Megan Madsen, DO

According to the National Cancer Institute, 1 in 8 women will receive a diagnosis of breast cancer during their lifetime, making it the most common nonskin cancer in females. It is a disease associated with significant physical and psychological morbidity and mortality. Breast cancer carries with it a yearly mortality rate of approximately 20-30 women per 100,000, with a median age at death of 61 years. The most affected subpopulation is postmenopausal African American females.

Updated draft guidelines

In primary care, our focus has long been directed at the detection of these cancers in the earliest possible stage using mammography with the ultimate goal of decreasing mortality. Historically, less emphasis has been placed on preventing the development of the disease. As the priorities of our health care system continue to evolve, the United States Preventive Services Task Force (USPSTF) has reviewed the available evidence and updated, in draft form available for public comment, their recommendations regarding breast cancer prevention with the use of tamoxifen and raloxifene, which are two selective estrogen-receptor modulators (SERMs).

These medications have been approved by the Food and Drug Administration to reduce the risk of development of breast cancers, specifically hormone receptor–positive disease. The USPSTF has reviewed seven large randomized controlled trials evaluating women without preexisting breast cancer. Typical dosing included tamoxifen 20 mg and raloxifene 60 mg daily for a period of 5 years. Overall, these studies have shown that SERMs can be utilized to decrease the incidence of invasive breast cancer in postmenopausal women by 30%-55%, which is equal to 7 to 9 fewer events per 1,000 in a 5-year period. Tamoxifen may have similar benefits in premenopausal women. When the effectiveness of these two medications was compared head-to-head, 25% more women receiving raloxifen than those receiving tamoxifen developed invasive breast cancer (5 events per 1,000 women). For all studies, the benefits were only observed with women who had a higher calculated risk of breast cancer development. Neither medication significantly reduced the risk of estrogen receptor–negative or noninvasive breast cancer. Both medications reduced the incidence of osteoporotic fractures.

Adverse effects of SERMs

Importantly, these medications are not without potential adverse effects. Studies have shown that SERMs increase the risk for venous thromboembolic events (VTEs) such as deep-venous thrombosis or stroke by approximately 60%-90%, which is equivalent to an increase of 4 to 7 VTEs per 1,000 women over 5 years, with tamoxifen bestowing a slightly increased rate over raloxifene. Therefore, they are not recommended for use in women with a prior VTE. Tamoxifen has also been implicated in a small, potential increased incidence of endometrial cancer, specifically in women older than age 50 without a history of hysterectomy.

Other potential issues, including ischemic stroke and cataract development, have a less clearly defined risk profile. Vasomotor side effects similar to postmenopausal hot flashes are relatively common with SERM use, and although not life-threatening, can have a serious negative impact on quality of life. Physicians should weigh the potential benefits with the potential risks of taking these medications, taking into account a woman’s age, comorbidities, presence or absence of a uterus, and potential additive risks for thromboembolic events. The risk of adverse effects can be minimized when patients are selected on an individualized basis, highlighting the necessity and importance of a discussion between patient and physician before implementing preventive therapy.

Patient selection for SERM therapy

From these data, it appears that women with an increased baseline risk of developing breast cancer seem to benefit the most from preventive SERM therapy. Tools exist to help calculate the estimated risk in certain populations. One such is the National Cancer Institute Breast Cancer Risk Assessment Tool, available online at www.cancer.gov/bcrisktool/. For women older than 35 years for whom BRCA1 or BRCA2 mutation status is unknown, this calculator utilizes ethnicity, age at menarche, age at birth of first child, family history of disease prior to age 50 years in first-degree female relatives, and history of prior breast mass or biopsy to estimate a projected 5-year incidence of disease. Women with a calculated 5-year breast cancer risk of 3% or greater, who do not have increased antithrombotic risk, appear to have the most favorable risk-benefit ratio for preventive SERM therapy.

