Abstract:
:The mechanisms by which breast cancer (BrC) can successfully metastasize are complex and not yet fully understood. Our goal was to identify tumor-induced stromal changes that influence metastatic cell behavior, and may serve as better targets for therapy. To identify stromal changes in cancer-bearing tissue, dual-species gene expression analysis was performed for three different metastatic BrC xenograft models. Results were confirmed by immunohistochemistry, flow cytometry, and protein knockdown. These results were validated in human clinical samples at the mRNA and protein level by retrospective analysis of cohorts of human BrC specimens. In pre-clinical models of BrC, systemic recruitment of S100A8+ myeloid cells-including myeloid-derived suppressor cells (MDSCs)-was promoted by tumor-derived factors. Recruitment of S100A8+ myeloid cells was diminished by inhibition of tumor-derived factors or depletion of MDSCs, resulting in fewer metastases and smaller primary tumors. Importantly, these MDSCs retain their ability to suppress T cell proliferation upon co-culture. Secretion of macrophage inhibitory factor (MIF) activated the recruitment of S100A8+ myeloid cells systemically. Inhibition of MIF, or depletion of MDSCs resulted in delayed tumor growth and lower metastatic burden. In human BrC specimens, increased mRNA and protein levels of S100A8+ infiltrating cells are highly associated with poor overall survival and shorter metastasis free survival of BrC patients, respectively. Furthermore, analysis of nine different human gene expression datasets confirms the association of increased levels of S100A8 transcripts with an increased risk of death. Recruitment of S100A8+ myeloid cells to primary tumors and secondary sites in xenograft models of BrC enhances cancer progression independent of their suppressive activity on T cells. In clinical samples, infiltrating S100A8+ cells are associated with poor overall survival. Targeting these molecules or associated pathways in cells of the tumor microenvironment may translate into novel therapeutic interventions and benefit patient outcome.
journal_name
Breast Cancer Res Treatjournal_title
Breast cancer research and treatmentauthors
Drews-Elger K,Iorns E,Dias A,Miller P,Ward TM,Dean S,Clarke J,Campion-Flora A,Rodrigues DN,Reis-Filho JS,Rae JM,Thomas D,Berry D,El-Ashry D,Lippman MEdoi
10.1007/s10549-014-3122-4subject
Has Abstractpub_date
2014-11-01 00:00:00pages
41-59issue
1eissn
0167-6806issn
1573-7217journal_volume
148pub_type
杂志文章abstract::The purpose of this study was to examine the urban-rural difference in breast cancer mortality between 2002 and 2008 in China. A longitudinal analysis of mortality data was performed. Mortality data were extracted from Chinese Health Statistics Yearbook. Linear regression was used to examine the statistical significan...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-010-1276-2
更新日期:2011-02-01 00:00:00
abstract:BACKGROUND:The objective was to determine the additional value of pathologic examination using three-level sectioning and immunocytokeratin (ICK) staining of sentinel lymph node (SN) biopsies in cT1-2N0M0 breast carcinoma patients regarding lymph node staging and eligibility of systemic therapy taking primary tumor cha...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-006-9434-2
更新日期:2007-09-01 00:00:00
abstract:PURPOSE:When combined with anthracyclines, the humanized anti-HER2 monoclonal antibody trastuzumab (Herceptin) provides significant clinical benefit for women with HER2-overexpressing metastatic breast cancer. However, its use is limited by severe cardiotoxicity. To clarify whether myocardial HER2 and HER4 expression i...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/b:brea.0000003916.39959.73
更新日期:2003-11-01 00:00:00
abstract:PURPOSE:To update and expand on data related to treatment, resource utilization, and costs by cancer stage in Canadian patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC). METHODS:We analyzed data for adult women diagnosed with invasive HR+/HER2- B...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-020-05960-4
更新日期:2020-10-16 00:00:00
abstract:BACKGROUND:Paget's disease of the breast is an uncommon presentation of breast malignancy, accounting for 1-3% of all the breast tumors and presents in different histopathologic patterns: in association with an underlying invasive or non invasive carcinoma, or without any underlying neoplasia. In the literature, differ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-007-9880-5
更新日期:2008-12-01 00:00:00
abstract::The effects of pituitary adenylate cyclase activating polypeptide (PACAP) analogs were investigated using breast cancer cells. 125I-PACAP-27 bound with high affinity (Kd = 5 nM) to T47D cells (Bmax = 29,000 per cell). Specific 125I-PACAP-27 binding was inhibited half maximally by PACAP-27, PACAP-38, PACAP(6-38) and PA...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1006262611290
更新日期:1999-07-01 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::To reduce the risk of adjustment problems for breast cancer patients in mainland China, we examined the efficacy of a multidiscipline mentor-based program, Be Resilient to Breast Cancer (BRBC), delivered after breast surgery to (a) increase protective factors of social support, hope for the future, etc.; (b) decrease ...
