG) and 17beta-estradiol (E2) interactions that modulate growth of breast cancer cell lines have recently been demonstrated. We examined the ability of heregulin beta1 (HRGbeta1) and 17beta-estradiol to modulate the biological behavior of estrogen receptor (ER) negative human breast cancer cell lines (AU-5...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1006035603635
更新日期:1998-09-01 00:00:00
abstract::Number of mitoses and EGF binding were determined in parallel in biopsies of 27 lymph-node positive and of 23 lymph-node negative breast cancer patients. For node-positive patients the parameters for cell growth and EGF binding were quantitatively correlated by the equation y = P3 + P1(1- exp(- P2x]. For node-negative...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF01805739
更新日期:1988-09-01 00:00:00
abstract::PIN1, an isomerase that causes conformational changes in proteins, plays an important role in mammary epithelial cell growth both physiologically and pathologically. Thus, genetic variants in the PIN1 gene may alter protein function and cancer risk. We have previously demonstrated an association between a PIN1 promote...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-009-0682-9
更新日期:2010-07-01 00:00:00
abstract:BACKGROUND:This trial studied the disease-free survival after high-dose chemotherapy in patients in complete remission of metastatic breast cancer. PATIENTS AND METHODS:Thirty women, mean age 42.2 years (range 33-55) with metastatic breast cancer, received high-dose chemotherapy in a phase II study. Patients were elig...
journal_title:Breast cancer research and treatment
pub_type: 临床试验,杂志文章
doi:10.1007/BF01806158
更新日期:1996-01-01 00:00:00
abstract:PURPOSE:Many women with early-onset breast cancer experience adverse psychological sequelae which impact on their quality of life. We sought to correlate levels of anxiety and cancer-related distress in women with breast cancer shortly after surgery and one year after treatment with the estimated risk of death. METHOD...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-020-05992-w
更新日期:2020-11-10 00:00:00
abstract::The relationship between IGF genotypes and phenotypes in breast tumors and their associations with breast cancer risk remain to be elucidated. Such information is especially scarce in Chinese women. To evaluate IGF-I and IGFBP-3 genotypes in relation to their phenotypes in local breast tissues and in association with ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-011-1552-9
更新日期:2011-11-01 00:00:00
abstract::The structure/activity relationships for inhibition of aromatase and cholesterol side-chain cleavage enzyme (CSCC) by aminoglutethimide and some of its analogues are reviewed. Although more effective against aromatase than CSCC, aminoglutethimide markedly inhibits both enzymes. Optimal competitive antagonism of aromat...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:
更新日期:1986-01-01 00:00:00
abstract::Several authors question the potential benefit of preoperative magnetic resonance imaging (MRI) against the background of possible overdiagnosis, false-positive findings, and unnecessary resections in patients with newly diagnosed breast cancer. In order to reveal a better selection of patients who should undergo preo...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-015-3556-3
更新日期:2015-10-01 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::Transforming growth factor-β1 (TGF-β1) is negative regulator of cell proliferation and the cell cycle, and plasma levels of TGF-β1 are twice as high in TGF-β1 -509 T homozygotes as in -509 C homozygotes. Published studies on the association between the TGF-β1 gene -509 C/T polymorphism and breast cancer risk are incon...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,meta分析
doi:10.1007/s10549-010-0871-6
更新日期:2010-11-01 00:00:00
abstract::To investigate the prognostic value of tumor markers, cancer antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA) levels at diagnosis of systemic recurrence. After primary treatments of locoregional breast cancers, serum CA 15-3 and/or CEA concentrations were regularly measured, and systemic recurrences were iden...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-013-2695-7
更新日期:2013-10-01 00:00:00
abstract:INTRODUCTION:The current standard of treatment for non-palpable breast cancers is wire-guided localization (WGL). WGL has its drawbacks and alternatives such as radio-guided surgery (RGL) and intra-operative ultrasound (IOUS) have been developed. The clinical effectiveness of all forms of RGL has been assessed against ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,meta分析,评审
doi:10.1007/s10549-013-2639-2
更新日期:2013-08-01 00:00:00
abstract::Tumour hypoxia, being widespread in solid tumours, is related to an increased risk of invasion and metastasis as well as to resistance to chemotherapy and radiotherapy. Hypoxia-inducible factor-1alpha (HIF-1alpha) has emerged as the key regulator of the cellular response to hypoxia. In primary breast cancers, HIF-1alp...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-007-9589-5
更新日期:2008-03-01 00:00:00
abstract::Complete remissions in patients with metastatic breast cancer using endocrine therapy or chemotherapy are infrequent. Breast tumors are known to be heterogeneous with respect to estrogen receptor status, and the low complete remission rate may be related to this biochemical heterogeneity. Based on laboratory experimen...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF01805721
更新日期:1982-01-01 00:00:00
abstract::The diagnosis and treatment of patients with breast cancer is beginning to be influenced by new ideas and discoveries emerging from the field of angiogenesis research. This field, pursued in the laboratory for more than 20 years, has in the past 5 years generated clinical applications. Some of these applications have ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,评审
doi:10.1007/BF00666033
更新日期:1995-01-01 00:00:00
abstract::Following mastectomy, patients with operable breast cancer underwent postoperative irradiation of the chest wall and regional lymph nodes. They were then assigned at random to receive no further therapy, ovarian irradiation (2000 rad in five days) or ovarian irradiation in the same dosage plus prednisone, 7.5 mg daily...
journal_title:Breast cancer research and treatment
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF01855127
更新日期:1983-01-01 00:00:00
abstract::We have compared the effects of the progestin R5020 and the antiprogestin RU486 on the growth of the MCF-7 and T47D breast cancer cell lines. Differences between the two compounds were demonstrated in several parameters. 1. Estradiol was required for the efficient inhibition of cell growth of both lines by R5020 but n...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF01806133
更新日期:1987-10-01 00:00:00
abstract::The association between body fat distribution and breast cancer risk was studied in 5923 pre- and 3568 post-menopausal women, participating in a breast cancer screening project (the DOM-project in Utrecht, the Netherlands). Cases were fifty six premenopausal women and thirty eight postmenopausal women with breast canc...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF00666491
更新日期:1995-04-01 00:00:00
abstract::Elevated body weight is a risk factor for postmenopausal breast cancer and is associated with increased incidence of spontaneous and chemically induced mammary tumors (MTs) in rodents. In this study, genetically obese Lep(ob)Lep(ob) female mice that overexpress human TGF-alpha (transforming growth factor-alpha) were u...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1021891825399
更新日期:2003-02-01 00:00:00
abstract:PURPOSE:To estimate the performance of diffusion-weighted imaging (DWI) for breast cancer detection. METHODS:Consecutive breast magnetic resonance imaging examinations performed from January to September 2016 were retrospectively evaluated. Examinations performed before/after neoadjuvant therapy, lacking DWI sequences...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-019-05519-y
更新日期:2020-02-01 00:00:00