Breast cancer is one of the leading causes of cancer-related deaths in women. Regardless of prognosis, all women with breast cancer are at risk for early recurrence. Nearly 50% of early recurrences occur within 5 years of surgery, and they peak at 2 years after surgery in women treated with ...

Resistance to the antiestrogen tamoxifen remains a major problem in the management of estrogen receptor-positive breast cancer. Knowledge on the resistance mechanisms is needed to develop more effective therapies. Breast cancer antiestrogen resistance 4 (BCAR4) was identified in a functional screen for genes involved in tamoxifen resistance. BCAR4is expressed in ...

Endocrine therapy for breast cancer may affect cognition. The purpose of this study was to examine whether cognitive function improves after cessation of adjuvant endocrine therapy. Change in cognitive function was assessed in 100 postmenopausal breast cancer patients in the BIG 1-98 trial, who were randomized to receive 5 years ...

Tamoxifen is widely used for the treatment of breast cancer. Pterostilbene, a bioavailable stilbenoid found in blueberries, has been found to inhibit breast cancer growth in vitro. It was hypothesized that combining pterostilbene with tamoxifen would produce additive effects on estrogen receptor-positive breast cancer cells. Two estrogen receptor-positive breast cancer ...

Anastrozole is a third-generation aromatase inhibitor used in the adjuvant setting for the treatment of hormone receptor-positive breast cancer. Several adjuvant randomized trials have reported greater efficacy for anastrozole when compared to tamoxifen. This review discusses the mechanism of action of anastrozole; pharmacokinetic and pharmacodynamic characteristics; results of randomized controlled ...

Treatment with tamoxifen (TAM) increases the risk of developing endometrial cancer in women. The carcinogenic effect is thought to involve initiation and/or promotion resulting from DNA damage induced by TAM as well as its estrogenic action. To minimize this serious side-effect while increasing the anti-breast cancer potential, a new benzopyran ...

ABSTRACT: INTRODUCTION: Basic research has indicated that tocotrienols have potent antiproliferative and proapoptotic effects that would be expected to reduce the effect of breast cancer. METHODS: We conducted a double-blinded, placebo-controlled pilot trial to test the effectiveness of adjuvant tocotrienol therapy in combination with tamoxifen for 5 years in women ...

Variant alleles of the CYP2C19 gene were recently associated with survival in breast cancer patients on tamoxifen therapy. CYP2C19 is one of the enzymes involved in the metabolism of tamoxifen into active metabolites. We investigated the hypothesis that CYP2C19*2 and *3 variants, known for their lack of enzyme activity, are ...

Long-term treatment with tamoxifen (TAM) increases the risk of developing endometrial cancer in women. Several antiestrogens developed in last decades have been discontinued from clinical testing because of their undesirable effects on the uterus. To avoid such serious side-effect while increasing the drug's anti-breast cancer potential, new triphenylethylene antiestrogens, 2E-3-{4-[(E)-4-chloro-1-(4-hydroxyphenyl)-2-phenylbut-1-enyl]-phenyl} ...

The Breast International Group (BIG) 1-98 and Arimidex, Tamoxifen Alone or in Combination (ATAC) trials demonstrated that, in postmenopausal women with hormone receptor positive (HR+) early-stage breast cancer, 5 years of initial adjuvant endocrine therapy with letrozole or anastrozole is superior to tamoxifen. With expected generic availability of anastrozole in ...

Juvenile breast hypertrophy is uncommon and is characterized by excessive breast enlargement in the peripubertal period. The clinical entity is thought to result from increased sensitivity of mammary tissue to normal levels of circulating hormones. Here, we report a female patient, aged 12 years and 6 months, suffering from juvenile ...

Pregnancy occurring after multimodal therapy in a woman with breast cancer with a 1-year follow-up period is a relatively rare condition and has been defined as pregnancy-associated breast cancer. A patient can become pregnant after chemotherapy for breast cancer while she is on tamoxifen. However, the effects of tamoxifen on ...

Breast cancer anti-oestrogen resistance 4 (BCAR4) was identified in a search for genes involved in anti-oestrogen resistance in breast cancer. We explored whether BCAR4 is predictive for tamoxifen resistance and prognostic for tumour aggressiveness, and studied its function. BCAR4 mRNA levels were measured in primary breast tumours, and evaluated for ...

