Abstract:
PURPOSE:A number of studies have tested the hypothesis that breast cancer patients with low-activity CYP2D6 genotypes achieve inferior benefit from tamoxifen treatment, putatively due to lack of metabolic activation to endoxifen. Studies have provided conflicting data, and meta-analyses suggest a small but significant increase in cancer recurrence, necessitating additional studies to allow for accurate effect assessment. We conducted a retrospective pharmacogenomic analysis of a prospectively collected community-based cohort of patients with estrogen receptor-positive breast cancer to test for associations between low-activity CYP2D6 genotype and disease outcome in 500 patients treated with adjuvant tamoxifen monotherapy and 500 who did not receive any systemic adjuvant therapy. METHODS:Tumor-derived DNA was genotyped for common, functionally consequential CYP2D6 polymorphisms (*2, *3, *4, *6, *10, *41, and copy number variants) and assigned a CYP2D6 activity score (AS) ranging from none (0) to full (2). Patients with poor metabolizer (AS = 0) phenotype were compared to patients with AS > 0 and in secondary analyses AS was analyzed quantitatively. Clinical outcome of interest was recurrence free survival (RFS) and analyses using long-rank test were adjusted for relevant clinical covariates (nodal status, tumor size, etc.). RESULTS:CYP2D6 AS was not associated with RFS in tamoxifen treated patients in univariate analyses (p > 0.2). In adjusted analyses, increasing AS was associated with inferior RFS (Hazard ratio 1.43, 95% confidence interval 1.00-2.04, p = 0.05). In patients that did not receive tamoxifen treatment, increasing CYP2D6 AS, and AS > 0, were associated with superior RFS (each p = 0.0015). CONCLUSIONS:This population-based study does not support the hypothesis that patients with diminished CYP2D6 activity achieve inferior tamoxifen benefit. These contradictory findings suggest that the association between CYP2D6 genotype and tamoxifen treatment efficacy is null or near null, and unlikely to be useful in clinical practice.
journal_name
Breast Cancer Res Treatjournal_title
Breast cancer research and treatmentauthors
Hertz DL,Kidwell KM,Hilsenbeck SG,Oesterreich S,Osborne CK,Philips S,Chenault C,Hartmaier RJ,Skaar TC,Sikora MJ,Rae JMdoi
10.1007/s10549-017-4400-8subject
Has Abstractpub_date
2017-11-01 00:00:00pages
277-287issue
1eissn
0167-6806issn
1573-7217pii
10.1007/s10549-017-4400-8journal_volume
166pub_type
杂志文章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::Elevated levels of circulating estrogens and androgens are linked to higher breast cancer risk among postmenopausal women; however, little is known about hormone levels within the breast. Hormone concentrations within the breast may not be reflected in the blood and are likely important contributors to breast carcinog...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-011-1734-5
更新日期:2012-01-01 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
abstract:PURPOSE:To measure peptide concentrations and mRNA expression of the IGF Family in breast cancer and to examine their associations with the disease features. EXPERIMENTAL DESIGN:Fresh tumor samples were collected from 348 patients who underwent surgery for breast cancer. Tissue levels of mRNA and peptide of IGF-I, IGF...
journal_title:Breast cancer research and treatment
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doi:10.1007/s10549-008-0046-x
更新日期:2009-05-01 00:00:00
abstract::Angiogenesis is important for the growth and spread of malignant tumors, and anti-angiogenesis treatment is currently being evaluated for breast cancer and other tumors. Although microvessel density is the most commonly used tissue-based marker of tumor associated angiogenesis, it has significant limitations and has n...
