The aim of this study was to assess the acceptability and feasibility of offering risk-based breast cancer screening and its integration into regular clinical practice. A single-arm proof-of-concept trial was conducted with a sample of 387 women aged 40–50 years residing in the city of Lleida (Spain). The study intervention consisted of breast cancer risk estimation, risk communication and screening recommendations, and a follow-up. A polygenic risk score with 83 single nucleotide polymorphisms was used to update the Breast Cancer Surveillance Consortium risk model and estimate the 5-year absolute risk of breast cancer. The women expressed a positive attitude towards varying the frequency of breast screening according to individual risk and, especially, more frequently inviting women at higher-than-average risk. A lower intensity screening for women at lower risk was not as welcome, although half of the participants would accept it. Knowledge of the benefits and harms of breast screening was low, especially with regard to false positives and overdiagnosis. The women expressed a high understanding of individual risk and screening recommendations. The participants’ intention to participate in risk-based screening and satisfaction at 1-year were very high.

From January 2019 to February 2021, 387 women aged 40 to 50 years were enrolled in the study. Potential participants were the 2038 women living in the “Primer de Maig” Basic Health Area in Lleida, Catalonia, on 31 December 2018, who would have turned between 40 to 50 years of age during the following 1.5 years. Accrual was suspended because of the COVID-19 pandemic in March 2020 when 252 women had been included and resumed in October 2020.

All women who turned 50 during the study period would have received the first invitation to participate in the population-based Breast Cancer Early Detection Program. Instead, they were invited to participate in our study. Women that declined were invited by the early detection program. From women that turned 40 to 49 years during the study period, random samples of 20 to 50 women were selected from the potential participants on a monthly basis, and the women were invited to participate until the accrual goal was achieved.

Exclusion criteria included having a previous diagnosis of breast cancer, undergoing a current breast study, or fulfilling clinical criteria for cancer-related genetic counseling. We also excluded women not understanding or speaking Catalan or Spanish or those with a physical or cognitive disability that prevented breast screening or the main outcome’s assessment.

The study intervention consisted of a baseline visit, the breast cancer risk estimation, a visit for risk communication and screening recommendations, the administration of a follow-up questionnaire, and a phone call to assess satisfaction after one year.

The baseline visit was held at the Primary Care center, where the healthcare professional provided information about the study objectives; facilitated an informative brochure about the benefits and adverse effects of breast cancer screening; obtained information on sociodemographic variables, risk factors, previous screening experience, perceived personal risk of breast cancer, and general screening knowledge, attitudes, and intentions; obtained a saliva sample to determine the genomic profile; and scheduled a screening mammogram with breast density measurement. For women that had a mammogram during the year before the first visit, breast density and presence/absence of benign lesions were obtained from that mammogram and the radiologist’s report.

Breast density was classified according to the Breast Imaging Reporting and Data System (BI-RADS), 5th edition, scoring system: almost entirely fatty (a), scattered areas of fibroglandular density (b), heterogeneously dense (c), and extremely dense (d). Mammographic findings were coded from 0 (incomplete—additional imaging needed) to 6 (known biopsy—proven malignancy). In the case of abnormal results, additional tests were requested.

Collection, conservation, and delivery of saliva samples was completed following the saliva collection protocol provided by the University of Lleida’s Proteomics and Genomics Service. Details about the genotyping process can be found in the protocol. The PRS was obtained using the 83 SNPs associated with breast cancer, based on Shieh et al.’s or Mavaddat et al.’s studies, as a composite likelihood ratio representing the individual effects of each SNP.

The primary outcome measures were attitude towards, intention to participate in, and satisfaction with personalized breast cancer screening by participating women. Attitude was measured with a three-item scale, each item ranging from 1 to 5, with higher scores indicating more positive attitudes. A “positive attitude” was defined as a total score greater than or equal to 12. Intention to participate was measured with a 5-point Likert scale from definitely will (1) to definitely will not (5). The variable was also dichotomized as intending to participate (definitely or likely) or not. Satisfaction was assessed after one year of recruitment and was measured on a 5-point Likert scale from very unsatisfied (1) to very satisfied (5). Secondary outcomes (e.g., attitude towards screening mammography, attitude towards measuring breast cancer risk, emotional impact of the measure of breast cancer risk, preference with regard to the current screening, knowledge, decisional conflict, confidence, and participation) have been detailed in full in the study protocol.

The R programming language and the RStudio environment were used for the data analysis. The Likert function of the HH package was used to obtain the graphical representation of the primary outcomes measured as Likert scales.

The R programming language and the RStudio environment.