MCH - OB/GYN Chief Clinical Coordinator's Corner

Maternal Child Health ‹ CCC Corner ‹ Dec 2008/Jan 2009

OB/GYN CCC Corner - Maternal Child Health for American Indians and Alaska Natives

Volume 6, No. 12, December 2008/January 2009

Abstract of the Month

Are all aromatase inhibitors alike?

The anti-estrogen tamoxifen was the gold-standard adjuvant therapy for hormone-receptor-positive (HR+) early breast cancer for several decades, but has recently been displaced by the third-generation aromatase inhibitors (AIs). Three AIs are commercially available: letrozole, anastrozole and exemestane. All are more effective and at least as well tolerated as tamoxifen as adjuvant therapy for HR+ breast cancer in postmenopausal women. Despite the wealth of data comparing AIs with tamoxifen, it is unclear whether the three AIs are clinically equivalent, owing to the lack of head-to-head trials directly comparing them. Preclinical and small clinical studies suggest that letrozole is the most potent inhibitor of aromatase, reducing circulating estrogen levels to a greater degree than the other agents. However, whether this greater activity translates into superior clinical efficacy remains to be determined. In the absence of direct comparative data, cross-trial comparisons have been used to gain insights into any safety or efficacy differences. All three AIs have been compared directly with tamoxifen, and efficacy relative to tamoxifen has been compared across trials, although such analyses are complicated by differences in treatment schedules, patient populations and trial designs. Definitive conclusions cannot yet be drawn, but some important differences are coming to light, with upfront letrozole appearing particularly effective at preventing early distant metastasis, an event strongly associated with breast-cancer-related death. No safety differences between the AIs have yet been identified. This article explores the pharmacologic and clinical differences between the AIs, based on data from clinical and preclinical studies.

Blackwell KL. Are all aromatase inhibitors alike? Breast Cancer Res Treat. 2008 Dec 20. [Epub ahead of print] http://www.ncbi.nlm.nih.gov/pubmed/19101793

OB/GYN CCC Editorial comment:

We are fortunate to have guest editorialists for this issue who are experts in the treatment of breast cancer. Laura Tillman, MD and Shannon Myers, FNP direct a Breast Clinic at Phoenix Indian Medical Center that is a model practice within the IHS. They have provided the following overview of Hormone Therapy in Breast Cancer for your consideration.

Hormone Therapy in Breast Cancer

SERMs – Selective Estrogen Receptor Modulators and AIs - Aromatase Inhibitors
Hormone therapy is a form of systemic therapy for breast cancer. It can be used as adjuvant therapy to reduce risk of recurrence but may also be used for treatment in more advanced breast cancers. Selective Estrogen Receptor Modulators (SERMs) and Aromatase Inhibitors (AIs) are two main classes of hormonal drugs used for breast cancer. Both SERMs and AIs are used to treat estrogen receptor positive (ER+) breast cancer.

SERMs are selective estrogen-receptor modulators, or drugs that block the naturally circulating estrogen in breast tissues and other estrogen-sensitive tissues in your body. SERMs are called "selective" because they bind to particular estrogen receptors. This selective binding action is sometimes called estrogen inhibition, or estrogen suppression. SERMs do not prevent the production of estrogen, but they help to slow or stop the growth of estrogen-sensitive cancer cells by starving them of a full dose of natural estrogen.

Tamoxifen was the first SERM produced, and has been in use for over 30 years. Initially, it was used in metastatic disease, but we now know that it is effective in reducing recurrence of primary breast cancer and improving overall survival in both postmenopausal and premenopausal women. It has also been shown to reduce the incidence of recurrence of breast cancer in the contralateral breast. Tamoxifen is prescribed for 5 years and there are now studies looking at the use of tamoxifen for even longer periods of time. More recently, tamoxifen has been approved in the United States as a prevention strategy for women at high risk for developing breast cancer. However, it does have side effects. The most serious side effects are blood clots, stroke, uterine cancer and cataracts. The most common side effects are hot flashes and vaginal dryness.

Aromatase Inhibitors have a different mechanism of action than SERMs. AIs prevent estrogen production instead of blocking estrogen receptors the way SERMs do. AIs reduce the amount of estrogen in the body. AIs do not block estrogen production by the ovaries, but they can block other tissues from making this hormone. That is why AIs are used in women who are in menopause, when the ovaries are no longer producing estrogen. AIs may be used as a first-line therapy or after treatment with tamoxifen. Currently, there are three AIs approved by the U.S. Food and Drug Administration: anastrazole (Arimidex), exemestane (Aromasin) and letrozole (Femara). The most serious side effect is bone thinning (osteoporosis). The most common side effects are hot flashes and body aches.

For more information about the use of SERMs and AIs and about breast cancer in American Indian and Alaska Native women, please consult the articles below or contact Dr. Tillman or Ms. Myers at Phoenix Indian Medical Center. Laura.Tillman@ihs.gov; Shannon.Myers@ihs.gov.