journal_title:Breast cancer research and treatment
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doi:10.1007/s10549-011-1785-7
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-010-1313-1
更新日期:2011-07-01 00:00:00
abstract::A human estrogen receptor (ER) cDNA probe was used to examine genomic DNA extracted from 59 primary invasive breast cancers. The tumors were also studied histopathologically, and their ER status was assessed by hormone-binding assay and immunohistochemical analysis. Southern blots of genomic DNA samples digested with ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF01805976
更新日期:1989-10-01 00:00:00
abstract::IBEP-2, an established cell line recently derived from breast carcinoma, was characterized with regard to estrogen receptor (ER) expression, cell mitogenic response to estrogenic stimulation and sensitivity to antiestrogens. In addition, we examined ER modulation following binding of agonist and antagonists, and the E...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/B:BREA.0000032922.87541.31
更新日期:2004-07-01 00:00:00
abstract::FOXP3-expressing T regulatory lymphocytes (Tregs) have been described as putative mediators of immune tolerance, and thus facilitators of tumor growth. When found in association with various malignancies, Tregs are generally markers of poor clinical outcome. However, it is unknown whether they are also associated with...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-013-2556-4
更新日期:2013-06-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-006-9362-1
更新日期:2007-06-01 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
doi:10.1023/a:1006276120841
更新日期:1999-06-01 00:00:00
abstract::Estrogen receptor alpha (ERalpha) is a well-known target for signaling pathways originating from growth factor receptors. Reactive oxygen species (ROS) can induce activation of extracellular response kinase 1/2 (Erk1/2) and protein kinase B (Akt). Both kinases have been implicated in the phosphorylation of serine 118 ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-008-0221-0
更新日期:2009-11-01 00:00:00
abstract:PURPOSE:Although quality of life (QoL) improves over time for most breast cancer survivors (BCS), BCS may show different patterns of QoL. This study sought to identify distinct QoL trajectories among BCS and to examine characteristics associated with trajectory group membership. METHODS:BCS (N = 653) completed baselin...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-018-4677-2
更新日期:2018-05-01 00:00:00
abstract::Circulating CA 15-3 antigen levels were evaluated in patients with benign diseases and breast cancer patients with no clinical evidence of disease after surgery (NED). Patients with breast cancer NED were followed for tumor recurrence or death during a median of 12.9 months (range 1 to 25 months). CA 15-3 and carcinoe...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF01806524
更新日期:1989-03-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1014815112078
更新日期:2002-03-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-019-05286-w
更新日期:2019-08-01 00:00:00
abstract::Forty-one women with non-metastatic but locally advanced breast cancer were treated by modified radical or radical mastectomy, and were then randomized to receive one of two adjuvant chemotherapy regimens. Regimen A consisted of 6 months of cyclophosphamide, adriamycin, and fluorouracil (CAF) followed by 6 months of c...
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/BF01806692
更新日期:1987-01-01 00:00:00
abstract::The proportional hazards model is frequently used in analyzing the results of clinical trials, when it is often the case that the outcomes are right-censored. This model allows one to measure treatment effects and simultaneously identify and adjust for prognostic factors that might influence the outcome. In this paper...
journal_title:Breast cancer research and treatment
pub_type: 临床试验,杂志文章
doi:10.1007/BF01840837
更新日期:1992-01-01 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::The specific role of dietary fat in breast cancer progression is unclear, although a low-fat diet was associated with decreased recurrence of estrogen receptor alpha negative (ER(-)) breast cancer. ER(-) basal-like MDA-MB-231 and MDA-MB-436 breast cancer cell lines contained a greater number of cytoplasmic lipid dropl...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-009-0594-8
更新日期:2010-08-01 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
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更新日期:2016-08-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章,评审
doi:10.1007/s10549-020-05810-3
更新日期:2020-10-01 00:00:00
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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
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-010-0914-z
更新日期:2011-04-01 00:00:00
abstract::This retrospective study investigates the correlation of intra-individual HER2 status between primary breast cancers and corresponding recurrences in a population derived cohort. The REMARK criteria were used as reference. In 151 breast cancer patients, primary tumors were analyzed for HER2 status on histopathology se...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-010-1029-2
更新日期:2011-01-01 00:00:00
abstract:BACKGROUND:Telomerase is a ribonucleoprotein enzyme that synthesises telomeres in human germ cells, embryogenesis and in cancer, maintaining chromosomal length, stability and cellular immortality. The hTERT gene is the rate-limiting determinant of telomerase reactivation during immortalization and malignant transformat...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-007-9622-8
更新日期:2008-05-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-004-1000-1
更新日期:2005-01-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1006167210269
更新日期:1999-01-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-013-2600-4
更新日期:2013-07-01 00:00:00
abstract::The widespread use of mammography has resulted in the detection of an increasing number of small invasive breast cancers, i.e. those that are 1cm and smaller. Patients with these small cancers generally have a low incidence of axillary lymph node metastases, and this has led some to question the routine use of axillar...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,评审
doi:10.1023/a:1006130911110
更新日期:1998-01-01 00:00:00