Anastrozole is a selective 3rd generation nonsteroidal aromatase Inhibitor [1]. Anastrozole is indicated in treatment of early and advanced breast cancer in post-menopausal women, adjuvant therapy of hormone receptor positive breast cancer, metastatic breast cancer and tenderness of pubertal gynecomastia [2,4,5]. The main type of breast cancer is hormone receptor positive breast cancer, which is caused by an increase of oestrogen levels in the body [3] this is because oestrogen causes an increase in tumour growth. The primary source of oestrogen comes from the peripheral tissues in post-menopausal women. Lowering the levels of oestrogen in the body is an effective treatment in treating breast cancer in post-menopausal women.
Structure: …show more content…
The drug contains a 1,2,4-triazole ring which allows the triazole nitrogen (N-4) of anastrozole to coordinate with a heme iron on the active site of aromatase, this interaction is the primary interaction between anastrozole and the active site of aromatase [6]. Another interaction between the drug and aromatase is hydrogen bonding; this occurs between the triazole nitrogen (N-1) of anastrozole and the T310 residue in the active site of aromatase and between the cyano group (C-N) of anastrozole and the D309 residue [6,7]. The final interactions between anastrozole and aromatase occurs with both cyanoisopropyl groups; one cyanoisopropyl group occupies the space near the B’-C loop while the other cyanoisoproply group fits between the beta-4 sheet and I helix …show more content…
The ATAC trial looked at the effectiveness of anastrozole and tamoxifen in monotherapy and in combination with each other [1,2,5,15]. The study trailed 9366 postmenopausal women with operable breast cancer and found that anastrozole was statically superior to tamoxifen when looking at recurrence- free survival (secondary end-point) in patients who were receptor positive. The trail also found that anastrozole reduced the incidence of contra-lateral breast cancer and increased the recurrence time. While looking at the effectiveness of a combination therapy of anastrozole and tamoxifen, they found no efficacy benefit of a combination therapy. Further analysis of the anastrozole shows that there was fewer side effects experienced when compared with tamoxifen. The data shows the long-term efficacy and safety of taking anastrozole over tamoxifen as initial therapy in post-menopausal women with a receptor positive status [15]. Other studies have also supported the ATAC trial in showing the benefit of taking anastrozole over tamoxifen due to the safety and overall statically being a better drug
Structure: …show more content…
The drug contains a 1,2,4-triazole ring which allows the triazole nitrogen (N-4) of anastrozole to coordinate with a heme iron on the active site of aromatase, this interaction is the primary interaction between anastrozole and the active site of aromatase [6]. Another interaction between the drug and aromatase is hydrogen bonding; this occurs between the triazole nitrogen (N-1) of anastrozole and the T310 residue in the active site of aromatase and between the cyano group (C-N) of anastrozole and the D309 residue [6,7]. The final interactions between anastrozole and aromatase occurs with both cyanoisopropyl groups; one cyanoisopropyl group occupies the space near the B’-C loop while the other cyanoisoproply group fits between the beta-4 sheet and I helix …show more content…
The ATAC trial looked at the effectiveness of anastrozole and tamoxifen in monotherapy and in combination with each other [1,2,5,15]. The study trailed 9366 postmenopausal women with operable breast cancer and found that anastrozole was statically superior to tamoxifen when looking at recurrence- free survival (secondary end-point) in patients who were receptor positive. The trail also found that anastrozole reduced the incidence of contra-lateral breast cancer and increased the recurrence time. While looking at the effectiveness of a combination therapy of anastrozole and tamoxifen, they found no efficacy benefit of a combination therapy. Further analysis of the anastrozole shows that there was fewer side effects experienced when compared with tamoxifen. The data shows the long-term efficacy and safety of taking anastrozole over tamoxifen as initial therapy in post-menopausal women with a receptor positive status [15]. Other studies have also supported the ATAC trial in showing the benefit of taking anastrozole over tamoxifen due to the safety and overall statically being a better drug