Carpenter R. Choosing early adjuvant therapy for postmenopausal women with hormone-sensitive breast cancer: aromatase inhibitors versus tamoxifen. Eur J Surg Oncol. 2008 Jul;34(7):746-55. Epub 2008 Mar 4. http://www.ncbi.nlm.nih.gov/pubmed/18296017

Buijs C, de Vries EG, Mourits MJ, Willemse PH. The influence of endocrine treatments for breast cancer on health-related quality of life. Cancer Treat Rev. 2008 Nov;34(7):640-55. Epub 2008 Jun 2. http://www.ncbi.nlm.nih.gov/pubmed/18514425

Breast International Group (BIG) 1-98 Collaborative Group, Thürlimann B, Keshaviah A, Coates AS, Mouridsen H, Mauriac L, et al. A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N Engl J Med. 2005 Dec 29;353(26):2747-57. http://www.ncbi.nlm.nih.gov/pubmed/16382061

Wingo PA, King J, Swan J, Coughlin SS, Kaur JS, Erb-Alvarez JA, Jackson-Thompson J, Arambula Solomon TG. Breast cancer incidence among American Indian and Alaska Native women: US, 1999-2004. Cancer. 2008 Sep 1;113(5 Suppl):1191-202.
http://www.ncbi.nlm.nih.gov/pubmed/18720389

Tillman L, Myers S, Pockaj B, Perry C, Bay RC, Al-kasspooles M. Breast cancer in Native American women treated at an urban-based Indian health referral center 1982-2003. Am J Surg. 2005 Dec;190(6):895-902. http://www.ncbi.nlm.nih.gov/pubmed/16307942

Flum DR, Stuart S, Wilcox M. Processes and outcomes of care among Navajo women with breast cancer. JAMA. 2003 Oct 15;290(15):1996-7. http://www.ncbi.nlm.nih.gov/pubmed/14559952
Free Full Text: http://jama.ama-assn.org/cgi/content/full/290/15/1996-a

MedScape CME: Comprehensive Breast Care: An Update for the Menopause Practitioner http://www.medscape.com/viewprogram/17686

Contents Summary ‹ Previous | Next › From Your Colleagues

OB/GYN

Jean Howe, MD, MPH is the Obstetrics and Gynecology Chief Clinical Consultant (OB/GYN C.C.C.). Dr. Howe is very interested in establishing a dialogue and/or networking with anyone involved in women's health or maternal child health, especially as it applies to American Indian and Alaska Native women and also indigenous peoples around the world. Please don't hesitate to contact her by e-mail (jean.howe@ihs.gov) or phone at (928) 674-7422.

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Volume 6, No. 12, December 2008/January 2009

Abstract of the Month

OB/GYN CCC Editorial comment:

