Pre-menopausal breast cancer and aromatase inhibitors: treating a new generation of women

2006 ◽  
Vol 99 (3) ◽  
pp. 241-247 ◽  
Author(s):  
O.C. Freedman ◽  
S. Verma ◽  
M.J. Clemons
Keyword(s):  
Breast Cancer ◽  
Aromatase Inhibitors ◽  
New Generation

Current perspectives on aromatase inhibitors in breast cancer.

1994 ◽  
Vol 12 (11) ◽  
pp. 2460-2470 ◽  
Author(s):  
P E Goss ◽  
K M Gwyn
Keyword(s):  
Breast Cancer ◽  
Aromatase Inhibitors ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Future Application ◽  
In Vivo Experiments ◽  
Estrogen Production ◽  
New Generation

PURPOSE AND DESIGN: One way to deprive hormone-dependent breast cancer of estrogen is to prevent its synthesis. This is achievable by inhibiting the aromatase cytochrome P-450 (P-450arom) enzyme complex responsible for the ultimate step in estrogen production. A new generation of specific and selective aromatase inhibitors is currently under investigation. The purpose of this review is to outline the preclinical test systems for screening these inhibitors, to summarize the preclinical and clinical data published to date, and to discuss the future application of these inhibitors in the management of breast cancer. RESULTS AND CONCLUSION: Disadvantages to the use of earlier inhibitors are described. In vitro and in vivo experiments that reflect the potency and selectivity of new inhibitors are highlighted. From preliminary clinical trials, these inhibitors appear to have excellent pharmacokinetic profiles and produce few side effects when administered orally. Activity against postmenopausal metastatic breast cancer has been demonstrated for the agents reviewed. They are all now in phase III testing to determine their relative efficacy in this setting. Their application in combination with both hormone therapy and chemotherapy, in premenopausal metastatic disease, and in the adjuvant setting in both premenopausal and postmenopausal women remains to be defined.

Status of aromatase inhibitors in relation to other breast cancer treatment modalities.

1999 ◽  
pp. 277-291 ◽  
Author(s):  
J Ragaz
Keyword(s):  
Breast Cancer ◽  
Aromatase Inhibitors ◽  
Breast Cancer Survivors ◽  
Treatment Modalities ◽  
Laboratory Research ◽  
Therapeutic Ratio ◽  
Estrogen Receptor Modulators ◽  
Beneficial Impact ◽  
Impact On Survival ◽  
New Generation

Aromatase is one of the key enzymes possibly linked with the perpetuation or even initiation of breast cancer. Modulation of its activity by the new generation inhibitors has resulted in increased responses and improved therapeutic ratio compared with those of parent aromatase inhibitors. More recent trials have shown promising results with regard to improved therapeutic ratio compared with what is seen with presently accepted second-line hormonal approaches. Present data and laboratory research indicate that new aromatase inhibitors have the potential to play an important role as adjuvants, and possibly in the prevention of human breast cancer. It is probable that it may be as adjuvants that their real therapeutic strength in terms of a beneficial impact on survival may be realized. The absence of estrogen agonist activity of new aromatase inhibitors on lipid and bone metabolism calls for more clinical studies having late mortality in breast cancer survivors as the ultimate outcome objective; in this regard, interaction of new aromatase inhibitors with new selective estrogen receptor modulators looks promising. Achievement of these outcomes, and understanding of interactions with other therapies, await the termination of present trials and the start of new initiatives.

Use of aromatase inhibitors in the adjuvant treatment of breast cancer.

1999 ◽  
pp. 231-234 ◽  
Author(s):  
M Baum
Keyword(s):  
Breast Cancer ◽  
Side Effects ◽  
Postmenopausal Women ◽  
Early Breast Cancer ◽  
Aromatase Inhibitors ◽  
Endocrine Treatment ◽  
Pharmacological Properties ◽  
Superior Efficacy ◽  
New Generation ◽  
Visual Disturbances

The value of endocrine treatment of early breast cancer has been illustrated by the antioestrogen, tamoxifen, which has now been available for nearly 30 years. However, if the recognised side effects and pharmacological properties of tamoxifen are taken into consideration, it is possible that other endocrine treatments that are now available can provide equal or superior efficacy, along with improved tolerability. One such group of agents is the aromatase inhibitors specifically the new-generation triazole aromatase inhibitors, such as anastrozole and letrozole, which have both shown tolerability and efficacy advantages over standard treatments in postmenopausal women with advanced breast cancer. There are convincing reasons why the new generation of aromatase inhibitors have advantages over tamoxifen. For instance, from their agonist properties, the effects on the endometrium and tumour stimulation seen with tamoxifen would not be expected, nor would the visual disturbances that have been associated with the triphenylethylene compounds, including tamoxifen. A number of aromatase inhibitors, for instance, anastrozole, letrozole and exemestane, are currently being investigated for treatment of early breast cancer. The results of the trials of aromatase inhibitors and tamoxifen will, in the next few years, define whether or not the new-generation aromatase inhibitors have a role to play in the treatment of postmenopausal women with early breast cancer.

Role of aromatase inhibitors in advanced breast cancer.

1999 ◽  
pp. 219-225 ◽  
Author(s):  
A U Buzdar
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Postmenopausal Women ◽  
Aromatase Inhibitors ◽  
Advanced Breast ◽  
Cross Resistance ◽  
Full Potential ◽  
Large Program ◽  
Steroidal Aromatase Inhibitors ◽  
New Generation

A number of potent and selective non-steroidal aromatase inhibitors are now available for treatment of advanced breast cancer in postmenopausal women, of which anastrozole and letrozole, in particular, represent a significant advantage over the earlier agents in terms of both efficacy and tolerability. These agents are rapidly becoming established as the second-line therapy of choice in postmenopausal women with advanced disease, progressing on tamoxifen, and data on their efficacy as first-line treatment compared with tamoxifen will be available in the near future. Exemestane, a new, steroidal aromatase inhibitor which potentially lacks cross-resistance with non-steroidal agents is still in clinical development. The full potential of the new-generation aromatase inhibitors in the treatment of breast cancer is currently being investigated in a large program of clinical trials evaluating their use as adjuvant treatment following surgery in postmenopausal patients with early disease.

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