Disease relevance of Anastrole

• Questions about anastrozole for early breast cancer [1].
• Moreover, anastrozole therapy avoids the weight gain associated with megestrol acetate treatment [2].
• Evaluation of tamoxifen and anastrozole in the prevention of gynecomastia and breast pain induced by bicalutamide monotherapy of prostate cancer [3].
• Compared with patients receiving tamoxifen only, patients receiving anastrozole only reported significantly fewer cold sweats and vaginal discharge, yet more vaginal dryness, painful intercourse, and loss of sexual interest [4].
• The safety and efficacy of anastrozole for the treatment of pubertal gynecomastia were evaluated [5].

Psychiatry related information on Anastrole

• Patients on anastrozole did not report higher incidences of oestrogen withdrawal symptoms [6].
• Consistent with the 2-year analysis, there were differences between treatment groups in patient-reported side effects: diarrhea (anastrozole 3.1% vs. tamoxifen 1.3%), vaginal dryness (18.5% vs. 9.1%), diminished libido (34.0% vs. 26.1%), and dyspareunia (17.3% vs. 8.1%) were significantly more frequent with anastrozole compared to tamoxifen [7].
• The anastrozole-treated patients were projected to experience a 5.6% absolute risk reduction of first breast cancer recurrence and a 2.8% absolute risk reduction in breast cancer death [8].

High impact information on Anastrole

• The potent and selective third-generation aromatase inhibitors, anastrozole, letrozole, and exemestane, were introduced into the market as endocrine therapy in postmenopausal patients failing antiestrogen therapy alone or multiple hormonal therapies [9].
• Anastrozole as a preventive agent in breast cancer [10].
• Disease-free survival at 3 years was 89.4% on anastrozole and 87.4% on tamoxifen (hazard ratio 0.83 [95% CI 0.71-0.96], p=0.013) [11].
• Estradiol also attenuated VCAM-1 mRNA expression, but this action was not abolished in the presence of anastrozole, indicating that anastrozole itself did not modulate VCAM-1 mRNA expression [12].
• PATIENTS AND METHODS: Postmenopausal women with ER-positive, invasive, nonmetastatic, and operable or locally advanced potentially operable breast cancer were randomly assigned to neoadjuvant tamoxifen (20 mg daily), anastrozole (1 mg daily), or a combination of tamoxifen and anastrozole for 3 months [13].

Chemical compound and disease context of Anastrole

• PATIENTS AND METHODS: The IMPACT trial compared the preoperative use of tamoxifen with anastrozole alone or in combination in postmenopausal women (n = 330) with primary breast cancer [14].
• PATIENTS AND METHODS: Twelve postmenopausal women with estrogen receptor-positive, metastatic breast cancer were treated with anastrozole 1 mg orally (PO) and letrozole 2.5 mg PO once daily, each given for a time interval of 6 weeks in a randomized sequence [15].
• Fulvestrant, formerly ICI 182,780, is as effective as anastrozole in postmenopausal women with advanced breast cancer progressing after prior endocrine treatment [16].
• In the adjuvant therapy setting in early breast cancer, several large, well-conducted, randomized, double-blind clinical trials have provided evidence for the value of the third-generation aromatase inhibitors (AI) anastrozole, exemestane, and letrozole [17].
• As a result, several aromatase inhibitors with a high degree of selectivity for aromatase and improved tolerability have become clinically available for the treatment of postmenopausal women with advanced breast cancer: (a) anastrozole; (b) letrozole; (c) fadrozole; (d) formestane; and (e) exemestane [18].

Biological context of Anastrole

• Concomitant treatment of UMB-1Ca cells with the signal transduction inhibitors and anastrozole and tamoxifen restored their growth inhibitory effects [19].
• Lung tumor aromatase activity was inhibited by anastrozole, an aromatase inhibitor, and treatment of tumor cells in vitro with anastrozole led to significant suppression of tumor cell growth [20].
• After 1 year of anastrozole treatment, increased bone remodeling was observed (NTX, +15%; 95% CI, 3-25%; bone ALP, +20%; 95% CI, 14-25%); decreased bone remodeling was observed with tamoxifen (NTX, -52%; 95% CI, -62% to -33%; bone ALP, -16%; 95% CI, -24% to -11%) [21].
• Further, whole genome expression patterns were studied in 12 patients treated with anastrozole [22].
• The aromatase inhibitor, Arimidex (100 nmol/L), abolishes sex differences in OGD-induced cell death, whereas treatment with 17beta-estradiol (10 nmol/L) protects cells of either sex [23].