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	Maternal Child Maternal Child Health ‹ CCC Corner ‹ Dec 2008/Jan 2009 Volume 6, No. 12, December 2008/January 2009 Abstract of the Month \| From Your Colleagues \| Hot Topics \| Features Abstract of the Month Are all aromatase inhibitors alike? The anti-estrogen tamoxifen was the gold-standard adjuvant therapy for hormone-receptor-positive (HR+) early breast cancer for several decades, but has recently been displaced by the third-generation aromatase inhibitors (AIs). Three AIs are commercially available: letrozole, anastrozole and exemestane. All are more effective and at least as well tolerated as tamoxifen as adjuvant therapy for HR+ breast cancer in postmenopausal women. Despite the wealth of data comparing AIs with tamoxifen, it is unclear whether the three AIs are clinically equivalent, owing to the lack of head-to-head trials directly comparing them. Preclinical and small clinical studies suggest that letrozole is the most potent inhibitor of aromatase, reducing circulating estrogen levels to a greater degree than the other agents. However, whether this greater activity translates into superior clinical efficacy remains to be determined. In the absence of direct comparative data, cross-trial comparisons have been used to gain insights into any safety or efficacy differences. All three AIs have been compared directly with tamoxifen, and efficacy relative to tamoxifen has been compared across trials, although such analyses are complicated by differences in treatment schedules, patient populations and trial designs. Definitive conclusions cannot yet be drawn, but some important differences are coming to light, with upfront letrozole appearing particularly effective at preventing early distant metastasis, an event strongly associated with breast-cancer-related death. No safety differences between the AIs have yet been identified. This article explores the pharmacologic and clinical differences between the AIs, based on data from clinical and preclinical studies. Blackwell KL. Are all aromatase inhibitors alike? Breast Cancer Res Treat. 2008 Dec 20. [Epub ahead of print] http://www.ncbi.nlm.nih.gov/pubmed/19101793 OB/GYN CCC Editorial comment: We are fortunate to have guest editorialists for this issue who are experts in the treatment of breast cancer. Laura Tillman, MD and Shannon Myers, FNP direct a Breast Clinic at Phoenix Indian Medical Center that is a model practice within the IHS. They have provided the following overview of Hormone Therapy in Breast Cancer for your consideration. Hormone Therapy in Breast Cancer SERMs – Selective Estrogen Receptor Modulators and AIs - Aromatase Inhibitors Hormone therapy is a form of systemic therapy for breast cancer. It can be used as adjuvant therapy to reduce risk of recurrence but may also be used for treatment in more advanced breast cancers. Selective Estrogen Receptor Modulators (SERMs) and Aromatase Inhibitors (AIs) are two main classes of hormonal drugs used for breast cancer. Both SERMs and AIs are used to treat estrogen receptor positive (ER+) breast cancer. SERMs are selective estrogen-receptor modulators, or drugs that block the naturally circulating estrogen in breast tissues and other estrogen-sensitive tissues in your body. SERMs are called "selective" because they bind to particular estrogen receptors. This selective binding action is sometimes called estrogen inhibition, or estrogen suppression. SERMs do not prevent the production of estrogen, but they help to slow or stop the growth of estrogen-sensitive cancer cells by starving them of a full dose of natural estrogen. Tamoxifen was the first SERM produced, and has been in use for over 30 years. Initially, it was used in metastatic disease, but we now know that it is effective in reducing recurrence of primary breast cancer and improving overall survival in both postmenopausal and premenopausal women. It has also been shown to reduce the incidence of recurrence of breast cancer in the contralateral breast. Tamoxifen is prescribed for 5 years and there are now studies looking at the use of tamoxifen for even longer periods of time. More recently, tamoxifen has been approved in the United States as a prevention strategy for women at high risk for developing breast cancer. However, it does have side effects. The most serious side effects are blood clots, stroke, uterine cancer and cataracts. The most common side effects are hot flashes and vaginal dryness. Aromatase Inhibitors have a different mechanism of action than SERMs. AIs prevent estrogen production instead of blocking estrogen receptors the way SERMs do. AIs reduce the amount of estrogen in the body. AIs do not block estrogen production by the ovaries, but they can block other tissues from making this hormone. That is why AIs are used in women who are in menopause, when the ovaries are no longer producing estrogen. AIs may be used as a first-line therapy or after treatment with tamoxifen. Currently, there are three AIs approved by the U.S. Food and Drug Administration: anastrazole (Arimidex), exemestane (Aromasin) and letrozole (Femara). The most serious side effect is bone thinning (osteoporosis). The most common side effects are hot flashes and body aches. For more information about the use of SERMs and AIs and about breast cancer in American Indian and Alaska Native women, please consult the articles below or contact Dr. Tillman or Ms. Myers at Phoenix Indian Medical Center. Laura.Tillman@ihs.gov; Shannon.Myers@ihs.gov. Carpenter R. Choosing early adjuvant therapy for postmenopausal women with hormone-sensitive breast cancer: aromatase inhibitors versus tamoxifen. Eur J Surg Oncol. 2008 Jul;34(7):746-55. Epub 2008 Mar 4. http://www.ncbi.nlm.nih.gov/pubmed/18296017 Buijs C, de Vries EG, Mourits MJ, Willemse PH. The influence of endocrine treatments for breast cancer on health-related quality of life. Cancer Treat Rev. 2008 Nov;34(7):640-55. Epub 2008 Jun 2. http://www.ncbi.nlm.nih.gov/pubmed/18514425 Breast International Group (BIG) 1-98 Collaborative Group, Thürlimann B, Keshaviah A, Coates AS, Mouridsen H, Mauriac L, et al. A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N Engl J Med. 2005 Dec 29;353(26):2747-57. http://www.ncbi.nlm.nih.gov/pubmed/16382061 Wingo PA, King J, Swan J, Coughlin SS, Kaur JS, Erb-Alvarez JA, Jackson-Thompson J, Arambula Solomon TG. Breast cancer incidence among American Indian and Alaska Native women: US, 1999-2004. Cancer. 2008 Sep 1;113(5 Suppl):1191-202. http://www.ncbi.nlm.nih.gov/pubmed/18720389 Tillman L, Myers S, Pockaj B, Perry C, Bay RC, Al-kasspooles M. Breast cancer in Native American women treated at an urban-based Indian health referral center 1982-2003. Am J Surg. 2005 Dec;190(6):895-902. http://www.ncbi.nlm.nih.gov/pubmed/16307942 Flum DR, Stuart S, Wilcox M. Processes and outcomes of care among Navajo women with breast cancer. JAMA. 2003 Oct 15;290(15):1996-7. http://www.ncbi.nlm.nih.gov/pubmed/14559952 Free Full Text: http://jama.ama-assn.org/cgi/content/full/290/15/1996-a MedScape CME: Comprehensive Breast Care: An Update for the Menopause Practitioner http://www.medscape.com/viewprogram/17686 Back to top Abstract of the Month \| From Your Colleagues \| Hot Topics \| Features Contents Summary ‹ Previous \| Next › From Your Colleagues OB/GYN Jean Howe, MD, MPH is the Obstetrics and Gynecology Chief Clinical Consultant (OB/GYN C.C.C.). Dr. Howe is very interested in establishing a dialogue and/or networking with anyone involved in women's health or maternal child health, especially as it applies to American Indian and Alaska Native women and also indigenous peoples around the world. Please don't hesitate to contact her by e-mail (jean.howe@ihs.gov) or phone at (928) 674-7422.