Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new arimidex research articles will be listed here shortly after becoming available to us.
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Medical research on arimidex
Review of the ATAC study: tamoxifen versus anastrozole in early-stage breast cancer.
Expert Rev Anticancer Ther. 2008 Dec; 8(12): 1871-81
Needleman SJ, Tobias JS
A 5-year regimen of tamoxifen hormone therapy has historically been the recommendation for hormone receptor-positive, postmenopausal women with early-stage breast cancer. With the advent of aromatase inhibitors, there has been extensive work carried out to investigate the role of these agents in the adjuvant setting. Studies have been designed to answer whether these agents should be used upfront (instead of tamoxifen) or in conjunction (either in a switch or extended program). The Arimidex((R)), Tamoxifen Alone or in Combination (ATAC) trial is a landmark trial that demonstrated the superiority of upfront anastrozole over tamoxifen. This article reviews the trial and discusses both the optimum timing of initiation of aromatase inhibitors and the future approach of more individualized therapy, with the detection of predictive markers.
Chemopreventive effects of anastrozole in a premenopausal breast cancer model.
Anticancer Res. 2008 Sep-Oct; 28(5A): 2819-23
Kubatka P, Sadlonová V, Kajo K, Nosál'ová G, Ostatníková D, Adamicová K
BACKGROUND: Monotherapy with aromatase inhibitors has no established role in premenopausal breast cancer in women and is an area of future exploration. MATERIALS AND METHODS: In this study, chemopreventive effects of anastrozole in the model of N-methyl-N-nitrosourea-induced premenopausal mammary carcinogenesis in female rats were evaluated. Anastrozole was dietarily administered at two concentrations: 0.05 mg/kg (ANA 0.05) and 0.5 mg/kg (ANA 0.5). Basic parameters of experimental carcinogenesis and side-effects on selected organs after anastrozole treatment in animals were assessed. RESULTS: In the ANA 0.5 group, anastrozole suppressed tumor incidence by 40% (p
J Cancer Res Clin Oncol. 2008 Nov 26;
Okishiro M, Taguchi T, Kim SJ, Tanji Y, Shimazu K, Tamaki Y, Noguchi S
PURPOSE: Incidence of joint symptoms and bone fractures as well as changes in bone mineral density (BMD) in Japanese postmenopausal breast cancer patients treated with adjuvant anastrozole were investigated to determine whether there is an ethnic difference from Caucasian patients in the incidence of these adverse events of anastrozole. METHODS: Adjuvant anastrozole was used to treat 348 postmenopausal breast cancer patients for a median period of 22 months. Adverse events of anastrozole including joint symptoms, loss of BMD, and bone fracture were investigated by means of chart review. RESULTS: Joint symptoms developed in 96 (27.5%) patients. Age (younger than 65) and prior chemotherapy was strongly associated with an increased risk of joint symptoms. Annual fracture incidence was 0.86 and 0.85% and lumbar BMD decreased by 1.3 and 2.8% at 1 and 2 years, respectively. In comparison, the ATAC trial reported corresponding figures of 2.0 and 2.7 and of 2.2 and 4.0%. CONCLUSION: Incidence and risk factors of joint symptoms are similar for Japanese and Caucasian patients, but the former tend to show a smaller decrease in BMD and a lower incidence of bone fractures, probably due to ethnic difference in the hormonal milieu.
Neurourol Urodyn. 2008 Nov 24;
Pessina F
AIM: To study the effect of 17beta-estradiol (E(2)) as a neuroprotective agent in male and female rat urinary bladders subjected to Anoxia-Glucopenia and Reperfusion (A/G-R) damage. METHODS: Rat urinary bladders were exposed to 1 hour of A-G and 2 hours of reperfusion (R). Intrinsic nerves underwent electrical field stimulation. The effect of E(2) on the contractile response and its recovery in R phase, was monitored by adding it to the bath medium, at different concentrations, 60 min before A-G, during the A-G and the first 30 min of R. Furthermore, on both genders, in vivo treatments with E(2), testosterone, IC1 182,780 and anastrozole were performed. RESULTS: After A-G the recovery of the nerve function in female bladders were significantly higher than in male. E(2) given both in vivo (increased of E(2) plasma levels were monitored) and in vitro, resulted to be neuroprotective in male bladder subjected to A-G/R damage. When rats were treated with anastrozole, a lower recovery of nerve responses both in male and female bladders was observed. Finally, treatments with E2 receptor antagonist ICI 182,780 increased E(2) plasma levels and showed to abolished E(2) neuroprotection, thus suggesting that E2 promotes nelronal survival likely through a rapid estrogen receptor mediated response. CONCLUSIONS: Male rat urinary bladder serves are more susceptible to A-G/R damage than female. E(2) exhibits neuroprotective properties and could be a lead for novel agents capable to protect the urinary bladder from ischaemia/reperfusion damage associated with urinary bladder disorders. Neurourol. Urodynam. (c) 2008 Wiley-Liss, Inc.