Concurrent use of tamoxifen and cytochrome P450 2D6 (CYP2D6) inhibitors, such as selective serotonin reuptake inhibitors, has been shown to decrease plasma concentrations of tamoxifen metabolites. However, it is still unclear whether such concurrent use affects tamoxifen's effectiveness. Thus, the objective of this study is to determine whether concurrent use ...

The association between CYP2D6 genotype and outcome in breast cancer patients treated with adjuvant tamoxifen remains controversial. We assessed the influence of comprehensive versus limited CYP2D6 genotype in the context of tamoxifen adherence and co-medication in a large cohort of 618 patients. Genotyping of 33 CYP2D6 alleles used two archival ...

There is substantial evidence that circulating estrogens promote the proliferation of breast cancer. Consequently, adjuvant hormonal treatment strategies targeting estrogen action have been established. Such hormonal therapies include selective estrogen receptor modulators, such as tamoxifen, which interfere at the estrogen receptors directly, or non-steroidal aromatase inhibitors, such as anastrozole and ...

Estrogen receptor (ER) action is modulated by posttranslational modifications. Although ERalpha phosphorylation correlates with patient outcome, ERbeta is similarly phosphorylated but its significance in breast cancer has not been addressed. We investigated whether ERbeta that is phosphorylated at serine 105 (S105-ERbeta) is expressed in breast cancer and assessed potential clinical ...

We hypothesize that measurement of gene expression related to estrogen receptor α (ER; gene name ESR1) within a breast cancer sample represents intrinsic tumoral sensitivity to adjuvant endocrine therapy. A genomic index for sensitivity to endocrine therapy (SET) index was defined from genes coexpressed with ESR1 in 437 microarray profiles ...

Endocrine therapy in the setting of breast cancer has undoubtedly advanced clinical outcomes in this disease, but treatment with endocrine therapy is accompanied by a wide spectrum of side effects. It is of prime importance to understand and characterize these toxicities to facilitate clinical decision-making. Somewhat surprisingly, there is a ...

Vascular endothelial growth factor A (VEGF-A) and vascular endothelial growth factor receptor 2 (VEGFR2) are the key factors mediating neo-vascularization. They are often coexpressed in breast cancer. Sex steroids may stimulate angiogenesis via the estrogen receptor (ER) pathway. We investigated to compare the effects of the addition of tamoxifen to ...

PURPOSE: To develop evidence-based guidelines, based on a systematic review, for endocrine therapy for postmenopausal women with hormone receptor-positive breast cancer. METHODS: A literature search identified relevant randomized trials. Databases searched included MEDLINE, PREMEDLINE, the Cochrane Collaboration Library, and those for the Annual Meetings of the American Society of Clinical ...

Endocrine therapy is the main therapeutic option for patients with estrogen receptor (ERalpha)-positive breast cancer. Resistance to this treatment is often associated with estrogen-independent activation of ERalpha. In this study, we show that in ERalpha-positive breast cancer cells, activation of the receptor tyrosine kinase RET (REarranged during Transfection) by its ...

Clinical trials conducted in Western countries have shown that aromatase inhibitors are associated with better disease-free survival (DFS) than tamoxifen in postmenopausal early breast cancer. Because pharmacogenetic differences in drug-metabolizing genes may cause ethnic differences, assessment of the efficacy and tolerability of aromatase inhibitors in non-white women is warranted. This ...

OBJECTIVE: This study aimed to evaluate the cost-effectiveness of postoperative adjuvant tamoxifen therapy using data from a Korean breast cancer registry. METHODS: In this retrospective, observational cohort study, patients were selected from the Korean Breast Cancer Society database. Women with stage I, II, or III breast cancer (diagnosed between 1981 ...

Antiestrogen therapies generally offer significant disease control to hormone receptor-positive recurrent or metastatic breast cancer patients and are substantially better tolerated than standard chemotherapy regimens, thus representing an attractive first treatment option. The steroidal aromatase inhibitor (AI) exemestane exhibits antitumor effects by lowering full-body estrogen production in postmenopausal women and ...

