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Dervin T, Ranisavjevic N, Laot L, Mayeur A, Duperier C, Steffann J, Borghese R, Stoppa-Lyonnet D, Frydman N, Benachi A, Sonigo C, Grynberg M. Knowledge, acceptability and personal attitude toward pre-implantation 1 genetic testing (PGT) and pre-natal diagnosis (PND) for females carrying BRCA pathogenic variant according to fertility preservation experience. J Assist Reprod Genet 2023; 40:1381-1390. [PMID: 37154838 PMCID: PMC10310597 DOI: 10.1007/s10815-023-02798-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Accepted: 04/04/2023] [Indexed: 05/10/2023] Open
Abstract
PURPOSE Preimplantation genetic testing (PGT-M) and prenatal diagnosis (PND) followed by medical termination of pregnancy when the fetus is affected are two procedures developed to avoid the transmission of a severe hereditary disease which can be proposed to females that carried BRCA pathogenic variants. These females can also be offered fertility preservation (FP) when diagnosed with cancer or even before a malignancy occurs. The aim of the study was to evaluate the acceptability and personal attitude of women carrying a BRCA mutation toward techniques that can prevent BRCA transmission to their progeny. METHODS Female mutated for BRCA1 or BRCA2 were invited to complete an online survey of 49 queries anonymously between June and August 2022. RESULTS A total of 87 participants responded to the online survey. Overall, 86.2% of women considered that PGT-M should be proposed to all BRCA mutation carriers regardless of the severity of the family history, and 47.1% considered or would consider PGT-M for themselves. For PND, these percentages were lower reaching 66.7% and 29.9%, respectively. Females with personal history of breast cancer or FP achievement were more prone to undergo PND for themselves despite the overall acceptability of this procedure. Among the subgroup who had undergone FP (n = 58), there was no significant difference in acceptance of principle and personal attitude toward PGT-M and PND compared to the group without FP. CONCLUSION BRCA pathogenic variants female carriers do need information about reproductive issues, even if they are not prone to undergo PGT-M nor PND for themselves. TRIAL REGISTRATION NUMBER N/A.
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Affiliation(s)
- Traicie Dervin
- Department of Reproductive Medicine and Fertility Preservation, Université Paris-Saclay, Assistance Publique, Hôpitaux de Paris, Antoine Beclere Hospital, F-92140, Clamart, France
| | - Noémie Ranisavjevic
- Department of Reproductive Medicine, CHU and University of Montpellier, 371 Avenue du Doyen Gaston, Giraud, 34090, Montpellier, France
| | - Lucie Laot
- Department of Reproductive Medicine and Fertility Preservation, Université Paris-Saclay, Assistance Publique, Hôpitaux de Paris, Antoine Beclere Hospital, F-92140, Clamart, France
| | - Anne Mayeur
- Service de Biologie de La Reproduction - CECOS, Université Paris-Saclay, Assistance Publique Hôpitaux de Paris, Antoine Beclere Hospital, F-92140, Clamart, France
| | - Constance Duperier
- Department of Reproductive Medicine and Fertility Preservation, Université Paris-Saclay, Assistance Publique, Hôpitaux de Paris, Antoine Beclere Hospital, F-92140, Clamart, France
| | - Julie Steffann
- Université Paris Cité, Imagine INSERM UMR1163, Service de Médecine Génomique Des Maladies Rares, Groupe Hospitalier Necker-Enfants Malades, AP-HP, Paris, France
| | - Roxana Borghese
- Université Paris Cité, Imagine INSERM UMR1163, Service de Médecine Génomique Des Maladies Rares, Groupe Hospitalier Necker-Enfants Malades, AP-HP, Paris, France
| | | | - Nelly Frydman
- Service de Biologie de La Reproduction - CECOS, Université Paris-Saclay, Assistance Publique Hôpitaux de Paris, Antoine Beclere Hospital, F-92140, Clamart, France
| | - Alexandra Benachi
- Department of Obstetrics and Gynecology, DMU Santé Des Femmes Et Des Nouveau-Nés, Université Paris-Saclay, Assistance Publique Hôpitaux de Paris, Antoine Beclere Hospital, F-92140, Clamart, France
| | - Charlotte Sonigo
- Department of Reproductive Medicine and Fertility Preservation, Université Paris-Saclay, Assistance Publique, Hôpitaux de Paris, Antoine Beclere Hospital, F-92140, Clamart, France
- Université Paris Saclay, Inserm, Physiologie Et Physiopathologie Endocrinienne, F-94276, Le Kremlin-Bicêtre, France
| | - Michael Grynberg
- Department of Reproductive Medicine and Fertility Preservation, Université Paris-Saclay, Assistance Publique, Hôpitaux de Paris, Antoine Beclere Hospital, F-92140, Clamart, France.
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Should Preimplantation Genetic Testing (PGT) Systematically Be Proposed to BRCA Pathogenic Variant Carriers? Cancers (Basel) 2022; 14:cancers14235769. [PMID: 36497251 PMCID: PMC9739906 DOI: 10.3390/cancers14235769] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Revised: 11/16/2022] [Accepted: 11/19/2022] [Indexed: 11/25/2022] Open
Abstract
Over the past years, BRCA genes pathogenic variants have been associated to reproductive issues. Indeed, evidence indicate that BRCA-mutated patients are not only at higher risk of developing malignancies, but may also present a reduction of the follicular stockpile. Given these characteristics, BRCA patients may be candidates to fertility preservation (FP) techniques or preimplantation genetic testing (PGT) to avoid the transmission of this inherited situation. Since the success rates of both procedures are highly related to the number of oocytes that could be recovered after ovarian stimulation, predicted by ovarian reserve tests, they are ideally performed before the diagnosis of cancer and its treatment. Despite the specific reproductive challenges related to BRCA status, no international guidelines for the application of PGT and FP in this subgroup of patients is currently available. The present article aims to review the available data regarding BRCA carriers' ovarian reserve and PGT success rates in oncologic and non-oncologic contexts, to determine the actual indication of PGT and further to improve patients' care pathway.
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Shah IH, Salo-Mullen EE, Amoroso KA, Kelsen D, Stadler ZK, Hamilton JG. Attitudes toward preimplantation genetic testing and quality of life among individuals with hereditary diffuse gastric cancer syndrome. Hered Cancer Clin Pract 2022; 20:31. [PMID: 36056367 PMCID: PMC9440538 DOI: 10.1186/s13053-022-00239-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Accepted: 08/12/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Hereditary Diffuse Gastric Cancer (HDGC) syndrome is an autosomal dominant hereditary cancer predisposition associated with germline pathogenic/likely pathogenic variants in the CDH1 gene. Identifying early stage HDGC is difficult, and prophylactic measures can be effective in preventing incidence. Preimplantation Genetic Testing (PGT) can provide information about CDH1 variant status, HDGC risk, and limit familial transmission of CDH1 variants. To date, however, little is known about the attitudes of individuals with CDH1 variants towards PGT. METHODS Given that little is known about the reproductive attitudes of individuals with HDGC, we recruited participants with CDH1 variants from a familial gastric cancer registry and administered a cross-sectional survey with open- and closed-ended response items. We assessed attitudes regarding PGT and the effect of HDGC on quality of life. RESULTS Participants (n = 21) were predominantly partnered (61.9%), had a personal cancer history (71.4%), and had biological children (71.4%). Interest in learning about PGT was high; 66.7% of participants were interested in PGT and 90.5% approved of healthcare providers discussing PGT with individuals with CDH1 variants. Attitudes regarding personal use were varied. Among all participants, 35% would not, 25% were uncertain, and 40% would use PGT. Personal philosophy and preferences for family and reproduction were key factors related to PGT attitudes. HDGC had moderate effects on participants' quality of life, including social relationships, health behaviors, and emotional experiences including worry about cancer risk and guilt regarding familial implications. CONCLUSION PGT was identified by participants as acceptable for use in a variety of contexts and benefits of reproductive counseling involving PGT may extend beyond CDH1 carriers to family members' reproductive behaviors. Dispositions towards PGT are governed by personal philosophy or belief systems. These findings can help guide providers counseling individuals with CDH1 variants.
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Affiliation(s)
- Ibrahim H Shah
- Department of Psychiatry & Behavioral Sciences, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Erin E Salo-Mullen
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Kimberly A Amoroso
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - David Kelsen
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Department of Medicine, Weill Cornell Medical College, Cornell University, New York, NY, USA
| | - Zsofia K Stadler
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Department of Medicine, Weill Cornell Medical College, Cornell University, New York, NY, USA
| | - Jada G Hamilton
- Department of Psychiatry & Behavioral Sciences, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
- Department of Psychiatry, Weill Cornell Medical College, Cornell University, New York, NY, USA.
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Barnett M, Breen KE, Kennedy JA, Hernandez M, Matsoukas K, MacGregor M. Psychosocial interventions and needs among individuals and families with Li-Fraumeni syndrome: A scoping review. Clin Genet 2022; 101:161-182. [PMID: 34355387 DOI: 10.1111/cge.14042] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 07/28/2021] [Accepted: 07/29/2021] [Indexed: 01/20/2023]
Abstract
Li-Fraumeni syndrome (LFS), a rare cancer predisposition syndrome caused by germline mutations in the TP53 gene, is associated with significant lifetime risk of developing cancer and warrants extensive and long-term surveillance. There are psychosocial impacts on individuals and families living with this condition, from the initial diagnosis throughout multiple stages across the lifespan, but these impacts have not been systematically reviewed and organized. The objective of this scoping review was to synthesize and characterize the literature on psychosocial screening and outcomes, educational needs, support services, and available interventions for patients and families with LFS. A systematic search of six databases was most recently conducted in August 2020: (PubMed/MEDLINE (NLM), EMBASE (Elsevier), Cochrane Library (Wiley), CINAHL (EBSCO), PsycINFO (OVID), and Web of Science (Clarivate Analytics). A total of 15 757 titles were screened, and 24 articles included. Several important themes were identified across studies: factors associated with TP53 genetic testing, LFS surveillance, psychological outcomes, and communication. Findings related to these themes were organized into age-specific categories (age agnostic/across the lifespan, childhood, adolescence and young adulthood, and adulthood).
