Side Effects Revealed: Women’s Experiences With Aromatase Inhibitors A Report From Breast Cancer Action JANUARY 2007 Side Effects Revealed: Women’s Experiences With Aromatase Inhibitors By Marilyn T. Zivian, Ph.D., and Brenda Salgado, M.S. JANUARY 2007 A Report From 55 New Montgomery Street, Suite 323 San Francisco, CA 94105 Phone: (415) 243-9301 Toll-free: (877) 2STOPBC www.bcaction.org [email protected] Th is report is dedicated to the hundreds of women who generously took the time to respond to Breast Cancer Action’s Aromatase Inhibitor Side Eff ects Survey and to everyone who seeks to make informed decisions about the care they receive. Table of Contents Executive Summary . 1 Introduction . 3 Methods . 4 Results . 5 Conclusions . 13 Acknowledgements BCA Reviewers Survey Design Assistance Barbara Brenner Diane Tompkins, Th e Curious Company Executive Director Rebecca Farmer Graphic Design Communications Offi cer Yvonne Day, Y. Day Designs Katrina Kahl Communications Associate Printing Inkworks Press Lisa Wanzor Associate Director Breast Cancer Action wishes to thank the many women who participated in the survey and the organizations and individuals who assisted in its distribution. Th is publication and quotes from survey respondents are available online at www.bcaction.org. ©2007 Breast Cancer Action Breast Cancer Action 1 Executive Summary Aromatase inhibitors (AIs) are hormonal therapies approved for use in postmenopausal women with breast cancer. Th ree AIs have been approved by the U.S. Food and Drug Administration (FDA): anastrozole (Arimidex), exemestane (Aromasin), and letrozole (Femara). Because AIs are relatively new drugs, little information is available about their long-term side eff ects. Breast Cancer Action (BCA) is conducting a survey on the side eff ects women are experiencing while taking these drugs. Th e goal of this survey is to provide information about side eff ects to patients, doctors, the FDA, the National Cancer Institute, and other cancer organizations. About the Survey Th e AI Side Eff ects Survey was developed in 2005, and includes questions about the respondent’s age, place of residence, the AI prescribed, date started and date stopped (if applicable), purpose of prescription, whether the patient was given information by her health care provider about side eff ects and recommended duration of use, menopausal status at the time of prescription, and other treatments received for breast cancer. Th e questions are followed by a list of 38 side eff ects that was generated from FDA product information documents for the three AIs. Respondents rated the side eff ects for severity (none, mild, moderate, or severe). Finally, respondents were asked to report any additional side eff ects. Th e sample of respondents is self-selected and may not be representative of the population of women taking AIs. Th erefore, the results cannot be generalized to the larger population. Summary of Findings Th e fi rst 612 completed surveys received were analyzed for this report. Major fi ndings include: 1. Most respondents (96%) reported one or more side eff ects. 2. Th e side eff ects reported by over 50% of respondents were: hot fl ashes (65%), bone pain (64%), feeling tired (59%), muscle pain (58%), and insomnia (51%). 3. Many women reported side eff ects in addition to those on our list, including joint-related side eff ects, vaginal atrophy and dryness, a rise in cholesterol levels, and general pain. 4. Over 50% of respondents stated that their menopause was not naturally occurring. For these women, menopause was either pharmaceutically or surgically induced. 5. Ten women (1.6%) reported that they discontinued using an AI because of subsequent menstruation or vaginal bleeding. 6. About 30% of the respondents discontinued the use of an AI—84% because of side eff ects they were experiencing, and close to half of them (47%) specifi cally because of joint-related side eff ects. 7. Over one-third (37%) of respondents reported receiving no information from their doctors about short-term side eff ects; nearly two-thirds (63%) reported receiving no information from their doctors about long-term side eff ects. 2 Side Effects Revealed: Women’s Experiences With Aromatase Inhibitors Conclusions While the population of survey respondents is not necessarily representative of all women taking AIs, the initial results of our survey show that most women in our sample experienced one or more side eff ects. Many patients reported not receiving information from their doctors about the side eff ects of AIs. However, these are relatively new drugs and clinical trials rarely report on long-term side eff ects. Th us little information is available to doctors and patients about the long-term side eff ects of AIs. Aromatase inhibitors are indicated for use only in postmenopausal women with breast cancer. Based on responses, it is apparent that some women who are not postmenopausal are being prescribed AIs—either because they were thought to be postmenopausal but later resumed menstruating, or because they were premenopausal and had their ovarian function supressed.1 Th e survey results clearly suggest that patients need better information about the side eff ects of AIs and whether the use of AIs is actually appropriate for them. Recommendations 1. Conduct additional research on short-term and long-term side eff ects of AIs. 2. Provide the results of this research to doctors and patients. 