Abstract:
:Metformin may exert anti-cancer effects through indirect (insulin-mediated) or direct (insulin-independent) mechanisms. We report results of a neoadjuvant "window of opportunity" study of metformin in women with operable breast cancer. Newly diagnosed, untreated, non-diabetic breast cancer patients received metformin 500 mg tid after diagnostic core biopsy until definitive surgery. Clinical (weight, symptoms, and quality of life) and blood [fasting serum insulin, glucose, homeostasis model assessment (HOMA), C-reactive protein (CRP), and leptin] attributes were compared pre- and post-metformin as were terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and Ki67 scores (our primary endpoint) in tumor tissue. Thirty-nine patients completed the study. Mean age was 51 years, and metformin was administered for a median of 18 days (range 13-40) up to the evening prior to surgery. 51 % had T1 cancers, 38 % had positive nodes, 85 % had ER and/or PgR positive tumors, and 13 % had HER2 overexpressing or amplified tumors. Mild, self-limiting nausea, diarrhea, anorexia, and abdominal bloating were present in 50, 50, 41, and 32 % of patients, respectively, but no significant decreases were seen on the EORTC30-QLQ function scales. Body mass index (BMI) (-0.5 kg/m(2), p < 0.0001), weight (-1.2 kg, p < 0.0001), and HOMA (-0.21, p = 0.047) decreased significantly while non-significant decreases were seen in insulin (-4.7 pmol/L, p = 0.07), leptin (-1.3 ng/mL, p = 0.15) and CRP (-0.2 mg/L, p = 0.35). Ki67 staining in invasive tumor tissue decreased (from 36.5 to 33.5 %, p = 0.016) and TUNEL staining increased (from 0.56 to 1.05, p = 0.004). Short-term preoperative metformin was well tolerated and resulted in clinical and cellular changes consistent with beneficial anti-cancer effects; evaluation of the clinical relevance of these findings in adequately powered clinical trials using clinical endpoints such as survival is needed.
journal_name
Breast Cancer Res Treatjournal_title
Breast cancer research and treatmentauthors
Niraula S,Dowling RJ,Ennis M,Chang MC,Done SJ,Hood N,Escallon J,Leong WL,McCready DR,Reedijk M,Stambolic V,Goodwin PJdoi
10.1007/s10549-012-2223-1subject
Has Abstractpub_date
2012-10-01 00:00:00pages
821-30issue
3eissn
0167-6806issn
1573-7217journal_volume
135pub_type
临床试验,杂志文章abstract::Afatinib is an oral, ErbB family blocker, which covalently binds and irreversibly blocks all kinase-competent ErbB family members. This phase II, open-label, single-arm study explored afatinib activity in human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients progressing after trastuzumab trea...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,多中心研究
doi:10.1007/s10549-012-2003-y
更新日期:2012-06-01 00:00:00
abstract:PURPOSE:Fulvestrant is a selective estrogen receptor downregulator (SERD) that is approved for first- or second-line use as a single agent or in combination with cyclin dependent kinase or phosphatidylinositol 3-kinase inhibitors for the treatment of metastatic breast cancer. Fulvestrant exhibits exceptionally effectiv...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-019-05454-y
更新日期:2020-01-01 00:00:00
abstract::The complexity of breast cancer biology makes it challenging to analyze large datasets of clinicopathologic and molecular attributes, toward identifying the key prognostic features and producing systems capable of predicting which patients are likely to relapse. We applied machine-learning techniques to analyze a set ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-009-0557-0
更新日期:2010-06-01 00:00:00
abstract:PURPOSE:Mitochondrial unfolding protein are abundant in breast cancer cells, but the mechanism by which breast cancer cells resist apoptosis is still not fully elucidated. In this study, we explored the role of mitochondrial unfolded protein response (mtUPR)-related proteins in four types of breast cancer tissues. MET...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-020-05729-9
更新日期:2020-08-01 00:00:00
abstract::We aimed to compare the clinicopathological features, treatment strategies and clinical outcomes of breast sarcomas (BS) and malignant phyllodes tumours (MPT), and determine their prognostic factors. Cases of BS and MPT diagnosed at the Department of Pathology, Singapore General Hospital from January 1991 to December ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-016-3946-1
更新日期:2016-09-01 00:00:00
abstract::Since germline mutations in the PALB2 (Partner and Localizer of BRCA2) gene have been identified as breast cancer (BC) susceptibility alleles, the geographical spread and risks associated with PALB2 mutations are subject of intense investigation. Patients with bilateral breast cancer constitute a valuable group for ge...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-010-1290-4
更新日期:2011-04-01 00:00:00
