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Validated quantitative models are available that permit the accurate estimation of a woman's risk of developing invasive breast cancer during a specified period of time. Data from the National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial indicate that tamoxifen can reduce the risk of developing breast cancer by at least 49% in women who are at increased risk. All premenopausal women whose 5-year risk of developing breast cancer is 1.67% or greater derive a net benefit from taking tamoxifen for risk reduction. Women who have either lobular carcinoma-in-situ or atypical ductal or lobular hyperplasia derive an even greater net benefit. Women who carry mutations in either the BRCA1 or BRCA2 gene will also experience reduced incidence of breast cancer with tamoxifen. Although postmenopausal women derive a net benefit from tamoxifen through the reduction of both breast cancer and bone fracture event rates, the risks of both invasive endometrial cancer and thromboembolic events must be balanced in older women. Physicians should identify appropriate candidates with whom to discuss the possible benefits of tamoxifen for reducing the risk of breast cancer.

At the time of the release of the findings of the Breast Cancer Prevention Trial (BCPT), early interim results from two smaller European studies were also released. These smaller studies included one from the Royal Marsden (RM) Hospital in London, England, and another from the Italian National Cancer Institute. Since then, there has been much discussion about the relevance of the interim findings from the European studies and the likely reason for the failure of these studies to find a treatment effect. In some instances, the discussion has been incomplete or inconsistent with the observations from the trial. This has caused some confusion regarding the likely differences among the three studies of breast cancer prevention with tamoxifen. Recently, investigators from the RM study have published their interpretation of the reasons for the negative findings from the European studies. The discussions of the RM investigators are reviewed and used as a basis to illustrate some misconceptions regarding key differences in trial design and implementation among the BCPT and the European trials. The investigator discussions are also used to illustrate the significance of performing an appropriate benefit/risk assessment to identify women who would likely have a net beneficial effect when using tamoxifen to reduce the risk of breast cancer occurrence. Differences in terms of the characteristics of the study populations resulting in inadequate statistical power is the most likely reason for the failure to detect treatment differences in the European trials. Possible confounding due to the use of hormone replacement therapy is another reason that must be considered. Also, benefit/risk analysis indicates that tamoxifen has substantial public health potential as an approach to reduce breast cancer incidence and the physical and mental morbidity associated with this disease. The drug cannot be used indiscriminately due to the potential side effects, but benefit/risk assessment methodology can be used to identify substantial numbers of women in whom treatment would provide a net beneficial effect.

Background: In response to findings from the Breast Cancer Prevention Trial that tamoxifen treatment produced a 49% reduction in the risk of invasive breast cancer in a population of women at elevated risk, the National Cancer Institute sponsored a workshop on July 7 and 8, 1998, to develop information to assist in counseling and in weighing the risks and benefits of tamoxifen. Our study was undertaken to develop tools to identify women for whom the benefits outweigh the risks., Methods: Information was reviewed on the incidence of invasive breast cancer and of in situ lesions, as well as on several other health outcomes, in the absence of tamoxifen treatment. Data on the effects of tamoxifen on these outcomes were also reviewed, and methods were developed to compare the risks and benefits of tamoxifen., Results: The risks and benefits of tamoxifen depend on age and race, as well as on a woman's specific risk factors for breast cancer. In particular, the absolute risks from tamoxifen of endometrial cancer, stroke, pulmonary embolism, and deep vein thrombosis increase with age, and these absolute risks differ between white and black women, as does the protective effect of tamoxifen on fractures. Tables and aids are developed to describe the risks and benefits of tamoxifen and to identify classes of women for whom the benefits outweigh the risks., Conclusions: Tamoxifen is most beneficial for younger women with an elevated risk of breast cancer. The quantitative analyses presented can assist health care providers and women in weighing the risks and benefits of tamoxifen for reducing breast cancer risk.

