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3 pages, 176 KiB

Open AccessEditorial

Precision Healthcare and Interventions in Hereditary Breast and Ovarian Cancer and Lynch Syndrome

by Maria C. Katapodi

Cancers 2023, 15(23), 5601; https://doi.org/10.3390/cancers15235601 - 27 Nov 2023

Viewed by 1196

Abstract

Precision health refers to personalized healthcare that combines genetic and genomic sequence, protein, metabolite, and microbiome information (collectively known as “omics” information) with lifestyle, social, economic, cultural, and environmental influences to help individuals achieve optimal health and well-being [...] Full article

(This article belongs to the Special Issue Precision Health Care and Interventions in Hereditary Breast and Ovarian Cancer and Lynch Syndrome)

Research

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13 pages, 834 KiB

Open AccessArticle

Intention to Inform Relatives, Rates of Cascade Testing, and Preference for Patient-Mediated Communication in Families Concerned with Hereditary Breast and Ovarian Cancer and Lynch Syndrome: The Swiss CASCADE Cohort

by Mahesh Sarki, Chang Ming, Souria Aissaoui, Nicole Bürki, Maria Caiata-Zufferey, Tobias Ephraim Erlanger, Rossella Graffeo-Galbiati, Karl Heinimann, Viola Heinzelmann-Schwarz, Christian Monnerat, Nicole Probst-Hensch, Manuela Rabaglio, Ursina Zürrer-Härdi, Pierre Olivier Chappuis, Maria C. Katapodi and on behalf of the CASCADE Consortium

Cancers 2022, 14(7), 1636; https://doi.org/10.3390/cancers14071636 - 23 Mar 2022

Cited by 11 | Viewed by 4056

Abstract

Cascade screening for Tier 1 cancer genetic conditions is a significant public health intervention because it identifies untested relatives of individuals known to carry pathogenic variants associated with hereditary breast and ovarian cancer (HBOC) and Lynch syndrome (LS). The Swiss CASCADE is a [...] Read more.

Cascade screening for Tier 1 cancer genetic conditions is a significant public health intervention because it identifies untested relatives of individuals known to carry pathogenic variants associated with hereditary breast and ovarian cancer (HBOC) and Lynch syndrome (LS). The Swiss CASCADE is a family-based, open-ended cohort, including carriers of HBOC- and LS-associated pathogenic variants and their relatives. This paper describes rates of cascade screening in relatives from HBOC- and LS- harboring families, examines carriers’ preferences for communication of testing results, and describes theory-based predictors of intention to invite relatives to a cascade screening program. Information has been provided by 304 index cases and 115 relatives recruited from September 2017 to December 2021. On average, 10 relatives per index case were potentially eligible for cascade screening. Approximately 65% of respondents wanted to invite relatives to the cohort, and approximately 50% indicated a preference for patient-mediated communication of testing results, possibly with the assistance of digital technology. Intention to invite relatives was higher for first- compared to second- and third-degree relatives, but was not different between syndromes or based on relatives’ gender. The family environment and carrying pathogenic variants predicts intention to invite relatives. Information helps optimize delivery of tailored genetic services. Full article

(This article belongs to the Special Issue Precision Health Care and Interventions in Hereditary Breast and Ovarian Cancer and Lynch Syndrome)

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18 pages, 864 KiB

Open AccessArticle

Impact of BRCA Status on Reproductive Decision-Making and Self-Concept: A Mixed-Methods Study Informing the Development of Tailored Interventions

by Sharlene Hesse-Biber, Memnun Seven, Jing Jiang, Sara Van Schaik and Andrew A. Dwyer

Cancers 2022, 14(6), 1494; https://doi.org/10.3390/cancers14061494 - 15 Mar 2022

Cited by 6 | Viewed by 2740

Abstract

This mixed-methods study sought to deepen our understanding of self-concept and experiences in balancing cancer risk/reproductive decisions after learning of BRCA+ status. First, a quantitative survey of BRCA+ women (n = 505) examined the childbearing status, risk-reducing surgery, and self-concept. [...] Read more.