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Affiliation(s)
- Marie Barnett
- Department of Psychiatry, Memorial Sloan Kettering Cancer Center, New York City, USA
| | - Kelsey E Breen
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York City, USA
| | - Jennifer A Kennedy
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York City, USA
| | - Marisol Hernandez
- Medical Library, Memorial Sloan Kettering Cancer Center, New York City, USA
- Medical Library, City University of New York School of Medicine, New York City, USA
| | | | - Meredith MacGregor
- Department of Child and Adolescent Psychiatry and Behavioral Sciences, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
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Reproductive and Hormonal Considerations in Women at Increased Risk for Hereditary Gynecologic Cancers: Society of Gynecologic Oncology and American Society for Reproductive Medicine Evidence-Based Review. Gynecol Oncol 2019; 155:508-514. [DOI: 10.1016/j.ygyno.2019.06.017] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2019] [Revised: 06/14/2019] [Accepted: 06/18/2019] [Indexed: 12/20/2022]
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Scott D, Friedman S, Telli ML, Kurian AW. Decision Making About Genetic Testing Among Women With a Personal and Family History of Breast Cancer. JCO Oncol Pract 2019; 16:e37-e55. [PMID: 31613719 DOI: 10.1200/jop.19.00221] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
PURPOSE To understand genetic testing use and decision making among patients with high genetic risk. MATERIALS AND METHODS A survey of breast cancer survivors was administered online by a hereditary cancer nonprofit organization, Facing Our Risk of Cancer Empowered, from October 2017 to March 2018. RESULTS Of 1,322 respondents, 46% had breast cancer at age < 45 years, 61% had a first-degree relative with cancer, and 84% underwent genetic testing, of whom 56% had a risk-associated pathogenic variant. Most (86%; 95% CI, 84% to 88%) tested respondents were very satisfied with their testing decision, versus 34% (95% CI, 27% to 41%) of untested respondents. Factors that encouraged testing included relatives' cancer risk (75%; 95% CI, 73% to 78%), clinicians' recommendations (68%; 95% CI, 66% to 71%), and potential treatment implications (67%; 95% CI, 64% to 69%). Factors that discouraged testing included insurance concerns (14%; 95% CI, 12% to 16%), cost (14%; 95% CI, 12% to 16%), and discrimination (9%; 95% CI, 7% to 11%). Thirty-nine percent (95% CI, 36% to 41%) recalled hearing from a clinician that genetic discrimination is illegal. Respondents often recalled clinicians informing them about inheritance patterns (65%; 95% CI, 62% to 67%), surgical implications (65%; 95% CI, 63% to 68%), and other cancer risks (66%; 95% CI, 63% to 68%) but less often that results could have potential implications for clinical trial eligibility (38%; 95% CI, 36% to 42%) or targeted therapies (14%; 95% CI, 12% to 16%). Patients who had genetic counseling were twice as likely to recall clinicians informing them about all queried topics. Results did not vary by diagnosis year. CONCLUSION Among patients with high genetic risk, clinicians' recommendations, potential treatment implications, and protections against discrimination were motivating factors to undergo genetic testing, but fewer than half recalled clinicians providing all this information, and this did not improve over time. Clinicians influence testing decisions and should inform patients about legal protections and treatment implications.
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Affiliation(s)
- Danika Scott
- Stanford University School of Medicine, Stanford, CA
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Chen LM, Blank SV, Burton E, Glass K, Penick E, Woodard T. Reproductive and hormonal considerations in women at increased risk for hereditary gynecologic cancers: Society of Gynecologic Oncology and American Society for Reproductive Medicine Evidence-Based Review. Fertil Steril 2019; 112:1034-1042. [PMID: 31606136 DOI: 10.1016/j.fertnstert.2019.07.1349] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2019] [Revised: 06/14/2019] [Accepted: 06/18/2019] [Indexed: 12/21/2022]
Abstract
Providers who care for women at risk for hereditary gynecologic cancers must consider the impact of these conditions on reproductive and hormonal health. This document reviews potential options for cancer prevention, family building, genetic testing and management of surgical menopause in this patient population.
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Affiliation(s)
- Lee-May Chen
- University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California.
| | - Stephanie V Blank
- Icahn and Blavatnik Family Women's Health Research Institute, New York, New York
| | | | - Karen Glass
- CReATe Fertility Centre, Toronto, Ontario, Canada
| | - Emily Penick
- Walter Reed National Military Medical Center, Bethesda, Maryland
| | - Terri Woodard
- University of Texas MD Anderson Cancer Center, Houston, Texas; Baylor College of Medicine, Houston, Texas
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8
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Oribamise EI, Ashiru OA, Iloabachie EC, Osumah JG, Moruf OO. Preimplantation Genetic Testing for Breast Cancer. Niger Med J 2019; 60:99-105. [PMID: 31543559 PMCID: PMC6737793 DOI: 10.4103/nmj.nmj_124_18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Breast cancer (BC), a malignant tumor characterized mainly by a lump in the breast and a change in breast shape, has plagued many women of childbearing age in Nigeria today. This has thus propelled many to find both prophylactic and curative agents to combat BC in affected persons. This article extensively reviews a method of preventing BC in the offspring of affected parents, known as preimplantation genetic testing (PGT) – an assisted reproductive technique that selects genetically unaffected embryo(s) to be transferred to the uterus of a mother upon in vitro fertilization and standard genetic analysis. The present study also seeks to present the techniques involved in PGT that have been reported to prevent the inheritance of BC, its benefits and risks, related case studies in Africa and other continents, and ethical issues surrounding the application of assisted reproduction for BC testing. To achieve these, a thorough search was conducted in reputable scientific journals of reproduction and cancer, and expert knowledge was consulted with regard to these aspects of health and reproduction. Upon reviewing this very important subject, it was confirmed that the beneficial role of assisted reproduction in the field of science and the homes of many cannot be overestimated. This review of the role of PGT in BC prevention will enlighten the understanding of many – creating awareness that with PGT, BC-affected women can have not only children, but also healthy and genetically unaffected children.
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Affiliation(s)
- Eunice I Oribamise
- Medical ART Center, Institute of Reproductive Medicine, Ikeja, Lagos State, Nigeria.,Department of Anatomy, Babcock University, Ilishan-Remo, Ogun State, Nigeria
| | - Oladapo A Ashiru
- Medical ART Center, Institute of Reproductive Medicine, Ikeja, Lagos State, Nigeria
| | - Ebele C Iloabachie
- Medical ART Center, Institute of Reproductive Medicine, Ikeja, Lagos State, Nigeria
| | - Jumoke G Osumah
- Medical ART Center, Institute of Reproductive Medicine, Ikeja, Lagos State, Nigeria
| | - Oladimeji O Moruf
- Medical ART Center, Institute of Reproductive Medicine, Ikeja, Lagos State, Nigeria
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Mor P, Brennenstuhl S, Metcalfe KA. Uptake of Preimplantation Genetic Diagnosis in Female BRCA1 and BRCA2 Mutation Carriers. J Genet Couns 2018; 27:1386-1394. [DOI: 10.1007/s10897-018-0264-2] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2017] [Accepted: 05/22/2018] [Indexed: 01/26/2023]
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The Relationship Between Body Image, Gender, Subjective Norms, and the Decision to Undergo Preventive Mastectomy Among Arab and Jewish BRCA Carriers. Cancer Nurs 2017; 41:255-262. [PMID: 28481778 DOI: 10.1097/ncc.0000000000000503] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND Carriers for a mutation in BRCA1/2 genes have a high, lifelong risk for developing breast cancer. Preventive mastectomy is considered an effective risk reduction surgery. Many factors might affect the decision to undergo preventive mastectomy, including culture, perceived body image after mastectomy and important others opinion. OBJECTIVE The aim of this study is to evaluate BRCA mutation carriers' decision to undergo preventive mastectomy and the relationship between culture, gender, body image, and the decision. METHODS The study was a cross-sectional design where Arab and Jewish men and women were requested to imagine that they were/their spouse was a BRCA mutation carrier. The sample consisted of 200 participants, 101 Arab and 99 Jews, included 101 women and 99 men. RESULTS The results show a high intention to undergo preventive mastectomy. Being Arab and having a more positive perception of body image after the surgery were connected to more intention to undergo the surgery. Also, those who intended to choose the surgery considered more the opinions of important others. CONCLUSIONS The results point to the importance of partners' involvement in the decision to undergo preventive mastectomy. Also, important others (relatives, friends, and health caregivers) have an impact on the decision. IMPLICATIONS FOR PRACTICE Nurses need to consider cultural aspects of patients considering a decision about whether to undergo preventive mastectomy. Understanding the important others who might influence the decision and including them in the decision process are both essential.