Background: The finding of a decrease in contralateral breast cancer incidence following tamoxifen administration for adjuvant therapy led to the concept that the drug might play a role in breast cancer prevention. To test this hypothesis, the National Surgical Adjuvant Breast and Bowel Project initiated the Breast Cancer Prevention Trial (P-1) in 1992., Methods: Women (N=13388) at increased risk for breast cancer because they 1) were 60 years of age or older, 2) were 35-59 years of age with a 5-year predicted risk for breast cancer of at least 1.66%, or 3) had a history of lobular carcinoma in situ were randomly assigned to receive placebo (n=6707) or 20 mg/day tamoxifen (n=6681) for 5 years. Gail's algorithm, based on a multivariate logistic regression model using combinations of risk factors, was used to estimate the probability (risk) of occurrence of breast cancer over time., Results: Tamoxifen reduced the risk of invasive breast cancer by 49% (two-sided P<.00001), with cumulative incidence through 69 months of follow-up of 43.4 versus 22.0 per 1000 women in the placebo and tamoxifen groups, respectively. The decreased risk occurred in women aged 49 years or younger (44%), 50-59 years (51%), and 60 years or older (55%); risk was also reduced in women with a history of lobular carcinoma in situ (56%) or atypical hyperplasia (86%) and in those with any category of predicted 5-year risk. Tamoxifen reduced the risk of noninvasive breast cancer by 50% (two-sided P<.002). Tamoxifen reduced the occurrence of estrogen receptor-positive tumors by 69%, but no difference in the occurrence of estrogen receptor-negative tumors was seen. Tamoxifen administration did not alter the average annual rate of ischemic heart disease; however, a reduction in hip, radius (Colles'), and spine fractures was observed. The rate of endometrial cancer was increased in the tamoxifen group (risk ratio = 2.53; 95% confidence interval = 1.35-4.97); this increased risk occurred predominantly in women aged 50 years or older. All endometrial cancers in the tamoxifen group were stage I (localized disease); no endometrial cancer deaths have occurred in this group. No liver cancers or increase in colon, rectal, ovarian, or other tumors was observed in the tamoxifen group. The rates of stroke, pulmonary embolism, and deep-vein thrombosis were elevated in the tamoxifen group; these events occurred more frequently in women aged 50 years or older., Conclusions: Tamoxifen decreases the incidence of invasive and noninvasive breast cancer. Despite side effects resulting from administration of tamoxifen, its use as a breast cancer preventive agent is appropriate in many women at increased risk for the disease.

Background: The purpose of this study was to evaluate the effect of physician recommendation on whether to enroll in a randomized controlled chemoprevention trial for breast cancer., Methods: We surveyed 360 women who were at increased risk for breast cancer regarding social and behavioral factors that could influence their decision to enroll or not to enroll in the Breast Cancer Prevention Trial (BCPT). Respondents completed a questionnaire following attendance at an informational session about the trial. The analysis was restricted to 175 women who discussed the possibility of their participation in the trial with their primary care physician (PCP) and who reported what their physician advised them to do regarding participation., Results: Logistic regression modeling showed that among women who discussed the trial with their physician, physician recommendation was the most important factor that influenced the respondent's decision to enroll in the BCPT. Women who reported that their physician advised them to enroll in the trial were 13 times more likely to participate than were women who reported that their physicians advised them not to participate., Conclusions: The results of our study show that PCPs play an important role in influencing preventive health behavior, specifically, regarding enrollment in a randomized breast cancer chemoprevention trial. Efforts to increase recruitment to a trial should include enlisting the support of PCPs., (Copyright 1998 American Health Foundation and Academic Press.)