The bottom line

Breast cancer is a common disease that can have devastating physical and emotional consequences and affects an estimated 12.4% of women during their lifetime. The USPSTF has drafted an update, currently available for public comment, of its recommendations regarding the use of SERMs as preventive therapy for specific populations of women aged 40-70 years with a calculated 5-year risk of 3% or greater for future development of breast cancer. The USPSTF gives class B recommendations that physicians should engage in a dialogue with patients, assisting individuals to weigh the possible adverse drug effects with the potential reduction of breast cancer risk when these medications are utilized. The USPSTF concludes with moderate certainty that women with increased calculated risk can benefit from SERM therapy to reduce the incidence of invasive hormone receptor–positive breast cancer.

References

• U.S. Preventive Services Task Force. Medications for Risk Reduction of Primary Breast Cancer in Women: Draft Recommendation Statement. AHRQ Publication No. 13-05189-EF-2.

• Nelson HD, et al. Use of Medications to Reduce Risk for Primary Breast Cancer: A Systematic Review for the U.S. Preventive Services Task Force. Ann. Intern. Med. 2013;158:604-14.

Dr. Skolnik is associate director of the family medicine residency program at Abington (Pa.) Memorial Hospital and professor of family and community medicine at Temple University, Philadelphia. Dr. Madsen is currently a third-year resident and chief resident in the family medicine residency program at Abington Memorial Hospital.

According to the National Cancer Institute, 1 in 8 women will receive a diagnosis of breast cancer during their lifetime, making it the most common nonskin cancer in females. It is a disease associated with significant physical and psychological morbidity and mortality. Breast cancer carries with it a yearly mortality rate of approximately 20-30 women per 100,000, with a median age at death of 61 years. The most affected subpopulation is postmenopausal African American females.

Updated draft guidelines

In primary care, our focus has long been directed at the detection of these cancers in the earliest possible stage using mammography with the ultimate goal of decreasing mortality. Historically, less emphasis has been placed on preventing the development of the disease. As the priorities of our health care system continue to evolve, the United States Preventive Services Task Force (USPSTF) has reviewed the available evidence and updated, in draft form available for public comment, their recommendations regarding breast cancer prevention with the use of tamoxifen and raloxifene, which are two selective estrogen-receptor modulators (SERMs).

These medications have been approved by the Food and Drug Administration to reduce the risk of development of breast cancers, specifically hormone receptor–positive disease. The USPSTF has reviewed seven large randomized controlled trials evaluating women without preexisting breast cancer. Typical dosing included tamoxifen 20 mg and raloxifene 60 mg daily for a period of 5 years. Overall, these studies have shown that SERMs can be utilized to decrease the incidence of invasive breast cancer in postmenopausal women by 30%-55%, which is equal to 7 to 9 fewer events per 1,000 in a 5-year period. Tamoxifen may have similar benefits in premenopausal women. When the effectiveness of these two medications was compared head-to-head, 25% more women receiving raloxifen than those receiving tamoxifen developed invasive breast cancer (5 events per 1,000 women). For all studies, the benefits were only observed with women who had a higher calculated risk of breast cancer development. Neither medication significantly reduced the risk of estrogen receptor–negative or noninvasive breast cancer. Both medications reduced the incidence of osteoporotic fractures.

Adverse effects of SERMs

Importantly, these medications are not without potential adverse effects. Studies have shown that SERMs increase the risk for venous thromboembolic events (VTEs) such as deep-venous thrombosis or stroke by approximately 60%-90%, which is equivalent to an increase of 4 to 7 VTEs per 1,000 women over 5 years, with tamoxifen bestowing a slightly increased rate over raloxifene. Therefore, they are not recommended for use in women with a prior VTE. Tamoxifen has also been implicated in a small, potential increased incidence of endometrial cancer, specifically in women older than age 50 without a history of hysterectomy.