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Dagan E, Birenbaum-Carmeli D, Friedman E, Feldman B. Performing and Declining PGD: Accounts of Jewish Israeli Women Who Carry a BRCA1/2 Mutation or Partners of Male Mutation Carriers. J Genet Couns 2017; 26:1070-1079. [PMID: 28265801 DOI: 10.1007/s10897-017-0087-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2015] [Accepted: 02/21/2017] [Indexed: 01/30/2023]
Abstract
To describe factors associated with preimplantation genetic diagnosis (PGD) decisions among Jewish Israeli BRCA1/2 carriers or spouses of a male carrier, we contacted all women who initiated PGD consultation for embryonic BRCA1/2 mutation detection at Sheba Medical Center, prior to March 2014. Applying a qualitative approach, we asked women to elaborate on the factors they considered in either opting for PGD or discontinuing the screening procedure. Participants were 18 Jewish Israeli women; 14 were carriers of one of the Ashkenazi founder mutations in BRCA1/2, and four were spouses of male mutation carriers, who underwent at least one cycle of PGD. Prior to seeking PGD, ten of the women had no children. At the time of the interview, all but three had at least one child. Three factors emerged as key motivators for PGD: having witnessed the disease in a close relative (n = 12); prior IVF treatment for infertility (n = 12); and having pre-existing frozen embryos (n = 6). Ten women withdrew from the PGD process due to clinical, logistical, and financial reasons. In conclusion, most women decided to withdraw from PGD instead of continuing until a successful conception was achieved. Those who opted for PGD attributed their discontinuation of further screening to the emotional burden that is greatly intensified by practical difficulties.
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Affiliation(s)
- Efrat Dagan
- Department of Nursing, University of Haifa, PO Box 3498838, Haifa, Israel.
| | | | - Eitan Friedman
- The Susanne-Levy Gertner Oncogenetics Unit, Sheba Medical Center, PO Box 52621, Tel Aviv, Israel.,Sackler School of Medicine, Tel Aviv University, PO Box 39040, Tel-Aviv, Israel
| | - Baruch Feldman
- Sheba Medical Center, The Danek Gertner Institute of Human Genetics, PO Box 52621, Tel Aviv, Israel
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Gietel-Habets JJG, de Die-Smulders CEM, Derks-Smeets IAP, Tibben A, Tjan-Heijnen VCG, van Golde R, Gomez-Garcia E, Kets CM, van Osch LADM. Awareness and attitude regarding reproductive options of persons carrying a BRCA mutation and their partners. Hum Reprod 2017; 32:588-597. [PMID: 28073972 DOI: 10.1093/humrep/dew352] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2016] [Accepted: 12/23/2016] [Indexed: 11/14/2022] Open
Abstract
STUDY QUESTION To what extent are BRCA mutation carriers and their partners in the Netherlands aware about preimplantation genetic diagnosis (PGD) and prenatal diagnosis (PND) as reproductive options and what is their attitude towards these options? SUMMARY ANSWER Awareness of PGD (66%) and PND (61%) among BRCA mutation carriers and their partners is relatively high and 80% and 26%, respectively, of BRCA carriers and their partners find offering PGD and PND for hereditary breast and ovarian cancer (HBOC) acceptable. WHAT IS KNOWN ALREADY Internationally, awareness of PGD among persons with a genetic cancer predisposition appears to be relatively low (35%) and although acceptability is generally high (71%), only a small proportion of mutation carriers would consider using PGD (36%). However, for HBOC, there are no studies available that investigated the perspective of individuals with a confirmed BRCA1/2 mutation and their partners about PGD and PND including demographic and medical correlates of awareness and acceptability. STUDY DESIGN, SIZE, DURATION A cross-sectional survey was completed by 191 participants between July 2012 and June 2013. Participants were recruited through patient organizations (88%) and the databases of two Clinical Genetics departments in the Netherlands (12%). PARTICIPANTS/MATERIALS, SETTING, METHODS Male and female BRCA carriers and their partners completed an online survey, which assessed demographic and medical characteristics, and awareness, knowledge, acceptability and consideration of PGD and PND as main outcomes. Correlations between demographic and medical characteristics and the main outcomes were investigated. MAIN RESULTS AND ROLE OF CHANCE The majority of respondents were female (87%), of reproductive age (86%) and about half reported a desire for a child in the future. About two-thirds (66%) were aware of PGD and 61% of PND for HBOC. PGD knowledge was moderate (5.5 on a 9-point scale) and acceptability of PGD and PND for HBOC was 80% and 26%, respectively. A minority would personally consider using PGD (39%) or PND (20%). Individuals with a higher educational level were more likely to be aware of PGD (P < 0.001) and PND (P < 0.001) and persons with a more immediate child wish were more often aware of PGD (P = 0.044) and had more knowledge about PGD (P = 0.001). PGD acceptability was positively associated with knowledge about PGD (P = 0.047), and PND acceptability was higher among partners in comparison to carriers (P = 0.001). Participants with a history of cancer and with a higher perceived seriousness of breast and ovarian cancer were more likely to consider using PGD (P = 0.003 and P < 0.001 respectively) or PND (P = 0.021 and P = 0.017 respectively). LIMITATIONS, REASONS FOR CAUTION The response rate (23%) of participants invited by the clinical genetics departments was low, probably related to a simultaneous study that used a similar recruitment strategy within the same target group, which may have resulted in selection bias. Moreover, PGD knowledge was measured with an instrument that is not yet validated since to date such an instrument is not available in the literature. Finally, the cross-sectional design of this study limits us from drawing any causal conclusions. WIDER IMPLICATIONS OF THE FINDINGS Improvement of information provision remains needed, in order to timely inform all couples with HBOC about the available reproductive options and enable them to make a balanced reproductive decision. This may limit the risk of negative psychological impact due to decisional conflict and possible regret. STUDY FUNDING/COMPETING INTEREST(S) The Dutch breast cancer foundation Stichting Pink Ribbon (grant number 2010.PS11.C74). None of the authors have competing interests to declare. TRIAL REGISTRATION NUMBER Not applicable.
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Affiliation(s)
- J J G Gietel-Habets
- Department of Clinical Genetics, Maastricht University Medical Centre, PO Box 5800, 6202 AZ Maastricht, The Netherlands.,GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre+, PO Box 616, 6200 MD Maastricht, The Netherlands
| | - C E M de Die-Smulders
- Department of Clinical Genetics, Maastricht University Medical Centre, PO Box 5800, 6202 AZ Maastricht, The Netherlands.,GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre+, PO Box 616, 6200 MD Maastricht, The Netherlands
| | - I A P Derks-Smeets
- Department of Clinical Genetics, Maastricht University Medical Centre, PO Box 5800, 6202 AZ Maastricht, The Netherlands.,GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre+, PO Box 616, 6200 MD Maastricht, The Netherlands
| | - A Tibben
- Centre for Human and Clinical Genetics, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, The Netherlands
| | - V C G Tjan-Heijnen
- GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre+, PO Box 616, 6200 MD Maastricht, The Netherlands.,Department of Internal Medicine, division of Medical Oncology, Maastricht University Medical Centre+, PO Box 5800, 6202 AZ Maastricht, The Netherlands
| | - R van Golde
- Department of Obstetrics and Gynaecology, Maastricht University Medical Centre +, PO Box 5800, 6202 AZ Maastricht, The Netherlands
| | - E Gomez-Garcia
- Department of Clinical Genetics, Maastricht University Medical Centre, PO Box 5800, 6202 AZ Maastricht, The Netherlands.,GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre+, PO Box 616, 6200 MD Maastricht, The Netherlands
| | - C M Kets
- Department of Human Genetics, Radboud University Nijmegen Medical Centre, code 848, PO Box 9101, 6500 HB Nijmegen, The Netherlands
| | - L A D M van Osch
- Department of Clinical Genetics, Maastricht University Medical Centre, PO Box 5800, 6202 AZ Maastricht, The Netherlands.,Department of Health Promotion/CAPHRI, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands
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Dean M, Rauscher EA. “It was an Emotional Baby”: Previvors’ Family Planning Decision-Making Styles about Hereditary Breast and Ovarian Cancer Risk. J Genet Couns 2017; 26:1301-1313. [DOI: 10.1007/s10897-017-0069-8] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2016] [Accepted: 01/15/2017] [Indexed: 01/14/2023]
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Reproductive Decision-Making in Women with BRCA1/2 Mutations. J Genet Couns 2016; 26:594-603. [PMID: 27796678 DOI: 10.1007/s10897-016-0035-x] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2016] [Accepted: 10/07/2016] [Indexed: 12/19/2022]
Abstract
Expanded genetic testing of BRCA mutations has led to identification of more reproductive-aged women who test positive for the mutation which might impact attitudes and decisions about relationships, childbearing and the use of preimplantation genetic diagnosis (PGD) and prenatal diagnosis (PND). A cross-sectional survey was administered to 1081 self-reported BRCA carriers to investigate how knowledge of BRCA status influences these issues. The mean age at BRCA test disclosure was 44 years and 36 % reported a personal history of cancer. Of 163 women who were unpartnered, 21.5 % felt more pressure to get married. Of 284 women whose families were not complete, 41 % reported that carrier status impacted their decision to have biological children. Women with a history of cancer were more likely to report that knowledge of BRCA+ status impacted their decision to have a child (OR 1.8, 95 % CI 1-3.2). Fifty-nine percent thought PGD should be offered to mutation carriers and 55.5 % thought PND should be offered. In conclusion, knowledge of BRCA status impacts attitudes regarding relationships and childbearing, and most carriers believe that PGD and PND should be offered to other carriers. This study suggests that BRCA carriers desire and would benefit from reproductive counseling after test disclosure.