Background: In response to findings from the Breast Cancer Prevention Trial that tamoxifen treatment produced a 49% reduction in the risk of invasive breast cancer in a population of women at elevated risk, the National Cancer Institute sponsored a workshop on July 7 and 8, 1998, to develop information to assist in counseling and in weighing the risks and benefits of tamoxifen. Our study was undertaken to develop tools to identify women for whom the benefits outweigh the risks.Methods: Information was reviewed on the incidence of invasive breast cancer and of in situ lesions, as well as on several other health outcomes, in the absence of tamoxifen treatment. Data on the effects of tamoxifen on these outcomes were also reviewed, and methods were developed to compare the risks and benefits of tamoxifen.Results: The risks and benefits of tamoxifen depend on age and race, as well as on a woman's specific risk factors for breast cancer. In particular, the absolute risks from tamoxifen of endometrial cancer, stroke, pulmonary embolism, and deep vein thrombosis increase with age, and these absolute risks differ between white and black women, as does the protective effect of tamoxifen on fractures. Tables and aids are developed to describe the risks and benefits of tamoxifen and to identify classes of women for whom the benefits outweigh the risks.Conclusions: Tamoxifen is most beneficial for younger women with an elevated risk of breast cancer. The quantitative analyses presented can assist health care providers and women in weighing the risks and benefits of tamoxifen for reducing breast cancer risk. [ABSTRACT FROM AUTHOR]

The article discusses the similar efficacy of raloxifene and tamoxifen for the prevention of invasive breast cancer in women at increased risk in postmenopausal women. Raloxifene had lower risks of uterine hyperplasia, venous thromboembolism and cataracts. The estimated probabilities of selective estrogen receptor modulator-associated benefits and risks can be weighed against a woman's risk of breast cancer as predicted by tools such as the Gail Model.

Women at increased risk for breast cancer (BC) are eligible to take selective estrogen receptor modulators (SERMs) to reduce their risk; Food and Drug Administration (FDA) approval of tamoxifen or raloxifene for BC risk reduction and American Society of Clinical Oncology (ASCO) guidelines for the use of SERMs recommend the two drugs for any woman over the age of 35 years with a 5-year risk of 1.67% or greater, but identifying those women can be both challenging and costly. We used an electronic database (Centricity RIS -IC) from the Geisinger Health System (GHS) Department of Radiology with 77,000 women ages 35-90 years to calculate 5-year and lifetime risks of developing invasive BC using National Cancer Institute's (NCI) Breast Cancer Risk Assessment Macro (BrCa RAM). BrCa RAM calculates risk based on patient age, number of biopsies, did a biopsy ever display atypical hyperplasia (Yes/No), age at menarche, age at first live birth, number of first degree relatives with breast cancer, and patient race. Demographic information (age, race, sex) was obtained from the electronic health record (EpicCare), pathology information (number of biopsies, atypical hyperplasia) was obtained from the pathology application (CoPath), and personal history (number of first degree relatives with breast cancer) were obtained from RIS. Age at menarche and age at first live birth could not be obtained, but makes a small relative contribution to the risk of BC. Sensitivity analysis explored implications of missing data; imputing ages for age at first live birth and age at menarche showed that the absence of this data did not overestimate the five-year and lifetime risks. There were 5,897 patients with calculated 5-year breast cancer risk 2; mean age was 65.8 years, mean 5-yr risk of BC = 3.05% (max 18.2%). The number of patients by 5-year risk score category were: risk 2-2.5% (n = 1728); 2.5%-3% (n = 3188); 3%+ (n = 981). There were 4,196 patients with a GHS primary care physician (PCP); 5,086 patients had seen any Geisinger physician within the past year; 4,113 women had seen their PCP in the past year. Only 239 patients ever received a prescription for tamoxifen or raloxifene, and some received raloxifene for prevention or treatment of osteoporosis and not for BC risk reduction. Only 40 were currently taking tamoxifen or raloxifene. These data from an integrated health system with an electronic health record validate the under-utilization of SERMs for primary BC risk reduction. Strategies are being designed to increase their use in GHS by using the risk score to identify the population and attempt to intervene using a risk modification clinical program. [ABSTRACT FROM AUTHOR]