Breast cancer polygenic risk scores: A 12-month prospective study of patient reported outcomes and risk management behavior.

Introduction: Polygenic risk scores (PRS) for breast cancer risk have emerged as a potential tool for informing disease risk management. However, little is known about women's responses to receiving this information. This study aimed to prospectively assess patient reported outcomes and risk management behavior of women choosing to receive (receivers) or decline (decliners) their breast cancer PRS. Method(s): Women either unaffected or affected by breast cancer and from families with no identified pathogenic variant in a breast cancer risk gene were invited to receive their PRS. Genotyping for 62 common variants was performed, from which a PRS and relative risk were calculated. All participants completed a questionnaire at study enrollment. Receivers completed questionnaires at two-weeks and 12- months after receiving their PRS, and decliners a second questionnaire at 12-months post study enrollment. Result(s): Of the 208 participants, 165 (79%) received their PRS. Among receivers there were no changes in anxiety or distress following testing. Receiving a low PRS was associated with reduced perceived breast cancer risk at 12-months (p = 0.030). At 12-months, breast screening and uptake of risk-reducing strategies were consistent with current Australian guidelines of breast cancer risk management. Compared to receivers, decliners reported significantly higher decisional regret regarding receipt of their PRS (p<0.001). Reasons for declining PRS included being unable to attend the appointment in person and concerns over potential emotional response. Conclusion(s): Our findings provide additional support for the suitability of PRS in clinical practice, while highlighting the issues that need to be addressed when providing this information.