Raloxifene was approved in 2007 by the FDA for the chemoprevention of breast cancer in postmenopausal women at high risk for invasive breast cancer. Approval was based in part on the improved safety profile for raloxifene relative to the standard treatment of tamoxifen. However, recent studies have demonstrated the ability ...

Adjuvant endocrine treatment is an essential component in therapy for hormone receptor-positive breast cancer. Among postmenopausal patients, options include tamoxifen, aromatase inhibitors, or a sequence of these agents. Tamoxifen and aromatase inhibitors have distinctive side-effect profiles. Among premenopausal women, tamoxifen remains the standard treatment. The role of ovarian suppression in ...

Angiogenin, a 14.2-kDa polypeptide member of the RNase A superfamily, has potent angiogenic effects. Nuclear accumulation of angiogenin is essential for its angiogenic activity. Increased angiogenin expression has been associated with the transition of normal breast tissue into invasive breast carcinoma. In this article, we investigated whether estradiol (E(2)) affected ...

MicroRNAs (miRNAs) are small RNA molecules that modulate gene expression and which have been implicated in cancer. We evaluated whether five candidate predictive miRNAs, derived from a pilot study in which 249 miRNAs were assayed, were associated with clinical benefit of tamoxifen therapy in advanced breast cancer. These five miRNAs ...

Evidence has emerged that the clinical benefit of tamoxifen is related to the functional status of the hepatic metabolizing enzyme cytochrome P450 2D6 (CYP2D6). CYP2D6 is the key enzyme responsible for the generation of the potent tamoxifen metabolite, endoxifen. Multiple studies have examined the relationship of CYP2D6 status to breast ...

Aromatase inhibitors (AIs) have largely replaced tamoxifen as adjuvant hormonal therapy for postmenopausal women with early breast cancer. While tamoxifen is effective in reducing breast cancer recurrence and mortality, recent data indicate two peaks of early, mostly distant metastatic recurrences in patients receiving tamoxifen, and AIs have proven more effective ...

Aromatase inhibitors (AIs) have largely replaced tamoxifen as adjuvant hormonal therapy for postmenopausal women with early breast cancer. While tamoxifen is effective in reducing breast cancer recurrence and mortality, recent data indicate two peaks of early, mostly distant metastatic recurrences in patients receiving tamoxifen, and AIs have proven more effective ...

PURPOSE: The use of cytochrome P450 2D6-inhibiting drugs (CYP2D6 inhibitors) during tamoxifen treatment leads to a decrease in plasma concentration of endoxifen, the major active tamoxifen metabolite. Concomitant use of CYP2D6 inhibitors, such as selective serotonin reuptake inhibitors, as well as low tamoxifen adherence may negatively impact tamoxifen efficacy in ...

Cognitive function in postmenopausal women receiving letrozole or tamoxifen as adjuvant endocrine treatment was compared during the fifth year of treatment in a substudy of the BIG 1-98 trial. In BIG 1-98 patients were randomized to receive adjuvant (A) 5-years tamoxifen, (B) 5-years letrozole, (C) 2-years tamoxifen followed by 3-years ...

Tamoxifen, an effective treatment of breast cancer, has been shown to cause ocular toxic effects. The purpose of this study was to determine retinal toxicity by full-field and focal electroretinograms (ERGs) in patients treated with tamoxifen. Fullfield and focal ERGs were obtained from three groups: Tamoxifen-14 females (47-72 years, mean ...

Tamoxifen is currently the standard of care for premenopausal women with hormone receptor-positive early breast cancers. However, endocrine strategies in premenopausal women include not only estrogen receptor blockade with tamoxifen but also temporary suppression of ovarian estrogen synthesis by luteinizing hormone-releasing hormone (LHRH) agonists, or permanent interruption of ovarian estrogen ...

Up to one-quarter of breast cancer patients suffer clinically significant depression in the year after diagnosis, which may respond to intervention. About half may be prescribed a psychotropic medication, such as a selective serotonin reuptake inhibitor (SSRI), while completing breast cancer therapy. Cytochrome P-450 2D6 (CYP2D6) metabolizes SSRIs and also ...

Tamoxifen resistance is one of the overarching challenges in the treatment of patients with estrogen receptor (ER)-positive breast cancer. Through a genome-wide RNA interference screen to discover genes responsible for tamoxifen resistance in vitro, we identified insulin-like growth factor binding protein 5 (IGFBP5) as a determinant of drug sensitivity. Specific ...