Other potential issues, including ischemic stroke and cataract development, have a less clearly defined risk profile. Vasomotor side effects similar to postmenopausal hot flashes are relatively common with SERM use, and although not life-threatening, can have a serious negative impact on quality of life. Physicians should weigh the potential benefits with the potential risks of taking these medications, taking into account a woman’s age, comorbidities, presence or absence of a uterus, and potential additive risks for thromboembolic events. The risk of adverse effects can be minimized when patients are selected on an individualized basis, highlighting the necessity and importance of a discussion between patient and physician before implementing preventive therapy.

Patient selection for SERM therapy

From these data, it appears that women with an increased baseline risk of developing breast cancer seem to benefit the most from preventive SERM therapy. Tools exist to help calculate the estimated risk in certain populations. One such is the National Cancer Institute Breast Cancer Risk Assessment Tool, available online at www.cancer.gov/bcrisktool/. For women older than 35 years for whom BRCA1 or BRCA2 mutation status is unknown, this calculator utilizes ethnicity, age at menarche, age at birth of first child, family history of disease prior to age 50 years in first-degree female relatives, and history of prior breast mass or biopsy to estimate a projected 5-year incidence of disease. Women with a calculated 5-year breast cancer risk of 3% or greater, who do not have increased antithrombotic risk, appear to have the most favorable risk-benefit ratio for preventive SERM therapy.

The bottom line

Breast cancer is a common disease that can have devastating physical and emotional consequences and affects an estimated 12.4% of women during their lifetime. The USPSTF has drafted an update, currently available for public comment, of its recommendations regarding the use of SERMs as preventive therapy for specific populations of women aged 40-70 years with a calculated 5-year risk of 3% or greater for future development of breast cancer. The USPSTF gives class B recommendations that physicians should engage in a dialogue with patients, assisting individuals to weigh the possible adverse drug effects with the potential reduction of breast cancer risk when these medications are utilized. The USPSTF concludes with moderate certainty that women with increased calculated risk can benefit from SERM therapy to reduce the incidence of invasive hormone receptor–positive breast cancer.

References

• U.S. Preventive Services Task Force. Medications for Risk Reduction of Primary Breast Cancer in Women: Draft Recommendation Statement. AHRQ Publication No. 13-05189-EF-2.

• Nelson HD, et al. Use of Medications to Reduce Risk for Primary Breast Cancer: A Systematic Review for the U.S. Preventive Services Task Force. Ann. Intern. Med. 2013;158:604-14.

Dr. Skolnik is associate director of the family medicine residency program at Abington (Pa.) Memorial Hospital and professor of family and community medicine at Temple University, Philadelphia. Dr. Madsen is currently a third-year resident and chief resident in the family medicine residency program at Abington Memorial Hospital.

According to the National Cancer Institute, 1 in 8 women will receive a diagnosis of breast cancer during their lifetime, making it the most common nonskin cancer in females. It is a disease associated with significant physical and psychological morbidity and mortality. Breast cancer carries with it a yearly mortality rate of approximately 20-30 women per 100,000, with a median age at death of 61 years. The most affected subpopulation is postmenopausal African American females.

Updated draft guidelines

In primary care, our focus has long been directed at the detection of these cancers in the earliest possible stage using mammography with the ultimate goal of decreasing mortality. Historically, less emphasis has been placed on preventing the development of the disease. As the priorities of our health care system continue to evolve, the United States Preventive Services Task Force (USPSTF) has reviewed the available evidence and updated, in draft form available for public comment, their recommendations regarding breast cancer prevention with the use of tamoxifen and raloxifene, which are two selective estrogen-receptor modulators (SERMs).