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/s10549-016-3881-1
更新日期:2016-08-01 00:00:00
abstract::A review of the literature finds that women diagnosed with breast cancer, who were on an aspirin regimen, experienced a decreased risk of distant metastases and death. Several recent studies have reported an improvement in overall survival in colorectal cancer patients who harbored mutations in the oncogene PIK3CA and...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-016-3729-8
更新日期:2016-02-01 00:00:00
abstract::Seroma formation after axillary lymphadenectomy in women with breast cancer remains a problem despite many efforts to reduce surgery-related morbidity. In a prospective, randomised, open, parallel-group, controlled clinical trial we evaluated the effect of a fibrin-glue coated collagen patch (TachoComb H, Nycomed Phar...
journal_title:Breast cancer research and treatment
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1023/a:1010671209279
更新日期:2001-05-01 00:00:00
abstract:BACKGROUND:The estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) statuses are frequently discordant between the primary tumor and metastatic lesions in metastatic breast cancer. This can have important therapeutic implications. PATIENTS AND METHODS:In all, 541 pati...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-020-05746-8
更新日期:2020-08-01 00:00:00
abstract::Axillary management in breast cancer is becoming increasingly conservative. This approach is based on the identification of low axillary burden on sentinel node biopsy (SNB). The modern practice of routine pre-operative axillary ultrasound has meant that patients are 'fast tracked' to axillary node clearance (ANC) in ...
journal_title:Breast cancer research and treatment
pub_type: 社论
doi:10.1007/s10549-017-4313-6
更新日期:2017-09-01 00:00:00
abstract:INTRODUCTION:Since older patients with breast cancer are underrepresented in clinical trials, an oncogeriatric approach is advocated to guide treatment decisions. However, the effect on outcomes is unclear. The aim of this study was to compare treatments and outcomes between patients treated in an oncogeriatric and a s...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-020-05860-7
更新日期:2020-11-01 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::The glycolytic phenotype is a widespread phenomenon in solid cancer forms, including breast cancer. Dichloroacetate (DCA) has recently been proposed as a novel and relatively non-toxic anti-cancer agent that can reverse the glycolytic phenotype in cancer cells through the inhibition of pyruvate dehydrogenase kinase. W...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-009-0435-9
更新日期:2010-02-01 00:00:00
abstract::The expression of amphiregulin (AR), heregulin (HRG), and cripto-1 (CR-1) mRNA transcripts was assessed in 60 human primary breast carcinoma. AR and HRG transcripts were expressed respectively in 58% and 25% of the carcinomas as measured by Northern blot analysis. CR-1 mRNA was found in 77% of the carcinomas using Rev...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF00665981
更新日期:1995-09-01 00:00:00
abstract::In 1973, McGuire and Chamness (In: O'Malley BW and Means AR (ed) Receptors for Reproductive Hormones, Plenum Press) summarized their work on the estrogen receptor in animal and human breast tumors, and in so doing described a target for therapeutic intervention. At that time there were no clinically useful antiestroge...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,评审
doi:10.1007/BF00713399
更新日期:1995-01-01 00:00:00
abstract:PURPOSE:Preoperative paravertebral blocks (PPVBs) are routinely used for treating post-mastectomy pain, yet uncertainties remain about the cost-effectiveness of this modality. We aim to evaluate the cost-effectiveness of PPVBs at common willingness-to-pay (WTP) thresholds. METHODS:A decision analytic model compared tw...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,评审
doi:10.1007/s10549-017-4371-9
更新日期:2017-10-01 00:00:00
abstract::A novel human mammary epithelial cell line, HME348, was established from benign breast tissue from a 44-year-old germ-line BRCA2 mutation carrier with a history of stage 1 breast cancer. Mutation analysis showed that the patient had a known 6872del4 BRCA2 heterozygous mutation. The human mammary epithelial cells passa...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-006-9189-9
