Disease relevance of Femara

• Letrozole for advanced breast cancer [1].
• Letrozole was significantly better tolerated than MA with respect to serious adverse experiences, discontinuation due to poor tolerability, cardiovascular side effects, and weight gain [2].
• Reversible pancytopenia caused by oral letrozole assumption in a patient with recurrent breast cancer [3].
• Megestrol acetate was more likely to produce weight gain, dyspnea, and vaginal bleeding, and the letrozole groups were more likely to experience headache, hair thinning, and diarrhea [4].
• These findings provide experimental evidence that letrozole is an effective and safe (in terms of risk of endometrial cancer risk and osteoporosis) alternative or complement to tamoxifen treatment for breast cancer [5].
• This preliminary study suggests that letrozole may be effective therapy in some girls with MAS and/or gonadotropin-independent precocious puberty [6].
• Genes have been identified which either change markedly or consistently in breast cancer after 14 days treatment with letrozole [7].

Psychiatry related information on Femara

• Objective: To report a case in which the aromatase inhibitor letrozole produced irritable mood elevation followed by depression in a woman with a history of postpartum depression [8].
• Letrozole Versus Testosterone. A Single-Center Pilot Study of HIV-Infected Men Who Have Sex with Men on Highly Active Anti-Retroviral Therapy (HAART) with Hypoactive Sexual Desire Disorder and Raised Estradiol Levels [9].

High impact information on Femara

• Role of androgens on MCF-7 breast cancer cell growth and on the inhibitory effect of letrozole [10].
• In xenografts, combined treatment with ER down-regulator fulvestrant and letrozole, prevented increases in erbB-2 and activation of MAPK and was highly effective in inhibiting tumor growth throughout 29 weeks of treatment [11].
• Expression of erbB-2 and p-Shc increased throughout treatment, whereas growth factor receptor binding protein 2 (Grb2) increased only in tumors proliferating on letrozole (weeks 28 and 56) [11].
• Based on promising data involving reduction of contralateral breast cancer risk in adjuvant studies, several aromatase inhibitors, including letrozole, anastrozole, and exemestane, are being incorporated into trials evaluating their efficacy as preventive agents in women at increased risk [12].
• Ovariectomized mice bearing tumor xenografts grown from aromatase-transfected estrogen receptor (ER)-positive human breast cancer cells (MCF-7Ca) were injected s.c. with 10 microg/d letrozole for up to 56 weeks [11].

Chemical compound and disease context of Femara

• PURPOSE: To analyze overall survival (OS) and update efficacy data for letrozole versus tamoxifen as first-line therapy in postmenopausal women with locally advanced or metastatic breast cancer [13].
• Influence of letrozole and anastrozole on total body aromatization and plasma estrogen levels in postmenopausal breast cancer patients evaluated in a randomized, cross-over study [14].
• CONCLUSION: This study revealed letrozole (2.5 mg once daily) to be a more potent suppressor of total-body aromatization and plasma estrogen levels compared with anastrozole (1 mg once daily) in postmenopausal women with metastatic breast cancer [14].
• CONCLUSIONS: Letrozole 2.5 mg offers longer disease control than aminoglutethimide and letrozole 0.5 mg in the treatment of postmenopausal women with advanced breast cancer, previously treated with anti-oestrogens [15].
• Thus, the Z-FAST BMD results show that upfront zoledronic acid prevents CTIBL in postmenopausal women receiving adjuvant letrozole therapy for early breast cancer [16].

Biological context of Femara

• Treatment with Let, Tam, or E2W resulted in a dose- and time-dependent increase in active caspase-7 and up-regulation of p53 and p21 protein [17].
• Similarly, SP-B levels in fetal lungs of untreated baboons were increased 10-fold between d 100 and d 165-175 of gestation in untreated baboons and baboons treated with CGS 20267 or CGS 20267 and estrogen [18].
• Impact of tamoxifen on the pharmacokinetics and endocrine effects of the aromatase inhibitor letrozole in postmenopausal women with breast cancer [19].
• Conversely, cell proliferation was stimulated by R1881 and testosterone, an effect enhanced by letrozole [20].
• A statistically significant mean decrease in bone mineral density in the hip occurred at 24 months on letrozole [21].