These medications have been approved by the Food and Drug Administration to reduce the risk of development of breast cancers, specifically hormone receptor–positive disease. The USPSTF has reviewed seven large randomized controlled trials evaluating women without preexisting breast cancer. Typical dosing included tamoxifen 20 mg and raloxifene 60 mg daily for a period of 5 years. Overall, these studies have shown that SERMs can be utilized to decrease the incidence of invasive breast cancer in postmenopausal women by 30%-55%, which is equal to 7 to 9 fewer events per 1,000 in a 5-year period. Tamoxifen may have similar benefits in premenopausal women. When the effectiveness of these two medications was compared head-to-head, 25% more women receiving raloxifen than those receiving tamoxifen developed invasive breast cancer (5 events per 1,000 women). For all studies, the benefits were only observed with women who had a higher calculated risk of breast cancer development. Neither medication significantly reduced the risk of estrogen receptor–negative or noninvasive breast cancer. Both medications reduced the incidence of osteoporotic fractures.

Adverse effects of SERMs

Importantly, these medications are not without potential adverse effects. Studies have shown that SERMs increase the risk for venous thromboembolic events (VTEs) such as deep-venous thrombosis or stroke by approximately 60%-90%, which is equivalent to an increase of 4 to 7 VTEs per 1,000 women over 5 years, with tamoxifen bestowing a slightly increased rate over raloxifene. Therefore, they are not recommended for use in women with a prior VTE. Tamoxifen has also been implicated in a small, potential increased incidence of endometrial cancer, specifically in women older than age 50 without a history of hysterectomy.

Other potential issues, including ischemic stroke and cataract development, have a less clearly defined risk profile. Vasomotor side effects similar to postmenopausal hot flashes are relatively common with SERM use, and although not life-threatening, can have a serious negative impact on quality of life. Physicians should weigh the potential benefits with the potential risks of taking these medications, taking into account a woman’s age, comorbidities, presence or absence of a uterus, and potential additive risks for thromboembolic events. The risk of adverse effects can be minimized when patients are selected on an individualized basis, highlighting the necessity and importance of a discussion between patient and physician before implementing preventive therapy.

Patient selection for SERM therapy

From these data, it appears that women with an increased baseline risk of developing breast cancer seem to benefit the most from preventive SERM therapy. Tools exist to help calculate the estimated risk in certain populations. One such is the National Cancer Institute Breast Cancer Risk Assessment Tool, available online at www.cancer.gov/bcrisktool/. For women older than 35 years for whom BRCA1 or BRCA2 mutation status is unknown, this calculator utilizes ethnicity, age at menarche, age at birth of first child, family history of disease prior to age 50 years in first-degree female relatives, and history of prior breast mass or biopsy to estimate a projected 5-year incidence of disease. Women with a calculated 5-year breast cancer risk of 3% or greater, who do not have increased antithrombotic risk, appear to have the most favorable risk-benefit ratio for preventive SERM therapy.

The bottom line

Breast cancer is a common disease that can have devastating physical and emotional consequences and affects an estimated 12.4% of women during their lifetime. The USPSTF has drafted an update, currently available for public comment, of its recommendations regarding the use of SERMs as preventive therapy for specific populations of women aged 40-70 years with a calculated 5-year risk of 3% or greater for future development of breast cancer. The USPSTF gives class B recommendations that physicians should engage in a dialogue with patients, assisting individuals to weigh the possible adverse drug effects with the potential reduction of breast cancer risk when these medications are utilized. The USPSTF concludes with moderate certainty that women with increased calculated risk can benefit from SERM therapy to reduce the incidence of invasive hormone receptor–positive breast cancer.

References

• U.S. Preventive Services Task Force. Medications for Risk Reduction of Primary Breast Cancer in Women: Draft Recommendation Statement. AHRQ Publication No. 13-05189-EF-2.

• Nelson HD, et al. Use of Medications to Reduce Risk for Primary Breast Cancer: A Systematic Review for the U.S. Preventive Services Task Force. Ann. Intern. Med. 2013;158:604-14.

Dr. Skolnik is associate director of the family medicine residency program at Abington (Pa.) Memorial Hospital and professor of family and community medicine at Temple University, Philadelphia. Dr. Madsen is currently a third-year resident and chief resident in the family medicine residency program at Abington Memorial Hospital.