PURPOSE: Nuclear receptor coactivator expression and activity may partly explain the complex agonist/antagonist effects of tamoxifen at clinical level. In a preoperative trial, dose reduction from 20 to 1 mg tamoxifen was associated with retained antiproliferative effect on breast cancer. Here, we assessed the gene expression of the steroid receptor ...

Phosphorylation of estrogen receptor α at serine 305 (ERαS305-P) by protein kinase A (PKA) or p21-activated kinase 1 (PAK1) has experimentally been associated with tamoxifen sensitivity. Here, we investigated the clinical application of this knowledge to predict tamoxifen resistance in ER-positive breast cancer patients. Using immunohistochemistry, a score including PAK1 ...

The cell cycle regulating protein p27(Kip1) (p27) has dual roles by acting as both a cdk-inhibitor and as an assembly factor for different cdk-complexes. Loss of p27 has been linked to malignant features in tumours, however the exact role of p27 deregulation in breast cancer regarding prognostic and treatment predictive ...

BACKGROUND: Tamoxifen, a selective estrogen receptor modulator, and fulvestrant, a selective estrogen receptor down-regulator (SERD), are now available for estrogen receptor-positive breast cancer patients. However, these patients acquire drug-resistance during the treatments. We identified a new orally active nonsteroidal SERD, CH4986399, which is structurally unrelated to fulvestrant and tamoxifen. MATERIALS ...

PURPOSE: In vitro, p21-activated kinase 1 (Pak1) phosphorylates the serine 305 residue of the estrogen receptor alpha (ERalpha) and influences the response of breast cancer cells to tamoxifen. We investigated the influence of Pak1 and pERalpha(ser305) on breast cancer prognosis and results of tamoxifen therapy. EXPERIMENTAL DESIGN: We examined Pak1 ...

PURPOSE OF REVIEW: To describe the current status regarding the duration of adjuvant tamoxifen and/or aromatase inhibitors in women with early-stage hormone receptor positive breast cancer. RECENT FINDINGS: Women with early-stage breast cancers that express estrogen and/or progesterone receptors benefit from adjuvant hormonal therapy with antiestrogen drugs. Five years of ...

Tamoxifen reduces primary breast cancer incidence, yet causes serious side effects. To date, few women with increased breast cancer risk have elected to use tamoxifen for chemoprevention. The objective of the study was to determine women's knowledge of and attitudes toward tamoxifen following exposure to a tailored decision aid (DA). ...

Roux-en-Y gastric bypass is a gastric reduction duodenal switch with a combination of restrictive and malabsorptive procedures. It is the most common gastric bypass procedure performed in the United States. Malabsorption causing nutritional deficiencies does occur, yet a PubMed literature search (1955-2009) returned no reports of malabsorption of anticancer agents ...

Tamoxifen can reduce the risk of developing invasive estrogen receptor-positive breast cancer by 49%, but it is unknown how many women in the United States are taking tamoxifen for primary prevention of breast cancer. Data from the years 2000 and 2005 National Health Interview Surveys were analyzed to estimate the ...

The 21-gene OncotypeDX recurrence score (RS) assay quantifies the risk of distant recurrence in tamoxifen-treated patients with node-negative, estrogen receptor (ER)-positive breast cancer. We investigated the association between RS and risk for locoregional recurrence (LRR) in patients with node-negative, ER-positive breast cancer from two National Surgical Adjuvant Breast and Bowel ...

17ss-Hydroxysteroid dehydrogenases (17HSDs) are involved in the local regulation of sex steroids. 17HSD1 converts oestrone (E1) to the more potent oestradiol (E2) and 17HSD2 catalyses the reverse reaction. The aim of this study was to investigate the expression of these enzymes in premenopausal breast cancers and to analyse if they ...

Endoxifen is the key active metabolite of tamoxifen, a widely used breast cancer drug. Orally administered tamoxifen, is extensively metabolized by cytochrome P450 (CYP) enzymes, namely CYP3A4 and CYP2D6, into active metabolites, especially endoxifen. Due to genetic polymorphism of CYP2D6, significant numbers of women metabolize tamoxifen to varying degree and ...