This mixed-methods study sought to deepen our understanding of self-concept and experiences in balancing cancer risk/reproductive decisions after learning of BRCA+ status. First, a quantitative survey of BRCA+ women (n = 505) examined the childbearing status, risk-reducing surgery, and self-concept. At the time of testing, 307/505 (60.8%) women were of reproductive age (<40 years-old), 340/505 (67.3%) had children, and 317/505 (62.8%) had undergone risk-reducing surgery. A younger age at the time of the testing was significantly associated with the decision to have children after learning BRCA+ status or undergoing risk-reducing surgery (p < 0.001). Compared to older women, BRCA+ women of reproductive age, exhibited a more negative self-concept with significantly higher vulnerability ratings (p < 0.01). Women with a cancer diagnosis exhibited a more negative mastery ratings and worse vulnerability ratings (p < 0.01) than women without a cancer history. Compared to childless counterparts, significantly higher vulnerability ratings were observed among BRCA+ women who had children before learning their BRCA status and/or undergoing risk-reducing surgery (p < 0.001). Subsequently, a subset of women (n = 40) provided in-depth interviews to explore their experiences in decision-making. The interviews provided insights into the effects of BRCA status on decisions regarding relationships, childbearing, cancer risk management, and communicating BRCA risk to children. Integrating quantitative and qualitative findings identifies targets for tailored interventions to enhance precision health for BRCA+ women of reproductive age. Full article

(This article belongs to the Special Issue Precision Health Care and Interventions in Hereditary Breast and Ovarian Cancer and Lynch Syndrome)

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11 pages, 274 KiB

Open AccessArticle

Genetic Literacy and Communication of Genetic Information in Families Concerned with Hereditary Breast and Ovarian Cancer: A Cross-Study Comparison in Two Countries and within a Timeframe of More Than 10 Years

by Carla Pedrazzani, Chang Ming, Nicole Bürki, Maria Caiata-Zufferey, Pierre O. Chappuis, Debra Duquette, Karl Heinimann, Viola Heinzelmann-Schwarz, Rossella Graffeo-Galbiati, Sofia D. Merajver, Kara J. Milliron, Christian Monnerat, Olivia Pagani, Manuela Rabaglio and Maria C. Katapodi

Cancers 2021, 13(24), 6254; https://doi.org/10.3390/cancers13246254 - 13 Dec 2021

Cited by 7 | Viewed by 3002

Abstract

Examining genetic literacy in families concerned with hereditary breast and ovarian cancer (HBOC) helps understand how genetic information is passed on from individuals who had genetic counseling to their at-risk relatives. This cross-study comparison explored genetic literacy both at the individual and the [...] Read more.

Examining genetic literacy in families concerned with hereditary breast and ovarian cancer (HBOC) helps understand how genetic information is passed on from individuals who had genetic counseling to their at-risk relatives. This cross-study comparison explored genetic literacy both at the individual and the family level using data collected from three sequential studies conducted in the U.S. and Switzerland over ≥10 years. Participants were primarily females, at-risk or confirmed carriers of HBOC-associated pathogenic variants, who had genetic counselling, and ≥1 of their relatives who did not. Fifteen items assessed genetic literacy. Among 1933 individuals from 518 families, 38.5% had genetic counselling and 61.5% did not. Although genetic literacy was higher among participants who had counselling, some risk factors were poorly understood. At the individual level, genetic literacy was associated with having counselling, ≤5 years ago, higher education, and family history of cancer. At the family level, genetic literacy was associated with having counselling, higher education, and a cancer diagnosis. The findings suggest that specific genetic information should be emphasized during consultations, and that at-risk relatives feel less informed about inherited cancer risk, even if information is shared within families. There is a need to increase access to genetic information among at-risk individuals. Full article

(This article belongs to the Special Issue Precision Health Care and Interventions in Hereditary Breast and Ovarian Cancer and Lynch Syndrome)