abstract:BACKGROUND:The genes mutated in the cancer-prone syndrome, xeroderma pigmentosum (XP genes), have been well studied both biochemically and mechanistically. These genes are important components of the DNA nucleotide excision repair (NER) pathway, which protects against environmentally-induced cancers. XP genes are also ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-006-9263-3
更新日期:2007-01-01 00:00:00
abstract::Chromosomal instability is a known hallmark of many cancers. DNA polymerases represent a group of enzymes that are involved in the mechanism of chromosomal instability as they have a central function in DNA metabolism. We hypothesized that genetic variation in the polymerase genes may affect gene expression or protein...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-011-1460-z
更新日期:2011-08-01 00:00:00
abstract::The rate of contralateral prophylactic mastectomy (CPM) is rising rapidly, despite limited evidence about the procedure's relative benefits and harms. The objective of this study is to examine the impact of CPM on life expectancy (LE) and quality-adjusted life expectancy (QALE) in women with sporadic unilateral breast...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-015-3462-8
更新日期:2015-07-01 00:00:00
abstract::We characterized the structure and the function of insulin receptors isolated from 10 human breast cancer specimens. We observed that the insulin receptor content, as determined by a specific radioimmunoassay, was four fold increased in human breast cancer tissue when compared to normal breast tissues. In both cancer ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF00662403
更新日期:1993-01-01 00:00:00
abstract::Discomfort during sexual activity is common after breast cancer. Vaginal estrogens are effective but commonly avoided due to systemic absorption. Despite the large commercial market for vaginal lubricants, no randomized studies have compared products. We aimed to compare efficacy and acceptability of two major types o...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,随机对照试验
doi:10.1007/s10549-016-3865-1
更新日期:2016-07-01 00:00:00
abstract::The response to primary chemotherapy is an important prognostic factor in patients with non metastatic breast cancer. In this study we compared the assessment of response performed by clinical palpation to that performed by echography and mammography in 141 out of 157 consecutive breast cancer patients (T2-4, N0-1, M0...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1012277325168
更新日期:2001-09-01 00:00:00
abstract:BACKGROUND:Three tools are currently available to predict the risk of contralateral breast cancer (CBC). We aimed to compare the performance of the Manchester formula, CBCrisk, and PredictCBC in patients with invasive breast cancer (BC). METHODS:We analyzed data of 132,756 patients (4682 CBC) from 20 international stu...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-020-05611-8
更新日期:2020-06-01 00:00:00
abstract::One of the most efficacious primary therapies in HER2-positive breast cancer was published by the M.D. Anderson group in 2005. This randomized trial evaluated the addition of trastuzumab to a taxane-anthracycline based chemotherapy. Despite largely significant differences in pathological complete response (pCR) in the...
journal_title:Breast cancer research and treatment
pub_type: 临床试验,杂志文章
doi:10.1007/s10549-012-2149-7
更新日期:2012-08-01 00:00:00
abstract:PURPOSE:The safety of immediate breast reconstruction (IBR) in older women is largely unknown. This study aimed to determine the 30-day postoperative complication rates following IBR (implant-based or autologous) in older women (≥ 70 years) with breast cancer and to compare them to younger women (18-69 years). METHODS...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-019-05273-1
更新日期:2019-08-01 00:00:00
abstract::Breast cancer (BC) is a common disease that generally occurs in women over the age of 50, and the risk is especially high for women over 60 years of age. One of the major BC therapeutic problems is that tumors initially responsive to chemotherapeutic approaches can progress to more aggressive forms poorly responsive t...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,评审
doi:10.1007/s10549-014-3156-7
更新日期:2014-11-01 00:00:00
abstract:PURPOSE:miRNAs have been linked to chemosensitivity of breast cancer cells in vitro. In patients, however, there is no clinically validated method for predicting chemotherapy response. The aim of this study was to assess whether (I) a specific pattern of miRNA expression in pretherapeutic biopsies can predict response ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-017-4132-9
更新日期:2017-04-01 00:00:00
abstract::Psoriasin (S100A7) is a calcium-binding protein that has shown to be highly expressed in high-grade ductal carcinoma in situ (DCIS) and a subset of invasive breast cancers. However, its role in invasion and metastasis is not very well known. In this study, we have shown that S100A7 differentially regulates epidermal g...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-013-2491-4
