A total of 816 women were diagnosed with invasive breast cancer at 36–40 years of age in the South Swedish Health Care Region between January 1, 2000 and December 31, 2019. Out of the 403 women who had previously undergone genetic testing, 79 (19.6%) were carriers of one (or two, n = 1) pathogenic variants. The median age at breast cancer diagnosis was 38.7 (IQR 37.3–38.7) years and the median time from diagnosis to genetic analysis was 0.9 years (IQR 0.3–0.9) (Table 1).

Three hundred and fifteen women were offered an analysis of the genes ATM, BARD1, BRCA1, BRCA2, CHEK2, PALB2, RAD51C, and RAD51D. The median ages at breast cancer diagnosis and study invitation were 39.8 (IQR 38.5–39.9) and 51.5 (IQR 46.7–57.1) years, respectively. The median time from diagnosis to study invitation was 12.1 (IQR 8.3–17.9) years (Table 1).

Of the 315 invited women, 147 (46.7%) women returned the signed consent form within 4 weeks. Subsequently, 162 written reminders were sent, which resulted in an additional 47 (14.9%) consent forms being returned. Of the 194 women who accepted participation, 176 (55.9% of the entire cohort, 90.7% of the women who consented) subsequently had a blood sample drawn for DNA extraction and genetic analysis. The median turn-around time for the laboratory analysis, i.e., the time from blood sample registration to clinical report delivery, was 22 (IQR 21–24) days. Pathogenic variants were identified in 17 (9.7%) women: 6 in ATM, 1 in BARD1, 3 in BRCA1, 5 in CHEK2, and 2 in PALB2 (Supplemental 4). Variants classified as pathogenic (class 5) or likely pathogenic (class 4) are collectively called pathogenic variants in this paper.

Out of the 139 women who did not undergo genetic testing, 7 had already been tested elsewhere, 1 did not want to, 1 was too anxious to, and 1 was too ill to participate. Three women had their information letter returned (address unknown). The remaining 126 (90.6%) women did not communicate a reason for choosing not to participate.

There were no statistically significant differences between median age at breast cancer diagnosis (39.9 vs. 39.4; p = 0.26) or study invitation (51.7 vs. 51.2 years; p = 0.18) of the women who participated in the Traceback study compared with those who did not, nor was there a significant difference between median time from breast cancer diagnosis to study invitation (12.2 vs. 11.8 years; p = 0.31). In addition, when analyzing the association between participation in the Traceback study and place of residence, no significant difference was found (p = 0.55).

As compared to clinical routine, the additional tasks for the Traceback procedure consisted of registry matching and sending invitation letters, referral forms, and reminders. Between August 9, 2022 and November 10, 2022, between 10 and 40 invitation letters with referral forms were sent on a weekly basis (depending on the workload at the laboratory) and between September 1, 2022 and December 12, 2022, approximately 10–20 reminders were sent each week. This work was recorded, and a total time of 24 h was noted, corresponding to 4.6 min per invited woman or 8.2 min per woman who underwent genetic testing.

Of the 176 women who underwent genetic testing, 134 (76.1%) returned the subsequent questionnaire. Study participants’ answers to the scaled-response questions are shown as mean ± SD (Table 2). Most women, both with and without pathogenic variants, reported that they understood and were satisfied with the written study information, as well as with the opportunity for additional contacts and going through with the genetic testing. Five (4.2%) of the women with normal test results and two (14.3%) of the carriers of a pathogenic variant would have wanted additional oral information. Most women reported that they had shared the information with their relatives and that they would recommend a female friend with breast cancer to undergo genetic testing in the same way that they did.

The first open-ended question was ‘What was your experience of being offered genetic testing through a letter?’. To this question, 112 (83.6%) women had positive responses. These responses included some short answers, such as ‘Positive,’ ‘Very positive,’ ‘Good,’ ‘Very good,’ ‘Totally OK,’ and ‘Very good, grateful for the offer.’ The majority of participants wrote longer answers, such as ‘Very positive, I was immensely happy to feel that I am not forgotten.’ ‘I was very happy to get the offer, a very simple way to do the testing.’ ‘I was glad to be elected to collaborate with the investigation,’ and ‘My first thought was that it is good that doctors, researchers, etc. offer and do this type of studies on women.’ Twenty (14.9%) women reported mixed feelings, e.g., ‘I was hesitant at first, but after a discussion with my family I realized that it was only beneficial’ and ‘Exciting and scary at the same time, you both want to know and are afraid to know.’ One woman wrote that she was ‘Surprised. Made me ponder what I would want to know.’ One woman had a negative response and wrote that it was ‘A bit hard, almost shocking. Almost as hard as getting the cancer diagnosis.’

When answering the question ‘What was the main reason for choosing to participate in the study?’, 90 (67.2%) women reported only one reason. The remaining 44 women reported two (or more) reasons. In total, 71 (53.0%) women reported that they wanted increased knowledge for themselves. One woman wrote ‘I have wondered if I have any of the genes that can cause breast cancer, but I have not known how to find out if I am a carrier.’ Five women wrote that they wanted to be able to receive extended surveillance or additional interventions, such as prophylactic removal of the contralateral breast. Seventy-four (55.2%) women reported that they wanted to know more for the sake of their family members, i.e., the hereditary aspect of the disease. Illustrative quotes are ‘To know if it was hereditary, for my daughter’s sake’ and ‘That I do not have anything that I will pass on to my daughter.’ Thirty-three (24.6%) women had altruistic reasons and reported that they wanted to support medical research or help others.

Women with normal test results (n = 120) subsequently answered the question ‘What was your experience of being informed of the result from the genetic analysis through a letter?’. One hundred and twelve (93.3%) women had positive responses, such as ‘It was good, then you can read it many times’, ‘I was very happy to receive the negative result in a letter’, and ‘It felt natural since the study information was delivered by mail.’ Six women reported mixed feelings, e.g., ‘Totally OK. A bit nervous to open it in the beginning, but when I read the result then it was only joy.’ One woman wrote that she thought it was hard and one woman answered that she had not received the result. Women with pathogenic variants (n = 14) answered the question ‘What was your experience of being informed of the result from the genetic analysis through a telephone call and subsequent genetic counseling?.’ Ten (71.4%) women had a positive answer, such as ‘I think it worked well. The physician was distinct, and it felt like he took the time to answer our questions.’ and ‘Good. I got a long and informative talk that gave room for questions. Pertinent information.’ Two women expressed criticism regarding the counseling process, with differing views: ‘I think it would be better to get the result by mail and not a telephone call, but maybe you would want to talk with someone after you have read the letter’ and ‘Not so good. I wanted to have a physical meeting instead. I think that it will be better, will be less misunderstandings.’ Two women reported that they felt shocked and sad about the genetic test result.

At the end of the questionnaire, 54 (40.3%) women wrote additional comments, such as being thankful (n = 42), being supportive of the study (n = 9), or feeling happy or safe (n = 3). Furthermore, three women wrote that they would have wanted to get the offer of genetic testing earlier, i.e., not years after their initial breast cancer diagnosis.