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Abstract
As health care providers, we play a crucial role in the assessment of a patient's risk for hereditary breast cancer syndromes. The panorama of genetic assessment and testing has evolved dramatically since the identification of the BRCA genes. Next-generation sequencing technology has facilitated the development of multigene panels, but 1 consequence has been an increased identification of pathogenic variants at odds with a family history as well as variants of uncertain significance for which treatment guidelines are not defined. Progress in this field requires close collaboration between patients and clinicians with a thorough understanding in cancer genetics.
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Mancini J, Mouret-Fourme E, Noguès C, Julian-Reynier C. Impact of BRCA1/2 mutation on young women's 5-year parenthood rates: a prospective comparative study (GENEPSO-PS cohort). Fam Cancer 2016; 14:273-9. [PMID: 25550141 DOI: 10.1007/s10689-014-9777-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Previous qualitative and intentions surveys have shown that the disclosure of a BRCA1/2 mutation might deter young women from becoming pregnant. However, to our knowledge, no comparative studies have ever documented the possibility that positive genetic test results might affect these women's future reproductive rates. Our aim was therefore to quantify the impact of BRCA1/2 mutation disclosure on long-term relationships between partners and childbearing rates. Participants were cancer-free women belonging to families in which a deleterious BRCA1/2 mutation had been identified, who had attended one of the 29 participating cancer genetic clinics for BRCA1/2 testing between 2000 and 2006. Logistic regression models were used to determine predictors of the 5-year self-reported parenthood rate. The sample consisted of 271 women aged 18-45 years (126 BRCA1/2 mutation carriers and 145 non-carriers). Couples had separated more frequently among BRCA1/2 carriers than non-carriers (10 vs. 3%, p = .040), especially among nulliparous carriers (13%). Among the 104 women who were childless at disclosure, disclosure of a BRCA1/2 mutation was not significantly associated with childbearing during the 5-year follow-up period [adjusted odds ratio .64, 95% confidence interval (CI) (.26, 1.57), p = .334]. Among the 167 women with at least one child at disclosure of a BRCA1/2 mutation had no conspicuous effect on the childbearing trends [adjOR .88, 95% CI (.35, 2.21), p = .787]. The disclosure of a BRCA1/2 mutation might impact couples' relationships and future mothering rates, particularly among nulliparous women. Studies on larger populations are now required to confirm these findings.
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Affiliation(s)
- Julien Mancini
- Aix Marseille Université, Inserm, IRD, UMR912 SESSTIM, 13385, Marseille, France,
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Quinn GP, Peshkin BN, Sehovic I, Bowman M, Tamargo C, Vadaparampil ST. Oncofertility in adolescent and young adult hereditary cancer: Considerations for genetics professionals. World J Med Genet 2015; 5:52-59. [DOI: 10.5496/wjmg.v5.i4.52] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2015] [Revised: 08/07/2015] [Accepted: 09/28/2015] [Indexed: 02/06/2023] Open
Abstract
Adolescents and young adults (AYA) with a cancer diagnosis or those at risk for cancer due to hereditary cancer syndromes may benefit from genetic counseling and testing not only to manage personal risk but also to address reproductive concerns, especially fertility. The opportunity for genetic counselors to provide important risk information is relevant to both the newly diagnosed as well as to unaffected carriers and survivors. However, genetic counselors may need additional training in reproductive options related to AYA cancer to provide this valuable counsel. This commentary uses hereditary breast and ovarian cancer syndrome as a model to highlight important considerations when discussing preimplanatation genetic diagnosis and prenatal diagnosis, particularly in the context of expanded testing for hereditary cancer risk including multigene panels or whole exome or whole genome sequencing. Other hereditary cancers are also addressed; however, less is known about the psychosocial and fertility concerns in these AYA populations. Additionally, we provide an overview of the concept of “oncofertility” - the linkage between cancer care and reproductive medicine that aims to expand the reproductive opportunities of cancer patients - and offer support for the expansion of guidelines to include genetic counselors in AYA cancer patients’ treatment planning related to reproductive health and fertility.
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Reproductive Decision-Making in MMR Mutation Carriers After Results Disclosure: Impact of Psychological Status in Childbearing Options. J Genet Couns 2015; 25:432-42. [PMID: 26392361 DOI: 10.1007/s10897-015-9888-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2015] [Accepted: 09/08/2015] [Indexed: 01/13/2023]
Abstract
Reproductive techniques such as prenatal diagnosis (PND) or preimplantation genetic diagnosis (PGD), although debated, are legally forbidden in France in case of Lynch syndrome. The preference of mutation carriers about their reproductive options is not systematically considered in France. We aimed to prospectively assess the reproductive preferences of mismatch repair mutation carriers consulting in our institution (2003-2010, n = 100). We also considered the short- and long-term post-disclosure psychological impact using the Impact of Events Scale-Revised questionnaire to measure the prevalence of posttraumatic stress disorder (PTSD) in those patients. Complete data were obtained for 34 respondents (17 males, 17 females, median age of 33.5 years [22-59]). Seventeen respondents (57 %) preferred spontaneous natural conception versus 28 % and 35 % choosing PND and PGD, respectively. At results disclosure, respondents mainly explained their distress by fear of premature death (43 %) and transmitting mutated genes (42 %). One year later, this last fear remained predominant in 55 % of subjects. None of the main socio-demographical, psychological or medical variables (including fear of transmitting mutations) was significantly associated with the reproductive preferences. Results disclosure had a real and time-decreasing psychological impact on mutation carriers. Reproductive techniques, expected to decrease the hereditary risk, were not significantly preferred to natural conception.
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Mauer C, Spencer S, Dungan J, Hurley K. Exploration of Male Attitudes on Partnerships and Sexuality with Female BRCA1/2 Mutation Carriers. J Genet Couns 2015; 25:290-7. [PMID: 26250348 DOI: 10.1007/s10897-015-9870-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2015] [Accepted: 07/23/2015] [Indexed: 11/24/2022]
Abstract
Women with BRCA mutations are inundated with decisions about managing cancer risks and childbearing considerations. Decisions become more complicated when women face disclosing their mutation and risk-reduction options to a romantic partner. This study identifies the concerns and perspectives of male romantic partners regarding these unique decisions. Twenty-five male participants completed an online survey posted to cancer support group message boards. Participants reported relationship changes regarding intimacy levels (n = 9), attraction (n = 2), and communication (n = 22) after mutation disclosure. Participants whose partners had not undergone prophylactic mastectomy (n = 14) reported concerns regarding sexual relations (n = 5), post-surgical appearance (n = 2), post-surgical attraction (n = 5), and health/lifespan (n = 9). Participants did not express attitude changes toward childbearing. While mutation disclosure conversations and surgical options are concerns for many BRCA mutation carriers in relationships, male partners share these concerns. Aspects of the relationship may change, but male study participants continued to support their partners. This information can benefit female BRCA mutation carriers, their current or future partners, and genetic counselors working with this particular population.
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Affiliation(s)
- Caitlin Mauer
- Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. .,UT Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390-9323, USA.
| | - Sara Spencer
- Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Jeffery Dungan
- Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Karen Hurley
- Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
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20
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Female Sexual Dysfunction. Obstet Gynecol 2015; 125:1495-1496. [DOI: 10.1097/aog.0000000000000886] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Rich TA, Liu M, Etzel CJ, Bannon SA, Mork ME, Ready K, Saraiya DS, Grubbs EG, Perrier ND, Lu KH, Arun BK, Woodard TL, Schover LR, Litton JK. Comparison of attitudes regarding preimplantation genetic diagnosis among patients with hereditary cancer syndromes. Fam Cancer 2015; 13:291-9. [PMID: 24072553 DOI: 10.1007/s10689-013-9685-0] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Preimplantation genetic diagnosis (PGD) allows couples to avoid having a child with an inherited condition, potentially reducing cancer burden in families with a hereditary cancer predisposition. This study investigated and compared awareness and acceptance of PGD among patients with different hereditary cancer syndromes. Questionnaires were mailed to 984 adults with hereditary breast and ovarian cancer, Lynch syndrome, familial adenomatous polyposis, or multiple endocrine neoplasia type 1 or 2. Associations between clinical, demographic, and psychosocial factors and awareness and acceptance of PGD were examined. Of 370 respondents (38 % return rate), 28 % felt their syndrome impacted family planning, 24 % were aware of PGD, 72 % felt that PGD should be offered, 43 % would consider using PGD, and 29 % were uncertain. Family experience and syndrome-specific characteristics, such as disease severity, quality of life and availability of medical interventions as well as gender, family planning stage, and religiosity impact perceptions of the acceptability of PGD, though a high level of uncertainty exists. Hereditary cancer patients lack awareness of PGD despite feeling that PGD should be offered, highlighting the need for education on this topic. While we found attitudes about the acceptability of PGD to be generally similar to those reported in the literature and of genetics and ethics experts, we observed similarities and differences between syndromes that provide insight into why some hereditary cancer patients may find PGD more acceptable than others.