Am J Obstet Gynecol. 2008 Nov 17;
Duffy SR, Distler W, Howell A, Cuzick J, Baum M
OBJECTIVE: Results of the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial have shown that tamoxifen is associated with a significantly higher incidence of gynecologic adverse events than anastrozole. STUDY DESIGN: This was a retrospective analysis of all gynecologic adverse events and interventions conducted in patients receiving anastrozole or tamoxifen in the main ATAC trial database. RESULTS: Women taking tamoxifen experienced significantly more gynecologic adverse events than those taking anastrozole (34.2% vs 20.5%; P < .0001) and this led to more diagnostic and/or therapeutic interventions, including an almost 4-fold increase in the number of hysterectomies (5.1% vs 1.3%; P < .0001). The majority of the gynecologic adverse events with tamoxifen occurred during the first 2.5 years. CONCLUSION: The lower incidence of gynecologic adverse events and interventions with anastrozole and the early occurrence of these events provide further support for using anastrozole as the initial adjuvant treatment for early hormone receptor-positive breast cancer.
Lancet Oncol. 2008 Dec; 9(12): 1143-8
Cuzick J, Sestak I, Cella D, Fallowfield L,
BACKGROUND: When the mechanism of action behind treatment toxicity reflects the intended effect on the treatment target, the toxicity might be a useful marker for efficacy. During endocrine treatment of breast cancer, the occurrence of symptoms related to oestrogen depletion or oestrogen blockade might thus be a predictor of treatment effectiveness. In this retrospective analysis, the relation between the reported incidence of vasomotor or joint symptoms and breast cancer recurrence in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial is assessed. METHODS: Women with hormone-receptor-positive tumours who reported vasomotor or joint symptoms at the first follow-up visit (3 months) in the ATAC trial, (which assessed tamoxifen or anastrozole for adjuvant treatment of postmenopausal breast cancer), were compared with women without these symptoms to see if there was a relation between these symptoms and subsequent recurrence. The ATAC trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN18233230. FINDINGS: 1486 of 3964 (37.5%) eligible women reported newly emergent vasomotor symptoms at the 3-month follow-up visit and had lower subsequent recurrence than those who did not report these symptoms (223 during 10 752 women-years of follow-up vs 366 during 11 573 woman-years of follow-up, respectively; hazard ratio [HR] 0.84 [95% CI 0.71-1.00], p=0.04; adjusted for age, body-mass index, previous hormone-replacement therapy, nodal status, tumour size, and tumour grade). A greater decrease in breast-cancer recurrence was seen for the 1245 of 3964 (31.4%) eligible women who reported new joint symptoms at the 3-month follow-up visit compared with those not reporting these symptoms (158 during 9242 women-years of follow-up vs 366 during 11 573 women-years of follow-up; adjusted HR 0.60 [0.50-0.72], p
The endocrine prevention of breast cancer.
Best Pract Res Clin Endocrinol Metab. 2008 Aug; 22(4): 615-23
Howell A
Breast cancer incidence is increasing in all parts of the world. Although in Western countries death rates are declining, there is a need to make attempts to prevent the disease in order to reduce the trauma of diagnosis and treatment. Endocrine approaches to breast cancer prevention have been the most successful approach to cancer prevention to date. Studies with tamoxifen were initiated when it was noted that, during adjuvant treatment after surgery to prevent relapse, the incidence of new contralateral cancers was reduced by half. Four trials of >or=5 years of tamoxifen compared with placebo in women at increased risk of breast cancer were initiated in the 1980s and showed a similar reduction in breast cancer, but only in oestrogen-receptor-positive disease. Recent follow-up indicated that there is a carry-over effect of tamoxifen after the completion of treatment at 5 years so that the preventive effect at 10 years is significantly great than at 5. The selective oestrogen receptor modulator (SERM) raloxifene has also been assessed as a preventive agent in two major international randomized trials compared with placebo and shows a protective effect similar to that of tamoxifen. An American study subsequently compared tamoxifen and raloxifene in a trial of nearly 20,000 women at increased risk (the STAR trial) and demonstrated that the two agents were equally effective but that the toxicity of raloxifene was less. Adjuvant trials comparing tamoxifen and the modern potent aromatase inhibitors (anastrozole, letrozole and exemestane) indicate that they are superior to tamoxifen and reduce contralateral breast cancer by approximately 70%. This observation has led to the initiation of two trials in postmenopausal women comparing anastrozole (the IBISII trial) or exemestane (the MAP-3 trial) with placebo. Currently it is recommended that tamoxifen is used to prevent breast cancer in premenopausal women and raloxifene for postmenopausal women (it is not effective in the premenopausal group),and we await the results of the aromatase inhibitor trials.
