MRI Surveillance and Breast Cancer Mortality in Women With BRCA1 and BRCA2 Sequence Variations.

Importance: Magnetic resonance imaging (MRI) surveillance is offered to women with a pathogenic variant in the BRCA1 or BRCA2 gene who face a high lifetime risk of breast cancer. Surveillance with MRI is effective in downstaging breast cancers, but the association of MRI surveillance with mortality risk has not been well defined. Objective: To compare breast cancer mortality rates in women with a BRCA1 or BRCA2 sequence variation who entered an MRI surveillance program with those who did not. Design, Setting, and Participants: Women with a BRCA1 or BRCA2 sequence variation were identified from 59 participating centers in 11 countries. Participants completed a baseline questionnaire between 1995 and 2015 and a follow-up questionnaire every 2 years to document screening histories, incident cancers, and vital status. Women who had breast cancer, a screening MRI examination, or bilateral mastectomy prior to enrollment were excluded. Participants were followed up from age 30 years (or the date of the baseline questionnaire, whichever was later) until age 75 years, the last follow-up, or death from breast cancer. Data were analyzed from January 1 to July 31, 2023. Exposures: Entrance into an MRI surveillance program. Main Outcomes and Measures: Cox proportional hazards modeling was used to estimate the hazard ratios (HRs) and 95% CIs for breast cancer mortality associated with MRI surveillance compared with no MRI surveillance using a time-dependent analysis. Results: A total of 2488 women (mean [range] age at study entry 41.2 [30-69] years), with a sequence variation in the BRCA1 (n = 2004) or BRCA2 (n = 484) genes were included in the analysis. Of these participants, 1756 (70.6%) had at least 1 screening MRI examination and 732 women (29.4%) did not. After a mean follow-up of 9.2 years, 344 women (13.8%) developed breast cancer and 35 women (1.4%) died of breast cancer. The age-adjusted HRs for breast cancer mortality associated with entering an MRI surveillance program were 0.20 (95% CI, 0.10-0.43; P < .001) for women with BRCA1 sequence variations and 0.87 (95% CI, 0.10-17.25; P = .93) for women with BRCA2 sequence variations. Conclusion and Relevance: Results of this cohort study suggest that among women with a BRCA1 sequence variation, MRI surveillance was associated with a significant reduction in breast cancer mortality compared with no MRI surveillance. Further studies of women with BRCA2 sequence variations are needed to ascertain these women obtain the same benefits associated with MRI surveillance.

Clinical Considerations for the Integration of Adjuvant Olaparib into Practice for Early Breast Cancer: A Canadian Perspective.

With the recent Health Canada approval of olaparib for high-risk, HER2-negative early breast cancer, physicians are now facing the practical challenges of integrating olaparib into current management of triple-negative breast cancer (TNBC) and HR-positive, HER2-negative (HR+/HER2-) early breast cancer. This review provides perspectives on some of the challenges related to identification of olaparib candidates, with a focus on the latest guidance for germline BRCA testing and considerations regarding high-risk disease definitions. Updated treatment pathways are explored for both disease states, including other adjuvant treatment options such as pembrolizumab, capecitabine, and abemaciclib. Gaps in the current literature regarding the sequential or combined use of these adjuvant therapies are noted and future, potentially informative, studies are briefly examined.

Why do people seek out polygenic risk scores for complex disorders, and how do they understand and react to results?

We sought to explore individuals' motivations for using their direct-to-consumer genetic testing data to generate polygenic risk scores (PRSs) using a not-for-profit third-party tool, and to assess understanding of, and reaction to their results. Using a cross-sectional design, users of Impute.me who had already accessed PRS results were invited to complete an online questionnaire asking about demographics, motivations for seeking PRSs, understanding and interpretation of PRSs, and two validated scales regarding reactions to results-the Impact of Event Scale Revised (IES-R) and the Feelings About genomiC Testing Results (FACToR). Independent samples T-tests and ANOVA were used to explore associations between the variables. 227 individuals participated in the study. The most frequently reported motivation was general curiosity (98.2%). Only 25.6% of participants correctly answered all questions assessing understanding/interpretation of PRSs. Over half of participants (60.8%) experienced a negative reaction (upset, anxious, and/or sad on FACToR scale) after receiving their PRSs and 5.3% scored over the threshold for potential post-traumatic stress disorder on the IES-R. Lower understanding about PRS was associated with experiencing a negative psychological reaction (P values <0.001). Higher quality pre-test information, particularly to improve understanding, and manage expectations for PRS may be useful in limiting negative psychological reactions.