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Affiliation(s)
- Thereasa A Rich
- Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA,
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22
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Cunningham J, Goldsmith L, Skirton H. The evidence base regarding the experiences of and attitudes to preimplantation genetic diagnosis in prospective parents. Midwifery 2015; 31:288-96. [DOI: 10.1016/j.midw.2014.09.010] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2014] [Revised: 09/19/2014] [Accepted: 09/27/2014] [Indexed: 11/16/2022]
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Avoir un enfant et accéder au DPN/DPI pour des femmes porteuses d’une mutation BRCA ? Malades et indemnes appréhendent la question différemment. Bull Cancer 2014; 101:1001-8. [DOI: 10.1684/bdc.2014.2036] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
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24
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Woodson AH, Muse KI, Lin H, Jackson M, Mattair DN, Schover L, Woodard T, McKenzie L, Theriault RL, Hortobágyi GN, Arun B, Peterson SK, Profato J, Litton JK. Breast cancer, BRCA mutations, and attitudes regarding pregnancy and preimplantation genetic diagnosis. Oncologist 2014; 19:797-804. [PMID: 24951607 DOI: 10.1634/theoncologist.2014-0057] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND Women with premenopausal breast cancer may face treatment-related infertility and have a higher likelihood of a BRCA mutation, which may affect their attitudes toward future childbearing. METHODS Premenopausal women were invited to participate in a questionnaire study administered before and after BRCA genetic testing. We used the Impact of Event Scale (IES) to evaluate the pre- and post-testing impact of cancer or carrying a BRCA mutation on attitudes toward future childbearing. The likelihood of pursuing prenatal diagnosis (PND) or preimplantation genetic diagnosis (PGD) was also assessed in this setting. Univariate analyses determined factors contributing to attitudes toward future childbearing and likelihood of PND or PGD. RESULTS One hundred forty-eight pretesting and 114 post-testing questionnaires were completed. Women with a personal history of breast cancer had less change in IES than those with no history of breast cancer (p = .003). The 18 BRCA-positive women had a greater change in IES than the BRCA-negative women (p = .005). After testing, 31% and 24% of women would use PND and PGD, respectively. BRCA results did not significantly affect attitudes toward PND/PGD. CONCLUSION BRCA results and history of breast cancer affect the psychological impact on future childbearing. Intentions to undergo PND or PGD do not appear to change after disclosure of BRCA results. Additional counseling for patients who have undergone BRCA testing may be warranted to educate patients about available fertility preservation options.
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Affiliation(s)
- Ashley H Woodson
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Kimberly I Muse
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Heather Lin
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Michelle Jackson
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Danielle N Mattair
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Leslie Schover
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Terri Woodard
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Laurie McKenzie
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Richard L Theriault
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Gabriel N Hortobágyi
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Banu Arun
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Susan K Peterson
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Jessica Profato
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Jennifer K Litton
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
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Quinn GP, Knapp C, Sehovic I, Ung D, Bowman M, Gonzalez L, Vadaparampil ST. Knowledge and Educational Needs about Pre-Implantation Genetic Diagnosis (PGD) among Oncology Nurses. J Clin Med 2014; 3:632-45. [PMID: 26237394 PMCID: PMC4449683 DOI: 10.3390/jcm3020632] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2014] [Revised: 05/20/2014] [Accepted: 05/22/2014] [Indexed: 12/28/2022] Open
Abstract
Preimplantation genetic diagnosis (PGD), a form of assisted reproductive technology, is a new technology with limited awareness among health care professionals and hereditary cancer families. Nurses play a key role in the care of patients and are often in an ideal position to discuss and refer patients on sensitive quality of life issues, such as PGD. Two hundred and one nurses at Moffitt Cancer Center (MCC) responded to an online survey assessing knowledge and educational needs regarding PGD and families with hereditary cancer. The majority of respondents were female (n = 188), white (n = 175), had an RN/BSN degree (n = 83), and provided outpatient care at the cancer center (n = 102). More than half of respondents (78%) were unfamiliar with PGD prior to the survey and respondents who had heard of PGD had limited knowledge. More than half of the participants reported PGD was an acceptable option for families with hereditary cancer syndromes and thought individuals with a strong family or personal history should be provided with information about PGD. This study indicates that oncology nurses may benefit from and desire education about PGD. With advances in reproductive technology and options, further PGD education is needed among healthcare professionals. An examination of current oncology nursing curriculum and competencies regarding genetic education may identify need for future revisions and updates.
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Affiliation(s)
- Gwendolyn P Quinn
- Department of Oncologic Sciences, Morsani College of Medicine, University of South Florida, 12901 Bruce B Downs Blvd #11, Tampa, FL 33612, USA.
- Department of Health Outcomes & Behavior, H. Lee Moffitt Cancer Center and Research Institute, Moffitt Cancer Center, MRC CANCONT, 12902 Magnolia Drive, Tampa, FL 33612, USA.
| | - Caprice Knapp
- Department of Health Outcomes and Policy, University of Florida, 1329 SW 16th St., Gainesville, FL 32608, USA.
| | - Ivana Sehovic
- Department of Health Outcomes & Behavior, H. Lee Moffitt Cancer Center and Research Institute, Moffitt Cancer Center, MRC CANCONT, 12902 Magnolia Drive, Tampa, FL 33612, USA.
| | - Danielle Ung
- Department of Health Outcomes & Behavior, H. Lee Moffitt Cancer Center and Research Institute, Moffitt Cancer Center, MRC CANCONT, 12902 Magnolia Drive, Tampa, FL 33612, USA.
| | - Meghan Bowman
- Department of Health Outcomes & Behavior, H. Lee Moffitt Cancer Center and Research Institute, Moffitt Cancer Center, MRC CANCONT, 12902 Magnolia Drive, Tampa, FL 33612, USA.
| | - Luis Gonzalez
- Department of Health Outcomes & Behavior, H. Lee Moffitt Cancer Center and Research Institute, Moffitt Cancer Center, MRC CANCONT, 12902 Magnolia Drive, Tampa, FL 33612, USA.
| | - Susan T Vadaparampil
- Department of Oncologic Sciences, Morsani College of Medicine, University of South Florida, 12901 Bruce B Downs Blvd #11, Tampa, FL 33612, USA.
- Department of Health Outcomes & Behavior, H. Lee Moffitt Cancer Center and Research Institute, Moffitt Cancer Center, MRC CANCONT, 12902 Magnolia Drive, Tampa, FL 33612, USA.
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Derks-Smeets IAP, de Die-Smulders CEM, Mackens S, van Golde R, Paulussen AD, Dreesen J, Tournaye H, Verdyck P, Tjan-Heijnen VCG, Meijer-Hoogeveen M, De Greve J, Geraedts J, De Rycke M, Bonduelle M, Verpoest WM. Hereditary breast and ovarian cancer and reproduction: an observational study on the suitability of preimplantation genetic diagnosis for both asymptomatic carriers and breast cancer survivors. Breast Cancer Res Treat 2014; 145:673-81. [DOI: 10.1007/s10549-014-2951-5] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2014] [Accepted: 04/02/2014] [Indexed: 11/28/2022]
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Abstract
In the care of patients with Lynch Syndrome (LS), a range of psychosocial issues are encountered, which significantly affect patient outcomes. A brief historical background of 'psycho-onco-genetics' (the domain where psychology, oncology and genetics meet) in relation to LS is presented, followed by an overview of important psychosocial issues identified in the past 20 years. The identification of mismatch repair genes in 1993-1994 made possible genetic counseling and testing for patients who had cancer and for potentially high-risk relatives without cancer. At that time, concerns were raised about the potentially negative psychosocial impact of predictive genetic testing. Since 1993, a large number of studies have been conducted to investigate the possible psychosocial benefits and limitations of such testing. This article presents an overview of: the uptake of and motivations for genetic testing, its psychosocial impact (e.g. psychological adaptation, impact on risk perception and self-concept, and concerns about, and experiences of, genetic discrimination), psychological screening instruments, adherence to and decision-making about preventive strategies, family communication, lifestyle changes, reproductive technology utilization, and professional psychosocial support needs of members of families with LS. Finally, challenges for the future are discussed, including population screening and genomic testing.
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28
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Derks-Smeets IAP, Gietel-Habets JJG, Tibben A, Tjan-Heijnen VCG, Meijer-Hoogeveen M, Geraedts JPM, van Golde R, Gomez-Garcia E, van den Bogaart E, van Hooijdonk M, de Die-Smulders CEM, van Osch LADM. Decision-making on preimplantation genetic diagnosis and prenatal diagnosis: a challenge for couples with hereditary breast and ovarian cancer. Hum Reprod 2014; 29:1103-12. [DOI: 10.1093/humrep/deu034] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
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Pal T, Vadaparampil ST. Genetic risk assessments in individuals at high risk for inherited breast cancer in the breast oncology care setting. Cancer Control 2013; 19:255-66. [PMID: 23037493 DOI: 10.1177/107327481201900402] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND It has become increasingly common to consider BRCA mutation status when determining optimal cancer risk management and treatment options in order to improve patient outcomes. Knowledge about the risk for hereditary cancer at or as close as possible to the time of diagnosis allows patients access to the most risk reduction options available. METHODS This paper illustrates the role of genetic risk assessment for hereditary breast cancer, using hereditary breast and ovarian cancer (HBOC) syndrome as a model due to germline mutations in the BRCA1 and BRCA2. Specifically, the value of genetic counseling and testing for HBOC across the cancer prevention and control continuum is outlined as it pertains to breast cancer. RESULTS In recognition of the importance of risk assessment for hereditary breast cancer, leading health professional organizations have developed specific guidelines and recommendations to providers for identification of women at increased risk for carrying a BRCA mutation. CONCLUSIONS Institutional efforts specific to genetic counseling and testing have resulted in the implementation of a model driven by physician recommendation as a referral system for high-risk breast cancer patients. Establishing an infrastructure to support research, education, and outreach initiatives focused on BRCA genetic counseling and testing will provide information that can improve the delivery of cancer genetics services.
