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Background: Genetic screening for pathogenic variants (PVs) in cancer predisposition genes can affect treatment strategies, risk prediction and preventive measures for patients and families. For decades, hereditary breast and ovarian cancer (HBOC) has been attributed to PVs in the genes BRCA1 and BRCA2, and more recently other rare alleles have been firmly established as associated with a high or moderate increased risk of developing breast and/or ovarian cancer. Here, we assess the genetic variation and tumor characteristics in a large cohort of women with suspected HBOC in a clinical oncogenetic setting. Methods: Women with suspected HBOC referred from all oncogenetic clinics in Sweden over a six-year inclusion period were screened for PVs in 13 clinically relevant genes. The genetic outcome was compared with tumor characteristics and other clinical data collected from national cancer registries and hospital records. Results: In 4622 women with breast and/or ovarian cancer the overall diagnostic yield (the proportion of women carrying at least one PV) was 16.6%. BRCA1/2 PVs were found in 8.9% of women (BRCA1 5.95% and BRCA2 2.94%) and PVs in the other breast and ovarian cancer predisposition genes in 8.2%: ATM (1.58%), BARD1 (0.45%), BRIP1 (0.43%), CDH1 (0.11%), CHEK2 (3.46%), PALB2 (0.84%), PTEN (0.02%), RAD51C (0.54%), RAD51D (0.15%), STK11 (0) and TP53 (0.56%). Thus, inclusion of the 11 genes in addition to BRCA1/2 increased diagnostic yield by 7.7%. The yield was, as expected, significantly higher in certain subgroups such as younger patients, medullary breast cancer, higher Nottingham Histologic Grade, ER-negative breast cancer, triple-negative breast cancer and high grade serous ovarian cancer. Age and tumor subtype distributions differed substantially depending on genetic finding. Conclusions: This study contributes to understanding the clinical and genetic landscape of breast and ovarian cancer susceptibility. Extending clinical genetic screening from BRCA1 and BRCA2 to 13 established cancer predisposition genes almost doubles the diagnostic yield, which has implications for genetic counseling and clinical guidelines. The very low yield in the syndrome genes CDH1, PTEN and STK11 questions the usefulness of including these genes on routine gene panels. [ABSTRACT FROM AUTHOR]

Objectives: Hereditary cancer risks can be effectively managed if at-risk relatives enroll in surveillance and preventive care. Family-mediated risk disclosure has internationally been shown to be incomplete, selective and leave over a third of eligible at-risk individuals without access to genetic counseling. We explored patients handling of cancer risk information in practice., Methods: We conducted twelve semi-structured interviews with patients who had completed their genetic counseling and been asked to disclose risk information to relatives. Questions were designed to investigate lived experiences of communicating hereditary risk and focused on disclosure strategies, intrafamilial interactions and emotional responses., Results: Qualitative content analysis yielded five categories. These span personal fears, shared responsibilities, feeling of empowerment, innovative solutions and unmet needs. Patients put high value on collaboration with their genetic healthcare professionals but also solicited better overview of the counseling process and more personalized, case-tailored information., Conclusions: Our results add novel insights about the practical strategies employed by genetic counselees and their motivations behind disclosing hereditary risk information to relatives., Practice Implications: A patient-centered cancer genetics care would clarify roles and responsibilities around risk disclosure, inform counselees about the process upfront and tailor information to offer case-specific data with the family's inheritance pattern explained., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Targeted surveillance of at-risk individuals in families with increased risk of hereditary cancer is an effective prevention strategy if relatives are identified, informed and enrolled in screening programs. Despite the potential benefits, many eligible at-risk relatives remain uninformed of their cancer risk. This study describes the general public's opinion on disclosure of hereditary colorectal cancer (CRC) risk information, as well as preferences on the source and the mode of information. Methods: A random sample of the general public was assessed through a Swedish citizen web-panel. Respondents were presented with scenarios of being an at-risk relative in a family that had an estimated increased hereditary risk of CRC; either 10% (moderate) or 70% (high) lifetime risk. A colonoscopy was presented as a preventive measure. Results were analysed to identify significant differences between groups using the Pearson's chi-square (χ2) test. Results: Of 1800 invited participants, 977 completed the survey (54%). In the moderate and high-risk scenarios, 89.2 and 90.6% respectively, would like to receive information about a potential hereditary risk of CRC (χ2, p =.755). The desire to be informed was higher among women (91.5%) than men (87.0%, χ2, p =.044). No significant differences were found when comparing different age groups, educational levels, place of residence and having children or not. The preferred source of risk information was a healthcare professional in both moderate and high-risk scenarios (80.1 and 75.5%). However, 18.1 and 20.1% respectively would prefer to be informed by a family member. Assuming that healthcare professionals disclosed the information, the favoured mode of information was letter and phone (38.4 and 33.2%). Conclusions: In this study a majority of respondents wanted to be informed about a potential hereditary risk of CRC and preferred healthcare professionals to communicate this information. The two presented levels of CRC lifetime risk did not significantly affect the interest in being informed. Our data offer insights into the needs and preferences of the Swedish population, providing a rationale for developing complementary healthcare-assisted communication pathways to realise the full potential of targeted prevention of hereditary CRC. [ABSTRACT FROM AUTHOR]

Background: To evaluate the psychosocial consequences of surveillance with whole-body MRI (WB-MRI) in individuals with the heritable TP53-related cancer (hTP53rc) syndrome, also known as the Li-Fraumeni syndrome, with regard to cancer worry, perceived benefits and risks to surveillance and overall health., Patients and Methods: Since 2016, the national Swedish TP53 Study (SWEP53) has offered surveillance with WB-MRI to all individuals with hTP53rc syndrome. Seventy-five individuals have been included in the study. Sixty consecutive participants fulfilled a base-line evaluation as well as an evaluation after 1 year with structured questionnaires including the Cancer Worry Scale (CWS), perceived benefits and risks of surveillance, and the 36-item Short Form Survey (SF-36). Individuals with or without previous personal cancer diagnosis were enrolled and results at baseline and after 1 year of surveillance were compared. For SF-36, a comparison with the normal population was also made., Results: Participants with previous cancer tend to worry more about cancer, but both individuals with and without cancer had a positive attitude toward surveillance with no differences regarding perceived benefits and barriers to surveillance. Participants with a previous cancer scored significantly lower on some of the SF-36 subscales, but between-group differences were found only for social functioning after 1 year., Conclusions: Surveillance with WB-MRI is feasible from a psychosocial point of view both among TP53 carriers with as well as without a previous history of cancer and does not increase cancer worry in any of the groups., Plain Language Summary: Individuals with heritable TP53-related cancer syndrome (also known as the Li-Fraumeni syndrome) have a high lifetime risk of developing cancer. These TP53 carriers are offered surveillance with whole-body MRI to detect cancer early. There are few reports of the psychosocial impact of surveillance. In this study, we wanted to evaluate cancer worry, benefits and barriers to participation, and perceived overall health. Our study shows no increase in cancer worry after 1 year of surveillance, regardless of previous cancer., (© 2023 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)