Supplemental Figure 1: The Study Schema Defines Information Collected During Each Patient Visit and at Each Follow-Up Time Point. Visit 1 consisted of a baseline breast cancer risk assessment (NCI-BCRAT and IBIS BC risk scores without PRS) and discussion of risk-reducing options, including ET, with a participating physician or nurse practitioner. During Visit 2, NCI-BCRAT and IBIS BC risk scores, with and without PRS, were presented and explained to participants, and ET risks, benefits, and potential adverse effects were discussed again. ET prescriptions were provided to those who wished to proceed. The participants completed the same survey as was completed after Visit 1. Follow-up assessments were performed 1 and 2 years after Visit 2 and evaluated QOL with the FACT-GP/ES questionnaire.
ARTICLE ABSTRACT
Refinement of breast cancer risk estimates with a polygenic-risk score (PRS) may improve uptake of risk-reducing endocrine therapy (ET). A previous clinical trial assessed the influence of adding a PRS to traditional risk estimates on ET use. We stratified participants according to PRS-refined breast cancer risk and evaluated ET use and ET-related quality of life (QOL) at 1-year (previously reported) and 2-year follow-ups. Of 151 participants, 58 (38.4%) initiated ET, and 22 (14.6%) discontinued ET by 2 years; 42 (27.8%) and 36 (23.8%) participants were using ET at 1- and 2-year follow-ups, respectively. At the 2-year follow-up, 39% of participants with a lifetime breast cancer risk of 40.1% to 100.0%, 18% with a 20.1% to 40.0% risk, and 16% with a 0.0% to 20.0% risk were taking ET (overall P = 0.01). Moreover, 40% of participants whose breast cancer risk increased by 10% or greater with addition of the PRS to a traditional breast cancer-risk model were taking ET versus 0% whose risk decreased by 10% or greater (P = 0.004). QOL was similar for participants taking or not taking ET at 1- and 2-year follow-ups, although most who discontinued ET did so because of adverse effects. However, these QOL results may have been skewed by the long interval between QOL surveys and lack of baseline QOL data. PRS-informed breast cancer prevention counseling has a lasting, but waning, effect over time. Additional follow-up studies are needed to address the effect of PRS on ET adherence, ET-related QOL, supplemental breast cancer screening, and other risk-reducing behaviors.
Risk-reducing medications for breast cancer are considerably underused. Informing women at risk with precise and individualized risk assessment tools may substantially affect the incidence of breast cancer. In our study, a risk assessment tool (IBIS-polygenic-risk score) yielded promising results, with 39% of women at highest risk starting preventive medication.