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Affiliation(s)
- Tuya Pal
- Population Sciences Department of Cancer Epidemiology, Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
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31
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Dekeuwer C, Bateman S. Much more than a gene: hereditary breast and ovarian cancer, reproductive choices and family life. MEDICINE, HEALTH CARE, AND PHILOSOPHY 2013; 16:231-44. [PMID: 22048863 DOI: 10.1007/s11019-011-9361-9] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/25/2023]
Abstract
This article presents the results of a study that investigates the way in which carriers of a mutation on the BRCA1 or the BRCA2 gene, associated with a high risk of breast and ovarian cancer, make their reproductive decisions. Using semi-structured interviews, the study explored the way in which these persons reflected on the acceptability of taking the risk of transmitting this mutation to the next generation, the arguments they used in favor or against taking that risk, and in the light of these arguments, their opinion on the acceptability of preimplantation genetic diagnosis (PGD) as a reproductive option. The findings suggest that when carriers are planning to have a(nother) child, they are mainly concerned by the risk of transmitting 'much more than a gene': essentially painful experiences not only with respect to health, such as undergoing cancer surveillance or combatting one's own illness, but also with regards to family life, such as witnessing the illness and death of a close relative, encountering difficulties in finding a partner or reconsidering one's plans to have a family. As for opinions concerning the acceptability of PGD as a reproductive option, opinions about personal recourse were varied but all expressed the understanding that PGD should be made available to those persons who consider it their best option.
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Affiliation(s)
- Catherine Dekeuwer
- Faculté de Philosophie, Université Lyon 3 Jean Moulin, Institut de recherches philosophiques, Lyon, France.
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32
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Donnelly LS, Watson M, Moynihan C, Bancroft E, Evans DGR, Eeles R, Lavery S, Ormondroyd E. Reproductive decision-making in young female carriers of a BRCA mutation. Hum Reprod 2013; 28:1006-12. [PMID: 23293217 DOI: 10.1093/humrep/des441] [Citation(s) in RCA: 60] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
STUDY QUESTION How do young women, who were identified as carrying a BRCA gene mutation before they had children, approach reproductive decision-making and what are their attitudes towards reproductive genetic testing? SUMMARY ANSWER Reproductive decision-making within the context of cancer risk is complex and influenced by personal experiences of cancer. Younger women were not concerned with reproductive decision-making at the time of their genetic test; however, the impact on subsequent reproductive decision-making was considerable and left them with unanticipated dilemmas, such as having children who would be at risk of inheriting cancer predisposition, timing risk-reducing surgery and changing perceptions of responsibility. WHAT IS KNOWN ALREADY Individuals carrying gene mutations predisposing to hereditary breast/ovarian cancer have concerns about passing on the gene mutation to children. STUDY DESIGN, SIZE, DURATION Qualitative methodology and thematic analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS Data were collected through semi-structured interviews with 25 women aged 18-45 who had received a positive result for a BRCA1 or BRCA2 gene mutation while childless. MAIN RESULTS AND THE ROLE OF CHANCE Analysis revealed four central themes: (i) the impact of cancer on reproductive decision-making; (ii) motivation for genetic testing; (iii) risk management and timing of planning children; and (iv) optimism for future medical advancements. LIMITATIONS, REASONS FOR CAUTION This study explores the views of female BRCA carriers. Further research should explore the views of couples, men, and include samples with greater ethnic and social diversity. WIDER IMPLICATIONS OF THE FINDINGS This evidence highlights the need for reproductive decision-making to be addressed at the time of pretest genetic counselling. More information should be provided on reproductive options as well as counselling/support to guide women's reproductive decision-making and prenatal testing options at the time they undertake genetic testing. STUDY FUNDING/COMPETING INTEREST(S) This research was supported by Cancer Research UK (Number C1226 A7920) and NIHR support to the Biomedical Research Centre at The Institute of Cancer Research and RMH. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER Not applicable.
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Affiliation(s)
- L S Donnelly
- Nightingale Centre and Genesis Prevention Centre, University Hospital of South Manchester, Manchester, UK
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Quinn GP, Pal T, Murphy D, Vadaparampil ST, Kumar A. High-risk consumers' perceptions of preimplantation genetic diagnosis for hereditary cancers: a systematic review and meta-analysis. Genet Med 2012; 14:191-200. [PMID: 22261755 DOI: 10.1038/gim.0b013e31822ddc7e] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Individuals carrying deleterious germline mutations placing them at increased risk for hereditary cancer syndromes (high-risk consumers) often have a great deal of fear and concern over transmitting mutations to their offspring, particularly conditions which are autosomal dominant. Preimplantation genetic diagnosis (PGD) is a procedure that can detect certain germline cancer predisposing mutations present in embryos. The objective of this review was to assess high-risk consumers' knowledge and perceptions of PGD for hereditary cancers. A systematic literature review was conducted through PubMed, Wiley Interscience, PsychInfo, and Cochrane Library databases to identify all articles assessing consumer knowledge and attitudes of PGD for hereditary cancer syndromes. We assessed heterogeneity and the robustness of findings through additional analyses according to study location, hereditary cancer type, and sample size. Thirteen articles remained eligible after the application of specific criteria. Results show a general low level of knowledge about PGD for hereditary cancers, moderate rates of acceptability among high-risk groups, and high levels of need for information about PGD. Individuals in specific risk groups such as those with a personal or family history of hereditary breast and ovarian cancer (HBOC) syndrome or familial adenomatous polyposis (FAP) may benefit from educational information from healthcare professionals about the use of PGD.
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Affiliation(s)
- Gwendolyn P Quinn
- Division of Cancer Prevention and Control, Moffitt Cancer Center, Tampa, Florida, USA.
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Preimplantation genetic diagnosis for hereditary cancers. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2012; 732:103-13. [PMID: 22210255 DOI: 10.1007/978-94-007-2492-1_8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/12/2023]
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BRCA1/2 carriers: their childbearing plans and theoretical intentions about having preimplantation genetic diagnosis and prenatal diagnosis. Genet Med 2012; 14:527-34. [PMID: 22241105 PMCID: PMC4088944 DOI: 10.1038/gim.2011.27] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Purpose: To assess the impact of BRCA1/2 test results on carriers' reproductive decision-making and the factors determining their theoretical intentions about preimplantation genetic diagnosis (PGD) and prenatal diagnosis (PND). Methods: Unaffected BRCA1/2 mutation carriers of childbearing age (N = 605; 449 women; 151 men) were included at least 1 year after the disclosure of their test results in a cross-sectional survey nested in a national cohort. Multivariate adjustment was performed on the data obtained in self-administered questionnaires. Results: Response rate was 81.0%. Overall, 32.5% and 50% said that they would undergo PGD/PND, respectively, at a theoretical next pregnancy, whereas only 12.1% found termination of pregnancy (TOP) acceptable. Theoretical intentions toward PGD did not depend on gender/age, but were higher among those with no future childbearing plans (adjusted odds ratio (AOR) 95% confidence interval (CI): 3.5 (1.9–6.4)) and those having fewer relatives with cancer (AOR 1.5 95% CI (1.0–2.3)). Greater TOP acceptability was observed among males and those with lower educational levels; 85.4% of respondents agreed that information about PGD/PND should be systematically delivered with the test results. Conclusions: The closer to reproductive decision-making BRCA1/2 carriers are, i.e., when they are more likely to be making future reproductive plans, the less frequently they intend to have PGD. Carriers' theoretical intentions toward PND are discussed further.
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Kurian AW, Munoz DF, Rust P, Schackmann EA, Smith M, Clarke L, Mills MA, Plevritis SK. Online tool to guide decisions for BRCA1/2 mutation carriers. J Clin Oncol 2012; 30:497-506. [PMID: 22231042 DOI: 10.1200/jco.2011.38.6060] [Citation(s) in RCA: 64] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
PURPOSE Women with BRCA1 or BRCA2 (BRCA1/2) mutations must choose between prophylactic surgeries and screening to manage their high risks of breast and ovarian cancer, comparing options in terms of cancer incidence, survival, and quality of life. A clinical decision tool could guide these complex choices. METHODS We built a Monte Carlo model for BRCA1/2 mutation carriers, simulating breast screening with annual mammography plus magnetic resonance imaging (MRI) from ages 25 to 69 years and prophylactic mastectomy (PM) and/or prophylactic oophorectomy (PO) at various ages. Modeled outcomes were cancer incidence, tumor features that shape treatment recommendations, overall survival, and cause-specific mortality. We adapted the model into an online tool to support shared decision making. RESULTS We compared strategies on cancer incidence and survival to age 70 years; for example, PO plus PM at age 25 years optimizes both outcomes (incidence, 4% to 11%; survival, 80% to 83%), whereas PO at age 40 years plus MRI screening offers less effective prevention, yet similar survival (incidence, 36% to 57%; survival, 74% to 80%). To characterize patients' treatment and survivorship experiences, we reported the tumor features and treatments associated with risk-reducing interventions; for example, in most BRCA2 mutation carriers (81%), MRI screening diagnoses stage I, hormone receptor-positive breast cancers, which may not require chemotherapy. CONCLUSION Cancer risk-reducing options for BRCA1/2 mutation carriers vary in their impact on cancer incidence, recommended treatments, quality of life, and survival. To guide decisions informed by multiple health outcomes, we provide an online tool for joint use by patients with their physicians (http://brcatool.stanford.edu).