3. Use caution when prescribing AIs to perimenopausal women, as well as to premenopausal women who have been rendered menopausal by chemotherapy or ovarian function suppression. 1 Th ree Phase III trials (SOFT IBCSG-24-02; TEXT IBCSG-25-02; PERCHE IBCSG-26-02) are currently looking at the use of exemestane in premenopausal women whose ovarian function has been suppressed either surgically, pharmaceutically, or through radiation of the ovaries. Th ese trials were started in 2003, and results will not be available for several years. Until these trials are completed, no data exist to support the use of AIs in women whose menopause is artifi cially induced. Breast Cancer Action 3 INTRODUCTION ntil recently, tamoxifen has been one of the primary drugs used in the treatment of breast cancer. When Uit was approved for use, little was known about its long-term side eff ects. Aft er being contacted by women reporting side eff ects they were experiencing, BCA published a series of articles on tamoxifen in its newsletter. As a result, BCA became an informal repository for women’s reports of side eff ects. Eventually breast cancer patients’ informal reports to doctors and others prompted side eff ects research that confi rmed their anecdotal experiences. Now, more than ten years later, AIs are quickly replacing tamoxifen as the drug of choice for treating hormone- responsive breast cancer in postmenopausal women. As with tamoxifen a decade ago, little is known about the long- term side eff ects of these drugs. Th is time, BCA decided to systematically collect data on the side eff ects women have been experiencing. BCA’s goals in providing this information are to enable patients to make better decisions, doctors to make more informed recommendations, and the FDA to monitor AI side eff ects. About Aromatase Inhibitors Aromatase inhibitors are a type of hormone therapy for postmenopausal women with breast cancer. AIs prevent the aromatase enzyme from converting the hormone androgen into estrogen. Produced by the adrenal gland and found throughout the body, androgen is the principal source of estrogen for postmenopausal women. AIs have only been approved for use by postmenopausal women. Th ey are ineff ective in premenopausal women whose ovaries are still producing estrogen (which is not aff ected by the aromatase enzyme). None of these drugs has been approved by the FDA for use by healthy women at high risk of developing breast cancer. Th ree AIs are currently approved by the FDA for the treatment of breast cancer in postmenopausal women: anastrozole (Arimidex), exemestane (Aromasin), and letrozole (Femara). Anastrozole and letrozole are both nonsteroidal aromatase inhibitors. Th ey are described as reversible because they bind reversibly to the aromatase enzyme. Exemestane is a steroidal inhibitor that forms an irreversible bond with the aromatase enzyme, permanently stopping the activity of the enzyme. Th ese drugs were fi rst approved for treatment of advanced breast cancer in postmenopausal women on the following dates: anastrozole in December 1995, letrozole in July 1997, and exemestane in October 1999. Th e FDA Indication and Usage for the three AIs is as follows: 1 Anastrozole (Arimidex) • Arimidex is indicated for adjuvant treatment of postmenopausal women with hormone-receptor-positive early breast cancer. • Arimidex is indicated for the fi rst-line treatment of postmenopausal women with hormone-receptor-positive or hormone-receptor-unknown locally advanced or metastatic breast cancer. • Arimidex is indicated for the treatment of advanced breast cancer in postmenopausal women with disease progression following tamoxifen therapy. 1 Th e indication and usage information for anastrozole, exemestane, and letrozole on pages 3 and 4 were taken from the FDA web site, www.fda.gov, in October 2006. 4 Side Effects Revealed: Women’s Experiences With Aromatase Inhibitors Exemestane (Aromasin) • Aromasin is indicated for adjuvant treatment of postmenopausal women with estrogen-receptor-positive early breast cancer who have received two to three years of tamoxifen and are switched to Aromasin for completion of a total of fi ve consecutive years of adjuvant hormonal therapy. • Aromasin is indicated for the treatment of advanced breast cancer in postmenopausal women whose disease has progressed following tamoxifen therapy. Letrozole (Femara) • Femara is indicated for the adjuvant treatment of postmenopausal women with hormone-receptor-positive early breast cancer. • Femara is indicated for the extended adjuvant treatment of early breast cancer in postmenopausal women who have received fi ve years of adjuvant tamoxifen therapy.