Anatomical context of Anastrole

• CONCLUSIONS: Switching from tamoxifen to anastrozole treatment significantly reduced the need for a second hysteroscopy and D&C due to recurrent vaginal bleeding or thickening of the endometrium in postmenopausal breast cancer patients with tamoxifen-induced endometrial abnormalities [24].
• Anastrozole and testolactone have similar effects on hormonal profiles and semen analysis [25].
• Anastrozole may offer greater selectivity compared with other aromatase inhibitors, being without any intrinsic endocrine effects and with no apparent effect on the synthesis of adrenal steroids [26].
• Morphometric analysis of the normal testes at 19 weeks showed no difference in the number of Sertoli cells or germ cells, or the percentage volumes of the seminiferous epithelium, tubule lumens and interstitium between control and anastrozole-treated rats [27].
• While most of the cultured MII oocytes had a normal spindle and well aligned chromosomes, significantly less oocytes were fertilized in the groups cultured in the presence of Arimidex [28].

Associations of Anastrole with other chemical compounds

• Testosterone also attenuated TNFalpha-induced VCAM-1 protein expression, and this attenuation was abolished in the presence of anastrozole [12].
• OR rates showed a numerical advantage for fulvestrant (20.7%) over anastrozole (15.7%) (odds ratio, 1.38; CI, 0.84 to 2.29; P =.20) [16].
• Aromatase inhibitor letrozole also inhibited growth at 10,000-fold higher concentration than required for MCF-7Ca cells, whereas anastrozole, exemestane, formestane, and tamoxifen were ineffective at 100 nmol/L [19].
• For LH, the percent increase in serum levels after castration was almost 3-fold greater than that seen after selective E(2) withdrawal (275 +/- 23% with ketoconazole vs. 95.6 +/- 21% with anastrozole; P: < 0.005) [29].
• The development of the third-generation aromatase inhibitors anastrozole, letrozole, and exemestane is changing the algorithm for the treatment of the disease [30].
• The addition of a weekly tamoxifen administration did not impair anastrozole bioavailability and modulated favorably its safety profile, providing the rationale for further studies [31].
• Forty-three patients were randomized to anastrozole plus gefitinib and 50 patients were randomized to anastrozole plus placebo of a planned total of 174 patients (enrollment was prematurely discontinued due to slow recruitment) [32].

Gene context of Anastrole

• Dixon plots used to determine the Ki values for the inhibition of CYP1A2 and CYP3A activities by anastrozole were biphasic, indicating additional lower affinity Ki values [33].
• Inhibition of human drug metabolizing cytochromes P450 by anastrozole, a potent and selective inhibitor of aromatase [33].
• The anastrozole-induced changes in IGFs and IGFBP-1 appeared to be different in the patients receiving a clinical benefit from those observed in non-responders [34].
• Furthermore, the preliminary results of the Arimidex, Tamoxifen, Alone and in Combination (ATAC) study have shown that adjuvant anastrozole is superior to tamoxifen in terms of disease-free survival (DFS), non-musculoskeletal adverse effects and prevention of contralateral breast cancer in postmenopausal women with early, ER-positive breast cancer [35].
• There was a significantly greater suppression of Ki67 in the anastrozole-treated group than in the tamoxifen- or combination-treated groups, which is parallel to the greater efficacy seen for anastrozole over these two treatments in the Arimidex, Tamoxifen, Alone or in Combination adjuvant trial [14].

Analytical, diagnostic and therapeutic context of Anastrole

• The improvement in disease-free survival with anastrozole was seen in the subgroup of hormone-receptor-positive patients, but not the receptor-negative patients [11].
• Neoadjuvant treatment of postmenopausal breast cancer with anastrozole, tamoxifen, or both in combination: the Immediate Preoperative Anastrozole, Tamoxifen, or Combined with Tamoxifen (IMPACT) multicenter double-blind randomized trial [13].
• PATIENTS AND METHODS: The randomized, double-blind, multicenter study was designed to evaluate anastrozole 1 mg once daily relative to tamoxifen 20 mg once daily in patients with hormone receptor-positive tumors or tumors of unknown receptor status who were eligible for endocrine therapy [36].
• Similarly, among ovariectomized nude mice with A549 lung tumor xenografts, administration of anastrozole by p.o. gavage for 21 days elicited pronounced inhibition of tumor growth in vivo [20].
• However, more events were life threatening or required hospitalization in the tamoxifen group than in the anastrozole group (33 of 150 events v 28 of 203 events, P = .04) [37].

References