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Ormondroyd E, Donnelly L, Moynihan C, Savona C, Bancroft E, Evans DG, Eeles R, Lavery S, Watson M. Attitudes to reproductive genetic testing in women who had a positive BRCA test before having children: a qualitative analysis. Eur J Hum Genet 2012; 20:4-10. [PMID: 21811309 PMCID: PMC3234514 DOI: 10.1038/ejhg.2011.146] [Citation(s) in RCA: 60] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2011] [Revised: 05/25/2011] [Accepted: 06/28/2011] [Indexed: 12/24/2022] Open
Abstract
The scope of conditions for which preimplantation genetic diagnosis (PGD) is licensed has recently been expanded in the United Kingdom to include genetic predisposition to adult-onset cancer. This qualitative interview study explores reproductive decision making, knowledge of and attitudes to reproductive genetic testing (prenatal diagnosis and PGD) with 25 women aged 18-45 years who received a positive BRCA test in the United Kingdom before having children. In this cohort of younger women, BRCA testing was motivated by risk management decisions; for some, BRCA status has affected their later decisions about having children. The perceived severity of hereditary breast/ovarian cancer (HBOC) influences thoughts about passing on the mutation to children and willingness to consider reproductive genetic testing, but most participants do not believe HBOC is a condition for which pregnancy termination is justified. PGD is considered more acceptable and advantageous because it would prevent transmission to future generations, but women have concerns about selecting embryos and the fact that they and affected family members would not have been selected. Women would also be deterred by the need to undergo in vitro fertilisation (IVF) and ovarian stimulation for PGD. Awareness of reproductive testing options was very variable among the cohort. The findings highlight the complexities of reproductive decision making for young women who knowingly carry a BRCA mutation, and the dilemmas inherent to reproductive genetic testing when the condition being tested for also affects a prospective parent. Counselling and psychological support for BRCA-positive women and couples concerning reproductive options are strongly indicated.
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Quinn GP, Vadaparampil ST, Miree CA, Lee JH, Zhao X, Friedman S, Yi S, Mayer J. High risk men's perceptions of pre-implantation genetic diagnosis for hereditary breast and ovarian cancer. Hum Reprod 2010; 25:2543-50. [PMID: 20713415 DOI: 10.1093/humrep/deq207] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
BACKGROUND Pre-implantation genetic diagnosis (PGD) is an assisted reproductive technology procedure which provides parents with the option of conducting genetic analyses to determine if a mutation is present in an embryo. Though studies have discussed perceptions of PGD from a general population, couples or high-risk women, no studies to date have specifically examined PGD usage among men. This study sought to explore perceptions and attitudes towards PGD among males who either carry a BRCA mutation or have a partner or first degree relative with a BRCA mutation. METHODS A cross-sectional survey was conducted among 228 men visiting the Facing Our Risk of Cancer Empowered or Craigslist website. Eligibility criteria included men who self-reported they had been tested for a BRCA mutation or had a partner or first degree relative tested for a BRCA mutation. A 41-item survey assessed socio-demographic, clinical characteristics, PGD knowledge and attitudinal factors and consideration of the use of PGD. Differences in proportions of subgroups were tested using the Monte Carlo exact test for categorical data. A multiple logistic regression model was then built through a backward elimination procedure. RESULTS Although 80% of men reported being previously unfamiliar with PGD, after learning the definition of PGD, 34% of the 228 respondents then said they would 'ever consider the use of PGD'. Respondents who thought of PGD only in terms of 'health and safety' were almost three times more likely (OR = 2.82; 95% 1.19-6.71) to 'ever consider the use of PGD' compared with respondents who thought of PGD in terms of both 'health and safety', and 'religion and morality'. CONCLUSIONS As with other anonymous web-based surveys, we cannot verify clinical characteristics that may impact consideration of PGD use. Our findings indicate high-risk men need more information about PGD and may benefit from educational materials to assist them in reproductive decision-making.
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Affiliation(s)
- Gwendolyn P Quinn
- Department of Health Outcomes & Behavior, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33613, USA.
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Hulvat MC, Jeruss JS. Maintaining fertility in young women with breast cancer. Curr Treat Options Oncol 2010; 10:308-17. [PMID: 20238254 DOI: 10.1007/s11864-010-0116-2] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
OPINION STATEMENT Breast cancer effects nearly 200,000 American women each year, with 9% of these women still in their childbearing years. For this subset of future survivors, the issue of fertility may be a significant quality-of-life concern. Both the causes and treatments for infertility in young breast cancer patients must be thoroughly understood by the multidisciplinary team caring for these women in order for the caregivers to be effective advocates for their patients. Radiation, cytotoxic chemotherapy, and hormonal therapy all effect ovarian function to greater or lesser degrees, with the incidence of permanent post-treatment amenorrhea following systemic treatment for breast cancer in women age 50 or younger estimated as between 33% and 76%. The science of fertility preservation continues to experience significant advances in terms of the success of oocyte, embryo, and ovarian tissue preservation, and it is crucial that physicians and patients are aware of the available fertility preservation options. The optimal time to address the possibility of treatment-related infertility and strategies to combat this with younger patients is prior to treatment, rather than after cancer therapy has begun, and a full knowledge of the available technologies is a prerequisite for an informed discussion. Causes of ovarian suppression and options for treatment, including consideration of preimplantation genetic diagnosis and alternative parenting approaches are also discussed to assist the clinician caring for young patients with cancer.
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Affiliation(s)
- Melissa C Hulvat
- Department of Surgery, Northwestern University Feinberg School of Medicine, 303 East Superior Street, Lurie, 4-115, Chicago, IL 60611, USA
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Allen TL, Van Groningen BJ, Barksdale DJ, McCarthy R. The Breast Self-Examination Controversy: What Providers and Patients Should Know. J Nurse Pract 2010. [DOI: 10.1016/j.nurpra.2009.11.005] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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Quinn GP, Vadaparampil ST, Tollin S, Miree CA, Murphy D, Bower B, Silva C. BRCA carriers' thoughts on risk management in relation to preimplantation genetic diagnosis and childbearing: when too many choices are just as difficult as none. Fertil Steril 2010; 94:2473-5. [PMID: 20447630 DOI: 10.1016/j.fertnstert.2010.03.064] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2009] [Revised: 03/05/2010] [Accepted: 03/24/2010] [Indexed: 12/28/2022]
Abstract
Women with a BRCA mutation have unique concerns about childbearing and future fertility. In a focus group conducted among unaffected carriers, the majority of women held positive attitudes toward preimplantation genetic diagnosis to reduce transmission to future offspring and further identified unmet needs for education and support for decision making.
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Affiliation(s)
- Gwendolyn P Quinn
- Health Outcomes and Behavior Program, Division of Population Sciences, Moffitt Cancer Center, Department of Oncologic Science, College of Medicine, University of South Florida, Tampa, Florida 33612, USA.
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42
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Factors associated with preimplantation genetic diagnosis acceptance among women concerned about hereditary breast and ovarian cancer. Genet Med 2009; 11:757-65. [PMID: 19710615 DOI: 10.1097/gim.0b013e3181b3f451] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
PURPOSE To assess sociodemographic, clinical, awareness, and attitudinal factors associated with acceptance of preimplantation genetic diagnosis among women concerned about hereditary breast and ovarian cancer. METHODS Participants (n = 962) were members of a national advocacy organization dedicated to empowering women at high risk for developing breast or ovarian cancer. Participants completed a web-based survey assessing factors associated with preimplantation genetic diagnosis acceptance. Factors significantly associated with acceptance in the bivariate analyses were used to build a logistic regression model. RESULTS Among the 962 respondents, 318 (33.1%) selected the option that they would consider preimplantation genetic diagnosis, 367 (38.2%) would not consider preimplantation genetic diagnosis, and 277 (28.8%) selected "don't know." Significant predictors of preimplantation genetic diagnosis acceptance were the desire to have more children, having had a prenatal genetic test, preimplantation genetic diagnosis awareness, belief that preimplantation genetic diagnosis is acceptable for individuals at risk for hereditary breast and ovarian cancer, belief that preimplantation genetic diagnosis information should be given to individuals at risk for hereditary breast and ovarian cancer, concerns about preimplantation genetic diagnosis, perceived benefits of preimplantation genetic diagnosis, and how preimplantation genetic diagnosis is considered. CONCLUSION Women at increased risk for hereditary cancer may consider preimplantation genetic diagnosis as part of their reproductive decision making. Therefore, it is important to understand existing levels of awareness and attitudes toward this technology to provide optimal counseling and support.
