2.3. Statistical analysis

We tested for statistical differences (P-value <0.05) of characteristics between heterozygotes and non-carriers using an ANOVA test for continuous data and Chi-square tests for categorical data. Analyses were performed with STATA (version 17.0) and R (version 4.2.2).

The LTBCR was calculated in the CanRisk tool [version 2.0]. Women were categorized in three risk groups according to the Dutch guidelines [10] by considering risk at general population level if LTBCR was under 20 %, moderate risk if LTBCR was between 20 % and 30 %, and high risk when LTBCR was above 30 %. Also, we evaluated if women would reach a LTBCR of above 50 %, as this threshold is often used in unaffected heterozygote carriers to determine eligibility for preventive surgery. In the LTBCR calculations, we included risk factors stepwise, starting with FH retrieved from the pedigree and the CHEK2 status. Risk estimation using these two variables was considered the reference, since this is currently used in clinical practice. Our main interest was to address the effect of adding information regarding the PRS₃₁₁, QRFs and BD by considering three different approaches: (1) adding PRS₃₁₁, as this information could be retrieved from the same blood sample and does not require any more information; (2) adding information that could be gathered directly from the individual during genetic testing and counselling, including PRS₃₁₁ and QRFs; and (3) adding all available information, including BD, which was available in our study for 40 heterozygotes and 18 non-carriers. Reasons for missing BD information included (1) not being able to retrieve information from the surveillance hospitals indicated in the questionnaire (n = 13); (2) being younger than 35 years at time of data collection and therefore no candidate for mammographic surveillance (n = 11); (3) eligible for participating in the Dutch population-based screening program, where we could not retrieve BD information at time of data collection (n = 14); and (4) no information on whether women were under BC surveillance or the location of BC surveillance (n = 21).