Review

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15 pages, 2969 KiB

Open AccessReview

Regulatory T Cells in Ovarian Carcinogenesis and Future Therapeutic Opportunities

by Emily Cassar, Apriliana E. R. Kartikasari and Magdalena Plebanski

Cancers 2022, 14(22), 5488; https://doi.org/10.3390/cancers14225488 - 8 Nov 2022

Cited by 5 | Viewed by 1958

Abstract

Regulatory T cells (Tregs) have been shown to play a role in the development of solid tumors. A better understanding of the biology of Tregs, immune suppression by Tregs, and how cancer developed with the activity of Tregs has facilitated the development of [...] Read more.

Regulatory T cells (Tregs) have been shown to play a role in the development of solid tumors. A better understanding of the biology of Tregs, immune suppression by Tregs, and how cancer developed with the activity of Tregs has facilitated the development of strategies used to improve immune-based therapy. In ovarian cancer, Tregs have been shown to promote cancer development and resistance at different cancer stages. Understanding the various Treg-mediated immune escape mechanisms provides opportunities to establish specific, efficient, long-lasting anti-tumor immunity. Here, we review the evidence of Treg involvement in various stages of ovarian cancer. We further provide an overview of the current and prospective therapeutic approaches that arise from the modulation of Treg-related tumor immunity at those specific stages. Finally, we propose combination strategies of Treg-related therapies with other anti-tumor therapies to improve clinical efficacy and overcome tumor resistance in ovarian cancer. Full article

(This article belongs to the Special Issue Precision Health Care and Interventions in Hereditary Breast and Ovarian Cancer and Lynch Syndrome)

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11 pages, 603 KiB

Open AccessReview

Mutation Patterns in Portuguese Families with Hereditary Breast and Ovarian Cancer Syndrome

by Rodrigo Vicente, Diogo Alpuim Costa, Marina Vitorino, Ana Duarte Mendes, Catarina Santos and Mário Fontes-Sousa

Cancers 2022, 14(19), 4717; https://doi.org/10.3390/cancers14194717 - 28 Sep 2022

Cited by 3 | Viewed by 2825

Abstract

Germline pathogenic variants in the Breast Cancer Genes 1 (BRCA1) and 2 (BRCA2) are responsible for Hereditary Breast and Ovarian Cancer (HBOC) syndrome. Genetic susceptibility to breast cancer accounts for 5–10% of all cases, phenotypically presenting with characteristics such [...] Read more.

Germline pathogenic variants in the Breast Cancer Genes 1 (BRCA1) and 2 (BRCA2) are responsible for Hereditary Breast and Ovarian Cancer (HBOC) syndrome. Genetic susceptibility to breast cancer accounts for 5–10% of all cases, phenotypically presenting with characteristics such as an autosomal dominant inheritance pattern, earlier age of onset, bilateral tumours, male breast cancer, and ovarian tumours, among others. BRCA2 pathogenic variant is usually associated with other cancers such as melanoma, prostate, and pancreatic cancers. Many rearrangements of different mutations were found in both genes, with some ethnic groups having higher frequencies of specific mutations due to founder effects. Despite the heterogeneity of germline BRCA1/BRCA2 mutations in Portuguese breast or/and ovarian cancer families, the first described founder mutation in the BRCA2 gene (c.156_157insAlu) and two other variants in the BRCA1 gene (c.3331_3334del and c.2037delinsCC) contribute to about 50% of all pathogenic mutations. Furthermore, the families with the BRCA1 c.3331_3334del or the c.2037delinsCC mutations share a common haplotype, suggesting that these may also be founder mutations in the Portuguese population. Identifying specific and recurrent/founder mutations plays an important role in increasing the efficiency of genetic testing since it allows the use of more specific, cheaper and faster strategies to screen HBOC families. Therefore, this review aims to describe the mutational rearrangements of founder mutations and evaluate their impact on the genetic testing criteria for HBOC families of Portuguese ancestry. Full article

