The what, why and how of aromatase inhibitors - review article

Information about conventional breast cancer treatments - inc surgery, chemo, rads, hormonal, reconstruction, lymphedema, side effects
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jayem
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Postby jayem » Thu Sep 27, 2007 5:56 pm

Janine, thank you so much. As I am on Arimidex there is much information in this article that I want to know and understand.
You are indeed on top of the latest information for us. Thank you once again. :clap:
Jan

Dx 20 Sept 2006, 2 cm IDC + DCIS, 1/16+ node, ER+, PR+, HER2-, 4 AC, 4 Taxol, 33 rads
CFEM Trial 5 years Arimidex, 5 year SOLE trial Femara
Dx Aug 2016 neuroendocrine cancer in pancreas, mets to liver, abdominal nodes, hip, skull, scalp and breast.

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Postby Shell225 » Thu Sep 27, 2007 1:57 pm

Thank you Janine..really appreciate this information. Michelle

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The what, why and how of aromatase inhibitors - review article

Postby Janine » Thu Sep 27, 2007 1:40 pm

[I found this article very informative. How the AI's work, side effects, etc.. - long and a bit technical.]

C. J. Fabian
The what, why and how of aromatase inhibitors: hormonal agents for treatment and prevention of breast cancer
International Journal of Clinical Practice (OnlineEarly Articles).
doi:10.1111/j.1742-1241.2007.01587.x


C. J. Fabian Breast Cancer Prevention Center, Division of Clinical Oncology, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, USA

Summary:
The third-generation aromatase inhibitors (AIs) anastrozole, exemestane and letrozole have largely replaced tamoxifen as the preferred treatment for hormone receptor – positive breast cancer in postmenopausal women. Approximately 185,000 new cases of invasive breast cancer are diagnosed yearly, and at least half of these women are both postmenopausal and eligible for adjuvant therapy with AIs. In addition, AIs are currently being tested as primary prevention therapy in large randomised trials involving tens of thousands of women at increased risk for breast cancer. Given the volume of use, internists will increasingly see postmenopausal women who are taking or considering treatment with AIs. Physicians need to be able to: (i) briefly discuss the pros and cons of using a selective estrogen receptor modulator such as tamoxifen or raloxifene vs. an AI for risk reduction and (ii) recognise and manage AI-associated adverse events. The primary purpose of this review is to help internists with these two tasks.

Review Criteria:
Expert opinion based on review of literature on relevant clinical trials.

Introduction
Estrogen promotes the growth and survival of normal and cancerous breast epithelial cells by binding and activating the estrogen receptor (ER). The activated receptor in turn binds to gene promoters in the nucleus and activates many other genes responsible for cell division, inhibition of cell death, new blood vessel formation and protease activity. An increase in the proportion of cells that express ER is found at both the earliest stages of breast precancer and in approximately 70% of breast cancers (1). There are three ways in which estrogen-dependent processes important in the development and progression of the majority of breast cancers may be interrupted (Figure 1). The first is to interfere with the binding of estrogen to the ER and/or to the promoter elements of the genes it regulates. Selective ER modulators such as tamoxifen and raloxifene act in this manner. A second method is to reduce or eliminate ER expression. This is exemplified by fulvestrant, a selective ER down-regulator, which works by making less receptor available for binding to estrogen. The most direct means is to simply reduce the amount of estrogen by interfering with its production, via ovarian ablation in premenopausal women and use of aromatase inhibitors or inactivators (AIs) in postmenopausal women. Because of their effectiveness, AIs are quickly becoming the most frequently used antihormonal treatment for breast cancer in postmenopausal women. Further, AIs are now being tested in breast cancer prevention trials.

Aromatase inhibitors are not without adverse effects, which primarily stem from profound estrogen depletion. Many women will turn to their internists for advice about whether to take these drugs, as well as help in preventing and managing adverse events. The purpose of this article is to provide primary care physicians with a basic understanding of AIs to help facilitate these interactions.
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