A third generation aromatase inhibitor that blocks the synthesis of estrogen.

Brand name Femara.

May be associated with fatigue and dizziness.

Postmenopausal women who have completed 5 years of adjuvant tamoxifen therapy benefit from treatment with letrozole with a 43% reduction in recurrences and new breast cancers compared to placebo.

Superiority over Tamoxifen in metastatic breast cancer in postmenopausal women associated first line endocrine therapy.

Superior to tamoxifen as a neoadjuvant therapy in breast cancer.

Breast International Group (BIG) 1-98 trial randomized, double blind trial comparing 5 year of initial adjuvant therapy with letrozole or tamoxifen in postmenopausal women with hormone positive operable breast cancer who completed surgical management: letrozole decreased disease free survival by 19%, risk of recurrence by 28% and distant recurrence by 27% compared to tamoxifen.

Breast International Group (BIG) 1-98 trial: randomization to receive adjuvant tamoxifen for 5 years, adjuvant letrozole for 5 years, tamoxifen for 2 years followed bt letrozole for 3 years or letrozole for 2 years followed by tamoxifen for 3 years.

BIG1-98 study at median follow-up at 74 months adjuvant letrozole, compared to tamoxifen, significantly reduces the risk of death, recurrence of disease, and risk of recurrence at distant sites in postmenopausal women with hormone receptor positive breast cancer (Colleoni M et al).

BIG 1-98 trial involved more than 8000 postmenopausal ER positive early breast cancer: recurrence peaked early recurrence among women receiving adjuvant tamoxifen, the most common early recurrence event was distant metastasis.

In the above BIG 1-98 study had lower risk of endometrial cancer, and thromboembolism, but increased risk of fractures, hypercholesterolemia, and grades 3-5 cardiac events compared to tamoxifen.

Associated with a non-significant increase in total cholesterol and HDL cholesterol after three months which returns to baseline after six months (Zidan J et al).

Associated with increased LDL cholesterol which was not significant after six months and returns to baseline thereafter(Zidan J et al).

Suppresses estradiol levels maximally within six months of treatment.

In the BIG1-98 study sequential treatment of Letrozole and tamoxifen did not improve disease free survival compared to Letrozole alone.

In theBIG1-98 study and the most common early recurrence event was distant metastases: the letrozole group was associated with a 27% reduction in the risk of distant metastases versus tamoxifen. In the BIG1-98 study letrozole decreased the risk of distant metastases early on in the study. Letrozole is the only aromatase inhibitor shown to significantly reduce the risk of early distant metastases versus tamoxifen when used as initial adjuvant therapy in postmenopausal patients with hormone receptor positive early breast cancer ( Thurlimann B).

MA-17 Study randomized double blind study of letrozole 2.5 mg/d following 5 years of tamoxifen as an extended treatment for postmenopausal women with ER positive primary breast cancer vs. placebo involving 5,126 patients: women treated with letrozole had significant improved disease free and distant disease free survival, with no change in overall survival except in women with positive lymph nodes who had significant improvement.

Monotherapy Arms Analysis (MAA) demonstrated significant long term improvement of disease free survival and significant long term reduction in risk of metastasis for Letrozole compared with tamoxifen.

In the ZO-FAST study ( Zometa-Femara Adjutant Synergy Trial), and open labeled randomized phase 3 trial of 1065 postmenopausal women with early breast cancer receiving letrozole 2.5 mg a day for five years were randomized to receive zoledronic acid immediately or zoledronic acid if they are BMD T score fell below -2 or a fragility fracture was present: the mean change of L2-L4 BMD at 36 months was +4.39% for the immediate treatment group versus -4.9% for the delayed treatment group, and the disease free survival was significantly improved in the immediate treatment arm compared with the delayed treatment arm (Eidtmann et al).

In the above study the immediate treatment group at 36 months had a 41% relative risk reduction for disease free survival events.

Adding the tyrosine kinase inhibitor dasatinib to standard aromatase inhibitor therapy with letrozole doubles progression-free survival (PFS) compared with letrozole alone in women with hormone receptor-positive, HER2-negative metastatic breast cancer.

B-42 trial showed that extended adjuvant endocrine therapy improved disease free survival compared with placebo among postmenopausal women with hormone receptor positive breast cancer who completed previous adjuvant therapy with the aromatase inhibitor-10 year study.

have you been in the cream therapy with lectures or improved disease free survival compared with p a receptor positive breast cancer who completed previous Edg2242in therapy with an aromatase inhibitor‘s-a ten-year result. adjuvant endocrine

Dose 2.5 mg tablet daily.

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