Background: Selective estrogen receptor modulators (SERMs), tamoxifen and raloxifene, are FDA-approved for breast cancer (BC) risk reduction. However, uptake has been poor in the prevention setting, partly due to a lack of knowledge in the medical community about BC prevention and public misconceptions about the risks of SERMs. We assessed demographic and clinical factors that influence SERM uptake among high-risk women seen in an academic breast center, where specialized risk counseling is provided by a breast surgeon or medical oncologist. Methods: Potential subjects included high-risk women seen for an initial consultation by Breast Surgery or Medical Oncology. Eligibility for SERM use included a 5-year Gail risk ≥1.67%, lobular carcinoma in situ (LCIS), BRCA mutation carrier, or estrogen receptor (ER)-positive and/or progesterone receptor (PR)-positive ductal carcinoma in situ (DCIS). Demographic and BC risk factor data was collected from self-administered questionnaires. Clinical data, including prior/current SERM use, was abstracted from medical chart review. Differences in distribution of risk factors, between women who ever took a SERM and those who did not, were examined using chi-square statistics or Fisher's exact test. Multivariable logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals using SERM use as the dependent variable. Results: Among 247 high-risk women enrolled between March 2007 and January 2011, median age 51 (17-82); White/Hispanic/Black/Asian (%): 55/32/7/6. 85% of women were undergoing annual mammography, 94% had a breast biopsy, 19% genetic testing, and 71% Medical Oncology referral. Among 181 (73%) women eligible for a SERM, Gail risk ≥1.67%/LCIS/DCIS/BRCA mutation (%): 35/22/39/3; 83 (46%) ever took a SERM, including 62 on tamoxifen and 21 on raloxifene. Early SERM discontinuation was only 7%. In multivariable analysis, significant predictors of SERM uptake included risk category (DCIS vs. Gail risk ≥1.67%/LCIS/BRCA mutation), higher income, higher body mass index (BMI), and referral to Medical Oncology. In terms of this high-risk population meeting American Cancer Society (ACS) behavioral guidelines for cancer prevention, 53% had a BMI <25 kg/m2, 44% consumed ≤1 alcoholic beverage per day, and 10% engaged in ≥4 hours of moderate physical activity per week; only 3.5% met all 3 recommendations. Conclusions: Among high-risk women seen at a specialized breast center, application of clinical recommendations such as screening mammography, genetic testing, and SERM uptake were relatively high, suggesting that a comprehensive approach to the management of high-risk women is feasible. However, meeting ACS nutrition and physical activity guidelines for cancer prevention was limited, perhaps due to a lack of reimbursable staff to implement these guidelines. Breast cancer risk assessment and available interventions for prevention among high-risk women are underutilized in the U.S. Future studies should focus on the development and delivery of breast cancer prevention strategies. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-11-06.
Introduction: High absolute breast density and increased breast density over time are strongly associated with breast cancer risk, and breast density generally decreases with increasing age. We examined mammographic density data from members of the Women At Risk High-Risk Registry at Columbia University Medical Center (WAR), a cohort defined as at high risk for breast cancer due to family history of breast cancer, history of lobular carcinoma in situ, and/or benign breast disease, to determine changes in their breast density over time. Methods: Within the WAR cohort of 1598 women, we conducted a nested case-control study of 66 incident cases of invasive breast cancer and 70 women without cancer, matched on age and time between first and second mammogram. For each participant, we collected two mammograms (for the cases, both mammograms occurred before cancer diagnosis), to examine differences in absolute density, percent density, and change in density between cases and controls. The average time between first and second mammogram was 4.6 years for both cases and controls, with a range of between 1 and 15 years. Results: Using linear regression with change in percent density as the outcome, and time between first and second mammogram as the independent variable, we found that among women without breast cancer, density decreased as time between first and second mammogram increased (β = −2.15, p = 0.005). In contrast, there was no overall change in density among the cases associated with time between first and second mammogram (β = 0.69, p = 0.39). In an ANCOVA comparing the slopes of the regression lines, the slopes were significantly different for cases versus controls (p = 0.009). Conclusion: In a cohort of women at high risk for breast cancer, breast density does not decrease as time between mammograms increases, for women who go on to develop breast cancer. For women who do not develop breast cancer, breast density decreases significantly over time.
Background: Chemoprevention with antiestrogens, such as tamoxifen, raloxifene, and aromatase inhibitors (AIs), reduces breast cancer incidence in high-risk women. However, uptake has been poor in the prevention setting. We examined demographic and clinical factors that influenced chemoprevention uptake in women with an elevated Gail risk score (≥1.67%), lobular/ductal carcinoma in situ (LCIS/DCIS), and/or BRCA mutation carriers. Methods: We enrolled women prospectively without a diagnosis of invasive breast cancer, who were seen for an initial consultation by breast surgery or medical oncology at Columbia University Medical Center. Eligibility for chemoprevention included a 5-year Gail risk ≥1.67%, LCIS, known BRCA1 or BRCA2 mutation, or hormone receptor (HR)-positive DCIS. Demographic and risk factor data were collected from a self-administered baseline questionnaire and clinical data from medical chart review, including prior/current chemoprevention, type of antiestrogen, duration of use, and toxicities. Differences in distribution of risk factors between women who ever took chemoprevention and those who did not were examined using chi-square statistics or Fisher's exact test. We used log-binomial regression models to estimate relative risks (RRs) and 95% confidence intervals (95% CI) using chemoprevention uptake as the dependent variable. A subset of high-risk women completed questionnaires assessing their attitudes towards chemoprevention and perceived risks/benefits. Results: Among 412 women enrolled between March 2007 and April 2013, 316 (77%) were eligible for chemoprevention. Main reasons for ineligibility included 5-year Gail risk <1.67% (40%), age <35 (24%), HR-negative DCIS (17%), opting for bilateral mastectomies (11%), and medical contraindications (8%). Among those eligible for chemoprevention, median age 53 (26-88); White/Hispanic/Black/Asian/other (%): 55/29/8/7/1; risk category, 5-year Gail risk ≥1.67%/LCIS/DCIS/BRCA mutation (%): 36/22/40/2. Overall, 162 (51%) women started an antiestrogen (72% for DCIS and 37% among high-risk women), including 114 on tamoxifen, 40 on raloxifene, and 11 on an AI. Early discontinuation occurred in 27 (18%) women, but 7 switched to a different antiestrogen. In univariable analysis, postmenopausal status and medical oncology referral were associated with higher chemoprevention uptake. In multivariable analysis, only higher risk was a significant predictor of chemoprevention uptake. Among the subset of women who completed additional questionnaires on attitudes towards chemoprevention, they reported that the most important factors in chemoprevention decision-making included their healthcare provider (50%), results of chemoprevention studies (44%), and knowledge about others’ experience with chemoprevention (44%). The majority (69%) were concerned about side effects, specifically blood clots with tamoxifen and raloxifene and bone fractures with AIs. Conclusions: In high-risk women seen at an academic breast center, chemoprevention uptake was relatively high compared to the published literature. Further research is needed to determine how the risks and benefits of chemoprevention are best communicated to women to enhance informed decision-making and increase uptake of chemoprevention strategies. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-13-01.
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