(This article belongs to the Special Issue Precision Health Care and Interventions in Hereditary Breast and Ovarian Cancer and Lynch Syndrome)

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20 pages, 390 KiB

Open AccessReview

Controversies and Open Questions in Management of Cancer-Free Carriers of Germline Pathogenic Variants in BRCA1/BRCA2

by Rinat Bernstein-Molho, Eitan Friedman and Ella Evron

Cancers 2022, 14(19), 4592; https://doi.org/10.3390/cancers14194592 - 22 Sep 2022

Cited by 4 | Viewed by 2210

Abstract

Females harboring germline BRCA1/BRCA2 (BRCA) P/LPV are offered a tight surveillance scheme from the age of 25–30 years, aimed at early detection of specific cancer types, in addition to risk-reducing strategies. Multiple national and international surveillance guidelines have been published and [...] Read more.

Females harboring germline BRCA1/BRCA2 (BRCA) P/LPV are offered a tight surveillance scheme from the age of 25–30 years, aimed at early detection of specific cancer types, in addition to risk-reducing strategies. Multiple national and international surveillance guidelines have been published and updated over the last two decades from geographically diverse countries. We searched for guidelines published between 1 January 2015 and 1 May 2022. Differences between guidelines on issues such as primary prevention, mammography screening in young (<30 years) carriers, MRI screening in carriers above age 65 years, breast imaging (if any) after risk-reducing bilateral mastectomy, during pregnancy, and breastfeeding, and hormone-replacement therapy, are just a few notable examples. Beyond formal guidelines, BRCA carriers’ concerns also focus on the timing of risk-reducing surgeries, fertility preservation, management of menopausal symptoms in cancer survivors, and pancreatic cancer surveillance, issues that, for some, there are no data to support evidence-based recommendations. This review discusses these unsettled issues, emphasizing the importance of future studies to enable global guideline harmonization for optimal surveillance strategies. Moreover, it raises the unmet need for personalized risk stratification and surveillance in BRCA P/LPV carriers. Full article

(This article belongs to the Special Issue Precision Health Care and Interventions in Hereditary Breast and Ovarian Cancer and Lynch Syndrome)

21 pages, 3308 KiB

Open AccessReview

Lynch Syndrome: From Carcinogenesis to Prevention Interventions

by Donatella Gambini, Stefano Ferrero and Elisabetta Kuhn

Cancers 2022, 14(17), 4102; https://doi.org/10.3390/cancers14174102 - 24 Aug 2022

Cited by 10 | Viewed by 5167

Abstract

Lynch syndrome (LS) is the most common inherited disorder responsible for an increased risk of developing cancers at different sites, most frequently in the gastrointestinal and genitourinary tracts, caused by a germline pathogenic variant affecting the DNA mismatch repair system. Surveillance and risk-reducing [...] Read more.

Lynch syndrome (LS) is the most common inherited disorder responsible for an increased risk of developing cancers at different sites, most frequently in the gastrointestinal and genitourinary tracts, caused by a germline pathogenic variant affecting the DNA mismatch repair system. Surveillance and risk-reducing procedures are currently available and warranted for LS patients, depending on underlying germline mutation, and are focused on relevant targets for early cancer diagnosis or primary prevention. Although pharmacological approaches for preventing LS-associated cancer development were started many years ago, to date, aspirin remains the most studied drug intervention and the only one suggested by the main surveillance guidelines, despite the conflicting findings. Furthermore, we also note that remarkable advances in anticancer drug discovery have given a significant boost to the application of novel immunological strategies such as immunocheckpoint inhibitors and vaccines, not only for cancer treatment, but also in a preventive setting. In this review, we outline the clinical, biologic, genetic, and morphological features of LS as well as the recent three-pathways carcinogenesis model. Furthermore, we provide an update on the dedicated screening, surveillance, and risk-reducing strategies for LS patients and describe emerging opportunities of harnessing the immune system. Full article

(This article belongs to the Special Issue Precision Health Care and Interventions in Hereditary Breast and Ovarian Cancer and Lynch Syndrome)

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