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Kurian AW, Sigal BM, Plevritis SK. Survival analysis of cancer risk reduction strategies for BRCA1/2 mutation carriers. J Clin Oncol 2009; 28:222-31. [PMID: 19996031 DOI: 10.1200/jco.2009.22.7991] [Citation(s) in RCA: 159] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
PURPOSE Women with BRCA1/2 mutations inherit high risks of breast and ovarian cancer; options to reduce cancer mortality include prophylactic surgery or breast screening, but their efficacy has never been empirically compared. We used decision analysis to simulate risk-reducing strategies in BRCA1/2 mutation carriers and to compare resulting survival probability and causes of death. METHODS We developed a Monte Carlo model of breast screening with annual mammography plus magnetic resonance imaging (MRI) from ages 25 to 69 years, prophylactic mastectomy (PM) at various ages, and/or prophylactic oophorectomy (PO) at ages 40 or 50 years in 25-year-old BRCA1/2 mutation carriers. RESULTS With no intervention, survival probability by age 70 is 53% for BRCA1 and 71% for BRCA2 mutation carriers. The most effective single intervention for BRCA1 mutation carriers is PO at age 40, yielding a 15% absolute survival gain; for BRCA2 mutation carriers, the most effective single intervention is PM, yielding a 7% survival gain if performed at age 40 years. The combination of PM and PO at age 40 improves survival more than any single intervention, yielding 24% survival gain for BRCA1 and 11% for BRCA2 mutation carriers. PM at age 25 instead of age 40 offers minimal incremental benefit (1% to 2%); substituting screening for PM yields a similarly minimal decrement in survival (2% to 3%). CONCLUSION Although PM at age 25 plus PO at age 40 years maximizes survival probability, substituting mammography plus MRI screening for PM seems to offer comparable survival. These results may guide women with BRCA1/2 mutations in their choices between prophylactic surgery and breast screening.
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Affiliation(s)
- Allison W Kurian
- Departments of Medicine, Health Research and Policy, and Radiology, Stanford University School of Medicine, Stanford, CA, USA
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44
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Attitudes toward genetic testing in childhood and reproductive decision-making for familial adenomatous polyposis. Eur J Hum Genet 2009; 18:186-93. [PMID: 19809485 DOI: 10.1038/ejhg.2009.151] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
Abstract
Childhood DNA testing, prenatal diagnosis (PND) and preimplantation genetic diagnosis (PGD) are available for familial adenomatous polyposis (FAP). However, the use of PND and PGD is controversial. The purpose of this study was to investigate attitudes toward, and experiences with, childhood DNA testing, PND and PGD among members of families at high risk for FAP. In this nationwide, cross-sectional study, questionnaires were sent to individuals from families at high risk for FAP assessing attitudes toward and experiences with childhood testing, PND and PGD, as well as several sociodemographic, clinical and psychosocial variables. Of the individuals from FAP families invited to participate in the study, 525 members participated (response rate=64%). Most parents who had children who were minors (n=93) (82%) were satisfied with the DNA testing procedure. One-third of all individuals wanted DNA testing for their children before age 12. Forty percent of FAP patients indicated that the disease influenced their desire to have children. Only 15% considered termination of pregnancy for FAP acceptable. Approximately 30% of individuals with a FAP diagnosis and their partners considered PND and PGD as acceptable for themselves. A positive attitude was associated with higher levels of guilt and a positive attitude toward termination of pregnancy. Importantly, of those with FAP at childbearing age, 84% had had no previous information at all about either PND or PGD. Future efforts should be aimed at educating FAP family members about reproductive options, allowing them to make an informed choice about family planning. Routine discussion of all reproductive options with a medical specialist should be encouraged.
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Sagi M, Weinberg N, Eilat A, Aizenman E, Werner M, Girsh E, Siminovsky Y, Abeliovich D, Peretz T, Simon A, Laufer N. Preimplantation genetic diagnosis for BRCA1/2--a novel clinical experience. Prenat Diagn 2009; 29:508-13. [PMID: 19248143 DOI: 10.1002/pd.2232] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
OBJECTIVE To describe our 2-year experience with preimplantation genetic diagnosis (PGD) for carriers of mutations in the genes BRCA1 and BRCA2, the dilemmas incurred and the lessons learned. METHODS We collected data on those carriers of BRCA1/2 mutations who applied for PGD counseling and who decided to proceed. We describe the PGD procedures that were conducted and their outcome. RESULTS Ten carriers of BRCA1/2 mutations applied for PGD counseling, seven were healthy, and three were BC survivors. Eight women needed in vitro fertilization (IVF) because of coexisting infertility. After counseling, six opted for the procedure and five of them underwent PGD for the BRCA mutation. In one of these PGD, fluorescence in situ hybridization (FISH) analysis for chromosomes 21, X and Y was also performed. Three women conceived, each in the first treatment attempt. One of them gave birth to twins, the second to a singleton and the third is currently pregnant. During the pregnancies, dilemmas concerning PGD confirmation were discussed. CONCLUSIONS PGD is an acceptable reproductive option for BRCA mutation carriers, especially for those who require IVF due to fertility problems. Discussion of this option should be carried out with sensitivity, taking into account the age of the woman, her health, fertility status and emotional state. Confirmatory prenatal diagnosis may not always be encouraged.
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Affiliation(s)
- M Sagi
- Department of Human Genetics, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
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Clancy T. A clinical perspective on ethical arguments around prenatal diagnosis and preimplantation genetic diagnosis for later onset inherited cancer predispositions. Fam Cancer 2009; 9:9-14. [PMID: 19644768 DOI: 10.1007/s10689-009-9271-7] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2009] [Accepted: 07/16/2009] [Indexed: 11/30/2022]
Abstract
Prenatal diagnosis (PND) and preimplantation genetic diagnosis (PGD) for later onset and/or reduced penetrance inherited cancer predispositions, e.g. familial adenomatous polyposis, hereditary non-polyposis colorectal cancer/Lynch syndrome and hereditary breast and ovarian cancer, raise a number of ethical issues. Some of these are the same as for conditions which present early in childhood, are fully penetrant and for which no/limited treatment options are possible; others relate to whether reduced penetrance and/or the availability of treatment mean that these are not serious (enough) conditions to warrant tests prior to/during pregnancy or to justify termination of pregnancy. However, attempts to reach a consensus on what counts as a serious (enough) condition in the context of PND and PGD have been unsuccessful. Such a definition may anyway be unhelpful if it cannot also take into account, for example, the woman's/couple's awareness and experience of the condition and the impact of the condition on affected individuals and their families. Individuals affected by, or at high risk of, later onset and/or reduced penetrance inherited cancer predispositions are generally supportive of access to PND and PGD for their own conditions, even if they would not consider using it themselves. Professionals working in clinical cancer genetics need to be prepared to discuss PND and PGD with this group of patients.
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Affiliation(s)
- Tara Clancy
- Genetic Medicine, Manchester Academic Health Sciences Centre, Central Manchester University Hospitals NHS Foundation Trust, St Mary's Hospital, Oxford Road, Manchester, M13 9WL, UK.
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Lammens C, Bleiker E, Aaronson N, Vriends A, Ausems M, Jansweijer M, Wagner A, Sijmons R, van den Ouweland A, van der Luijt R, Spruijt L, Gómez García E, Ruijs M, Verhoef S. Attitude towards pre-implantation genetic diagnosis for hereditary cancer. Fam Cancer 2009; 8:457-64. [PMID: 19642022 PMCID: PMC2771132 DOI: 10.1007/s10689-009-9265-5] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2009] [Accepted: 06/30/2009] [Indexed: 12/31/2022]
Abstract
The use of pre-implantation genetic diagnosis (PGD) for hereditary cancer is subject to on-going debate, particularly among professionals. This study evaluates the attitude towards PGD and attitude-associated characteristics of those concerned: family members with a hereditary cancer predisposition. Forty-eight Von Hippel-Lindau and 18 Li–Fraumeni Syndrome families were identified via the 9 family cancer clinics in the Netherlands. In total, 216 high risk family members and partners were approached, of whom 179 (83%) completed a self-report questionnaire. Of the high risk family members, 35% expressed a positive attitude towards PGD. Those with a current desire to have children were significantly more likely to have a positive attitude: 48% would consider the use of PGD. No other sociodemographic, medical or psychosocial variables were associated significantly with a positive attitude. The most frequently reported advantage of PGD is the avoidance of a possible pregnancy termination. Uncertainty about late effects was the most frequently reported disadvantage. These results indicate that approximately half of those contemplating a future pregnancy would consider the use of PGD. The actual uptake, however, is expected to be lower. There is no indication that psychosocial factors affect interest in PGD.
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Affiliation(s)
- Chantal Lammens
- Division of Psychosocial Research & Epidemiology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
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Conflict between values and technology: perceptions of preimplantation genetic diagnosis among women at increased risk for hereditary breast and ovarian cancer. Fam Cancer 2009; 8:441-9. [PMID: 19554475 DOI: 10.1007/s10689-009-9263-7] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2008] [Accepted: 06/09/2009] [Indexed: 10/20/2022]
Abstract
Members of families affected by hereditary cancer are often concerned about passing on risk to offspring. Preimplantation genetic diagnosis is a procedure performed to identify embryos that inherit mutations placing them at risk for hereditary conditions. Little is known about attitudes toward the use of this technology among individuals at risk for hereditary breast and ovarian cancer. We sought to determine high risk women's attitudes. This study is a qualitative examination of comments from women who participated in an online survey regarding knowledge and attitudes of preimplantation genetic diagnosis among individuals affected by hereditary breast and ovarian cancer. More than half the respondents held less favorable attitudes about the use of preimplantation genetic diagnosis for hereditary breast and ovarian cancer for both themselves and others. However, among the women who felt favorable about its usage, the majority said it became a new option for them to pursue parenthood whereas previously they had opted to not have a biological child. The high percentage of respondents who have never heard of preimplantation genetic diagnosis and who were in favor of this technology for hereditary breast and ovarian cancer indicates the need for educational campaigns to increase awareness and provide information about the procedure, access and affordability. Further research is needed to determine how this population would like this information presented to them and how best to instruct health care professionals to present this topic to women who do not know to ask about it.
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