P. Hall (Stockholm, So, Sweden)
Karolinska InstitutetAuthor Of 2 Presentations
74P - Identification of Women at High Risk of Breast Cancer Who Need Supplemental Screening
Abstract
Background
Mammography screening reduces breast cancer mortality by 20-40%, but a large proportion of breast cancers are detected at later stages or as interval cancers. The KARMA model was developed that identifies women who are likely to be diagnosed with breast cancer before or at the next mammography screen.
Methods
The study was based on the prospective screening cohort KARMA including 70,877 participants. The study included 974 incident cancers and 9,376 healthy individuals from the cohort. We developed an image-based risk score based on mammographic features (density, masses, microcalcifications), their left-right asymmetries, and age. A lifestyle extended score also included menopausal status, family history of breast cancer, body-mass-index, hormone replacement therapy, and use of tobacco and alcohol. A genetic extended score was also developed including a polygenic risk score including 313 single nucleotide polymorphisms in addition to the image and lifestyle factors. Relative risks were estimated using logistic regression. Tumor sub-type specific risks were also estimated. Absolute risks were estimated based on relative risks, national incidence rates, and competing mortality risk.
Results
The image-based model area under the curve (AUC) was 0.73 (95% CI 0.71,0.74). The lifestyle and genetic extended model AUCs were 0.74 (95% CI 0.72,0,75) and 0.77 (95% CI 0.75,0.79) respectively. There was a relative 8-fold difference in risk between the women at high and general risk. High risk women were more likely diagnosed with large tumors. The image-based model was validated in two external cohorts.
Conclusions
Three mammographic features and their left-right asymmetries generated the basis of the model. The model could optionally be extended with lifestyle factors, family history, and a polygenic risk score. The models identified women at high likelihood of being diagnosed with breast cancer within two years of a negative screen who possibly are in need of supplemental screening or preventive intervention.
Legal entity responsible for the study
Karolinska Institutet.
Funding
Hans and Märit Rausing.
Disclosure
All authors have declared no conflicts of interest.
75P - Use of Low-dose Tamoxifen to Improve Mammographic Screening Sensitivity in Premenopausal Women
Abstract
Background
High mammographic density decreases the sensitivity of mammography. Tamoxifen reduces mammographic density and could therefore increase the sensitivity of a mammogram. We tested if low-dose tamoxifen could be used to increase the sensitivity of mammography in premenopausal women.
Methods
The study was based on the KARMA prospective screening cohort including 28,282 premenopausal women and 517 incident breast cancers. Mammographic density was measured as percent density and as a computerized BI-RADS score using the STRATUS tool. Mammographic density-dependent screening sensitivities and tumor sizes were estimated in each of the four BI-RADS categories (A, B, C, D). The 2.5 mg tamoxifen arm of the KARISMA tamoxifen six-month trial was used to define the change of mammographic density that we would observe in KARMA, if the women were exposed to low-dose tamoxifen for 6 months. Screening sensitivities and tumor sizes were predicted in the KARMA cohort assuming all women were exposed to 2.5 mg of tamoxifen. Reduction in interval and advanced cancers were estimated in women with relative mammographic density decreases from 10% to 50%.
Results
During the 8-year follow-up, 287 (56%) screening-detected and 230 (44%) interval cancers were diagnosed in the KARMA cohort. The screening sensitivities before exposure to tamoxifen were 77%, 69%, 53%, 46% for the BI-RADS categories A, B, C and D. The mean density decrease after exposure to 2.5 mg of tamoxifen was 15.4% and the BI-RADS category-dependent change in sensitivity was 0% (p=0.95), 2% (p=0.01), 4% (p<0.001), and 5% (p<0.001), respectively. A density decrease of ≥20% reduced the number of interval cancers by 24% (p<0.01) and the probability of identifying >20 mm tumors by 4% (p<0.01).
Conclusions
Low-dose tamoxifen has the potential to increase the sensitivity of a screening mammogram and therefore reduce the proportion of interval and advanced cancers in mammography screening.
Legal entity responsible for the study
Hans and Märit Raussing, Kamprad Foundation.
Funding
Hans and Märit Raussing, Kamprad Foundation.
Disclosure
All authors have declared no conflicts of interest.