Anatomical context of Femara

• Patients and Methods: Stages I-IIIA breast cancer patients (n = 47) received 5 mg/d letrozole and 150-300 IU FSH to cryopreserve embryos or oocytes [22].
• In contrast, administration of CGS 20267 decreased serum estradiol (P < 0.01) and placental cytotrophoblast mRNA (2,912 +/- 693 attomoles/microg RNA; P < 0.05) levels by 75%, effects prevented by concomitant administration of CGS 20267 and estradiol [23].
• Placentas were obtained on d 60 of gestation (length of gestation is 184 d) from baboons in which estrogen levels on d 25-59 were increased by daily administration of aromatizable androstenedione or decreased by aromatase inhibitor CGS 20267 [23].
• Fetal adrenal glands were obtained at mid- (d 100) and late (d 165, term is 184 d) gestation from untreated baboons and on d 165 from animals in which endogenous estrogen production was suppressed by administration of aromatase inhibitor CGS 20267 between d 100 and 165 [24].
• In the present study the effect of letrozole on cell proliferation of estrogen receptor (ER)-positive MCF-7 human epithelial breast cancer and MCF-12A human mammary epithelial cells was studied [25].

Associations of Femara with other chemical compounds

• Total duration of endocrine therapy ("time to chemotherapy") was significantly longer (P =.005) for patients initially on letrozole (median, 16 months) than for patients initially on tamoxifen (median, 9 months) [13].
• On-treatment levels of aromatase were detectable in 11 of 12 patients during treatment with anastrozole (mean percentage inhibition in the whole group, 97.3%) but in none of the 12 patients during treatment with letrozole (> 99.1% suppression in all patients; Wilcoxon, P =.0022, comparing the two drug regimens) [14].
• Of the recombinant allozymes, only the double mutant (Arg39Cys264) displayed a significant change from the WT enzyme in inhibitor constant for the aromatase inhibitors exemestane and letrozole [26].
• This issue was evaluated by assessing the effect of a blockade of estrogen synthesis on bone turnover markers in 42 normal women (mean age +/- SD, 69 +/- 5 years) randomly assigned to groups receiving the potent aromatase inhibitor letrozole or placebo for 6 months [27].
• In both age groups, letrozole, but not placebo, significantly increased LH levels (339 and 323% in the young and the elderly, respectively) and T (146 and 99%, respectively) (P value of young vs. elderly was not significant) [28].
• Letrozole consistently suppressed each plasma estrogen fraction below the levels recorded for anastrozole: E(2) (average suppression by 95.2% versus 92.8%; P = 0.018), E(1) (98.8% suppression versus 96.3%; P = 0.003), and E(1)S (98.9% suppression versus 95.3%; P = 0.003) [29].
• In the L-BLP25 plus letrozole treatment group, statistically significant (P < 0.05) additive antitumor activity was observed, whereas tamoxifen plus L-BLP25 was not significantly different (P > 0.05) [30].

Gene context of Femara

• Activation of mitogen-activated protein kinase in xenografts and cells during prolonged treatment with aromatase inhibitor letrozole [11].
• Twenty-three of 92 tumors (25%) on tamoxifen and 14 of 93 on letrozole (15%) showed a paradoxical increase in Ki67 with treatment, and the majority of these cases was HER1/2 negative [31].
• Aromatase is the enzyme responsible for the conversion of androgens into estrogens, and synthetic aromatase inhibitors such as letrozole, anastrozole, and exemestane have proven to be effective endocrine regimens for ER-positive breast cancer [32].
• We have investigated the effect of HER-2 overexpression on resistance to the aromatase inhibitor letrozole in MCF-7 breast cancer cells stably expressing cellular aromatase (MCF-7/CA) [33].
• We have previously shown that letrozole (a different type of NSS-AI) modifies blood IGF-1 levels, and the results of this study of the biological effects of anastrozole on the components of the IGF system confirm our previous observations [34].

Analytical, diagnostic and therapeutic context of Femara

• Fertility preservation in breast cancer patients: a prospective controlled comparison of ovarian stimulation with tamoxifen and letrozole for embryo cryopreservation [35].
• Letrozole 2.5 mg was significantly superior to MA and letrozole 0.5 mg in time to treatment failure (P = .04 and P = .002, respectively) [2].
• RESULTS: For study biopsy-confirmed ER+ and/or PgR+ cases that received letrozole, 60% responded and 48% underwent successful breast-conserving surgery [36].
• CONCLUSIONS: Letrozole administration led to a statistically significant prolongation in disease-free survival [21].
• Clinical trials combining tamoxifen with letrozole or anastrazole have shown minor pharmacokinetic drug interactions [37].

References