Months Of Letrozole Research Articles

Reduction in proliferation with six months of letrozole in women on hormone replacement therapy

The objective of this study was to determine if 6 months of the aromatase inhibitor letrozole, administered to postmenopausal women taking a stable dose of hormone replacement remedy, would be safe and would modulate biomarkers of breast cancer risk. The intent was to reduce the proliferation marker Ki-67 while maintaining adequate systemic levels of estradiol so as to avoid perimenopausal symptoms. Postmenopausal women at high risk for development of breast cancer and taking a stable dose of estrogen or estrogen plus progestin were screened by random periareolar fine needle aspiration (RPFNA). To be eligible, the acquired breast epithelial cells had to be characterized as cytologic atypia or borderline atypia with > or =1,000 epithelial cells on the cytomorphology slide; plus > or =500 epithelial cells on a slide processed for Ki-67 immunocytochemistry. Forty-two women were enrolled in the one arm study and received 2.5 mg letrozole per day for 6 months, followed by repeat assessment of biomarkers. Ki-67 was reduced by a median relative value of 66%. There was no significant change in breast cell cytomorphology; ER weighted index score; serum estradiol, testosterone, or IGF-1:IGFBP-3 ratio; mammographic breast density, or frequency or severity of perimenopausal symptoms. Given the dramatic reduction in proliferation, the effect of letrozole on risk and response biomarkers should be explored further in a randomized, placebo-controlled Phase IIB breast cancer chemoprevention trial.

Quality-adjusted survival in a crossover trial of letrozole versus tamoxifen in postmenopausal women with advanced breast cancer

Results from a phase III study of postmenopausal women with advanced breast cancer demonstrated longer time to disease progression for patients taking letrozole versus tamoxifen. This analysis compares the trade-offs between progression-free survival and toxicity. Quality-adjusted survival was calculated using Q-TWiST (quality-adjusted time without symptoms or toxicity). Survival curves were partitioned into three health states: toxicity (TOX), disease progression (PROG) and periods without toxicity or disease progression (TWiST). The utility-weighted sum of the health state durations was derived and compared. There was not a significant difference in mean duration of serious adverse events prior to progression between the letrozole (n=453) and tamoxifen (n=454) groups (2.2 and 2 months, respectively). For TWiST, the mean duration for letrozole was 11.5 months, versus 8.5 months for tamoxifen (P <0.001). The mean duration of PROG was 11.5 months for letrozole and 12.7 months for tamoxifen (P=0.047). Using utility weights of 0.5 for TOX and PROG resulted in a 2.5-month difference in quality-adjusted survival favoring letrozole (P <0.0001). The longer time to disease progression with letrozole versus tamoxifen was achieved without increased time with adverse events and resulted in more quality-adjusted survival for patients on letrozole.

Letrozole versus tamoxifen in the treatment of advanced breast cancer and as neoadjuvant therapy

Letrozole, a third generation aromatase inhibitor, has been compared with tamoxifen in the treatment of advanced breast cancer and as neoadjuvant therapy. In a first-line trial in advanced disease, 939 post menopausal women were randomised double blind to receive treatment with letrozole 2.5 mg daily or tamoxifen 20 mg daily. Letrozole was significantly superior in terms of median time to progression (9.4 months versus 6.1 months, P = 0.0001), objective response (30% versus 20%, P = 0.0006), and clinical benefit (49% versus 38%, P = 0.0001). Superiority of letrozole was independent of disease site, receptor status, or prior adjuvant anti-oestrogen therapy. In an extended phase of this trial, 200 patients were crossed over to tamoxifen after letrozole, compared with 197 crossed over to letrozole after tamoxifen. Median overall survival was 34 months for letrozole versus 30 months for tamoxifen (not significant). In a similar randomised double-blind neoadjuvant trial, 337 post menopausal patients with large ER/or PgR positive T2–T4 cancers, either requiring mastectomy or locally advanced, were randomised to preoperative letrozole or tamoxifen for 4 months prior to surgery. Overall response was 55% for letrozole versus 36% for tamoxifen ( P < 0.001). Conservative surgery was possible in 45% of patients treated with letrozole versus 35% with tamoxifen ( P = 0.022). In both trials, both treatments were well tolerated with no significant differences in side effects. These results indicate that letrozole is more active than tamoxifen both as neoadjuvant therapy and as first-line treatment in advanced disease. They support the importance of current adjuvant trials comparing the two treatments.

Cost Effectiveness of Letrozole in the Treatment of Advanced Breast Cancer in Postmenopausal Women in the UK

To simulate the treatment of postmenopausal women with advanced breast cancer from second-line hormone therapy to death, and to generate estimates of the cost and effectiveness of letrozole and megestrol in order to determine the incremental cost effectiveness of letrozole, expressed as cost per life-years gained. A decision-analytic model, using Markov process techniques, was designed to evaluate the lifetime clinical and economic consequences of treatment with letrozole compared with standard care with megestrol. The model was based on clinical trial results showing a clear advantage of letrozole in terms of time to progression and duration of response. The setting of the study was that of the UK healthcare system in 1996. A hypothetical cohort of patients, identical to the patients recruited for the AR/BC2 clinical trial, who were postmenopausal women with advanced breast cancer who had previously failed to respond to first-line or adjuvant anti-estrogen therapy. The dosages of medications were 2.5 and 160 mg/day for letrozole and megestrol, respectively. The analysis covered the period from treatment initiation until death (lifetime model). Effectiveness was expressed as survival and time without progression, and the model also included all relevant economic measures. Based on the model, the average survival time of the letrozole group was 2.1 years (25.3 months) versus 1.9 years (21.5 months) for the megestrol group, a gain in survival of 2.4 months (10.5%). The average time without progression, cumulatively calculated over the different treatment options, amounted to 20.2 months for letrozole and 17.8 months for megestrol, an increase of 13.7% for the former patients. The total average cost per patient for the treatment of advanced breast cancer starting from second-line hormone therapy until death was higher in the letrozole group at 7547 Pounds versus 6820 Pounds for the megestrol group (discounted at an annual rate of 5%), leading to an incremental cost-effectiveness ratio of 3588 Pounds per life-year gained (1996 values). Based on the assumptions used in this model, letrozole offers a suitable alternative to megestrol in the treatment of second-line hormone therapy.