更新日期:2013-04-01 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::Kinase suppressor of Ras 1 (KSR1) has been implicated in tumorigenesis in multiple cancers, including skin, pancreatic and lung carcinomas. However, our recent study revealed a role of KSR1 as a tumour suppressor in breast cancer, the expression of which is potentially correlated with chemotherapy response. Here, we a...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-015-3443-y
更新日期:2015-06-01 00:00:00
abstract::Aromatase inhibitors (AIs) are used for treatment of estrogen receptor α (ER)-positive breast cancer; however, resistance is a major obstacle for optimal outcome. This preclinical study aimed at identifying potential new treatment targets in AI-resistant breast cancer cells. Parental MCF-7 breast cancer cells and four...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-015-3284-8
更新日期:2015-02-01 00:00:00
abstract::Metastatic breast cancer is a systemic disease. However, certain subsets of patients, such as those with oligometastatic breast cancer (OMBC), have long-term survival prospects. Our aim was to evaluate the clinical relevance of OMBC in pulmonary metastasectomy of recurrent breast cancer. We also investigated lung meta...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-014-3111-7
更新日期:2014-09-01 00:00:00
abstract:PURPOSE:Time to surgery (TTS) is a potentially modifiable factor associated with survival after breast cancer diagnosis and can serve as a proxy for quality of oncologic care coordination. We sought to determine whether factors associated with delays in TTS vary between patients who receive neoadjuvant systemic therapy...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-020-06012-7
更新日期:2020-11-18 00:00:00
abstract:PURPOSE:Neutropenia is the most common toxicity of CDK4/6 inhibitors, causing frequent dose interruptions. However, CDK4/6 inhibitor-induced neutropenia shows a benign clinical course in contrast to that caused by chemotherapy. Here, we investigated the safety of a new dose scheme for palbociclib, which avoids dose del...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-020-05750-y
更新日期:2020-08-01 00:00:00
abstract::The high potency and selectivity of new aromatase inhibitors has translated to greater efficacy and improved tolerability in comparison with established second-line hormonal agents for advanced breast cancer in phase III clinical trials. Two pharmacological studies are reported which assess the use of one of these inh...
journal_title:Breast cancer research and treatment
pub_type: 临床试验,杂志文章
doi:10.1023/a:1006289811540
更新日期:1999-07-01 00:00:00
abstract::Metastasizing cancer cells can invade the extracellular matrix using plasma membrane protrusions, termed invadopodia, that contact and dissolve the matrix. Various membrane associated proteases localized on the invadopodial membranes are responsible for the extracellular matrix degradation. Work from our laboratory sh...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,评审
doi:10.1007/BF00666155
更新日期:1994-01-01 00:00:00
abstract::The aim of this study was to evaluate the difference in outcomes based on p53 overexpression of patients with breast cancer who received adjuvant therapy following local treatment for invasive ductal carcinoma, not otherwise specified. We analyzed data from 4,683 patients with cancer enrolled in two institutions betwe...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,多中心研究
doi:10.1007/s10549-009-0560-5
更新日期:2010-06-01 00:00:00
abstract:PURPOSE:Studies of the etiology of inflammatory breast cancer (IBC), a rare but aggressive breast cancer, have been hampered by limited risk factor information. We extend previous studies by evaluating a broader range of risk factors. METHODS:Between 2009 and 2015, we conducted a case-control study of IBC at six cente...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-020-05864-3
更新日期:2020-11-01 00:00:00
abstract::We conducted gene-based analysis in 26 genes in the FGFR signaling pathway to identify genes carrying genetic variation affecting risk of breast cancer and the specific estrogen receptor (ER) subtypes. Tagging single-nucleotide polymorphisms (SNPs) for each gene were selected and genotyped on a customized Illumina Exo...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-015-3672-0
更新日期:2016-01-01 00:00:00
abstract::Tumor formation can result from a decrease in cell death, as well as an increase in cell proliferation. In spite of the high incidence of mammary gland tumors (MGTs) in female dogs, the understanding of its etiology is still poor. Consistent with several proto-oncogenes (such as Wnt) for the mammary gland, sFRP2 is ex...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-006-9233-9
更新日期:2006-11-01 00:00:00