Never too late: reducing late breast cancer relapse risk.
Curr Med Res Opin. 2008 Oct 23;
Harbeck N
BACKGROUND: Breast cancer is the most common cancer diagnosed in Europe, with an estimated 429 900 new cases diagnosed in 2006. For over 20 years, tamoxifen was the standard adjuvant (postoperative) endocrine treatment for hormone receptor-positive (i.e., endocrine-responsive) early breast cancer. Yet, even after the first 5 years, patients with hormone receptor-positive tumours are at risk of relapse. Particularly in endocrine-responsive disease, most instances of relapse and breast cancer mortality occur after the first 5 years.SCOPE: Extended adjuvant aromatase inhibitor therapy (EAT) now offers postmenopausal women the opportunity to further protect themselves against late relapse.METHODS: This review summarises the clinical evidence and gives practical recommendations for discussing EAT with patients. Relevant information on patients receiving extended or late extended adjuvant endocrine therapy was obtained from databases and congress websites. The most substantial evidence for EAT is provided by the MA.17 trial using letrozole, with similar results obtained from smaller studies using anastrozole or exemestane.FINDINGS: Extended adjuvant letrozole reduced the risk of recurrence by 42% and the risk of distant metastases by 40%, it was well tolerated compared to placebo; among lymph node-positive patients, overall survival was significantly improved. Ideally, EAT should be started within 3 months of finishing tamoxifen therapy, and evidence supports its use for at least 4 years, showing increasing benefit with longer treatment duration. It is also effective, even after a longer time period, following completion of tamoxifen therapy. When deciding whether or not to use EAT after tamoxifen, clinicians and patients should consider the residual risk of relapse, comorbidities and individual preferences.
Int J Clin Oncol. 2008 Oct; 13(5): 384-94
Yamamoto Y, Iwase H
For the medical treatment of early breast cancer, aromatase inhibitors (AIs) such as anastrozole, letrozole, and exemestane are more effective than selective estrogen-receptor modulators (SERMs) such as tamoxifen (TAM). However, the adverse events associated with AIs are different from those associated with SERMs. Hot flushes, gynecological disorders, and thrombosis are more frequent in patients treated with TAM than in those treated with AIs. Conversely, osteoporosis, fractures, joint symptoms, and myalgia are more common in patients receiving AIs. Osteoporosis and bone fractures resulting from osteoporosis are important issues for patients treated with AIs. The precise management of bone health, in strict accordance with clinical guidelines, is vital in patients receiving AIs. AI-related joint symptoms are also one of the most important considerations for patients taking AIs. AI-related joint symptoms are the most common reason for the discontinuation of AIs. Confirmed management strategies for AI-related joint symptoms are unavailable at present. In patients receiving AIs, long-term adverse events (for example, those occurring as a result of changing lipid metabolism) remain unclear. There is a clear need to elucidate AI-related adverse events over the long term and to establish management strategies for AI-related adverse events, such that AIs can be used safely in patients with breast cancer over long periods of time.
Gan To Kagaku Ryoho. 2008 Oct; 35(10): 1787-9
Maruyama S, Ito M, Hirano Y, Shimo T, Hashida S, Iga K, Inukai M, Kanaya Y, Yokoyama N
A 51-year-old postmenopausal woman was referred to our hospital for treatment of ER-positive recurrent breast cancer. The patient had lung and pleural metastases with pleural effusion from breast cancer. She was treated with anastrozole, a 3rd-generation aromatiase inhibitor. The efficacy of the treatment was definite: the multiple metastatic lung lesions showed a partial response after 5 months' treatment, and reached a complete response after 14 months' treatment. The patient experienced no adverse effects with this therapy. Anastrozole therapy is a useful treatment for postmenopausal woman with ER-positive recurrent breast cancer.