更新日期:2006-09-01 00:00:00
abstract:PURPOSE:Little is known about different ways of assessing risk of distant recurrence following cancer treatment (e.g., numeric or descriptive). We sought to evaluate the association between overestimation of risk of distant recurrence of breast cancer and key patient-reported outcomes, including quality of life and wor...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-016-4082-7
更新日期:2017-02-01 00:00:00
abstract::A model for a more precise prognosis of the risk of relapse is needed to avoid overtreatment of lymph node-negative breast cancer patients. A large derivation data set (n = 684) was generated by pooling three independent breast cancer expression microarray data sets. Two major prognostic factors, proliferation and imm...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-011-1626-8
更新日期:2012-04-01 00:00:00
abstract::Taxanes are being used for the treatment of breast cancer. However, cancer cells frequently develop resistance to these drugs with the subsequent recurrence of the tumor. MDA-MB-231 and T-47D breast cancer cell lines were used to assess the effect of paclitaxel treatment on apoptosis and cell cycle, the possible mecha...
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
abstract:BACKGROUND:We report a novel BRCA1 LGR, involving the complete duplication of exon 3, in an Italian patient with a strong family history of breast and ovarian cancer. Our purpose is to provide an effective characterization of this LGR using a combination of different methods able to establish the exact breakpoints of t...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-017-4275-8
更新日期:2017-07-01 00:00:00
abstract::Screening of a breast cancer cDNA library from SKBR3 human breast cancer cells by SEREX (serological analysis of cDNA expression library) using a preselected serum from a breast cancer patient revealed 13 genes, two of which, INT-MI-1 and INT-MI-2, encode novel gene products, while the remaining 11 genes and their pro...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1015854415746
更新日期:2002-06-01 00:00:00
abstract::Adjuvant therapy for hormone receptor (HR) positive postmenopausal breast cancer patients includes aromatase inhibitors (AI). While both the non-steroidal AI letrozole and the steroidal AI exemestane decrease serum estrogen concentrations, there is evidence that exemestane may be less detrimental to bone. We hypothesi...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-015-3608-8
更新日期:2015-11-01 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:PURPOSE:The stage-specific survival of young breast cancer patients has improved, likely due to diagnostic and treatment advances. We addressed whether survival improvements have reached all socioeconomic groups in a country with universal health care and national treatment guidelines. METHODS:Using Norwegian registry...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-020-05698-z
更新日期:2020-07-01 00:00:00
abstract:PURPOSE:It has been suggested that type 2 diabetes may affect breast cancer prognosis, possibly due to increased diabetes-related comorbidity, or direct effects of insulin resistance and/or hyperinsulinemia. The purpose of this study was to examine the impact of diabetes on survival following breast cancer. METHODS:Us...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-007-9654-0
更新日期:2008-05-01 00:00:00
abstract::Clinical evidence indicates that higher levels of estrogen receptor beta (ERbeta) predicts improved disease-free and overall survival in patients treated with adjuvant tamoxifen therapy. To better understand the mechanisms in which ERbeta can modulate breast cancer therapies, we introduced ERbeta under an inducible pr...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-007-9640-6
更新日期:2008-05-01 00:00:00
abstract::The clinical and pathological heterogeneity of breast cancer has instigated efforts to stratify breast cancer sub-types according to molecular profiles. These profiling efforts are now being augmented by large-scale functional screening of breast tumour cell lines, using approaches such as RNA interference. We have de...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-010-0945-5
更新日期:2010-11-01 00:00:00