Risk-Reducing Bilateral Salpingo-Oophorectomy for Ovarian Cancer: A Review and Clinical Guide for Hereditary Predisposition Genes
Pathogenic germline variants underlie up to 20% of ovarian cancer (OC) and are associated with varying degrees of risk for OC. For mutations in high-penetrance genes such as / , the role of risk-reducing bilateral salpingo-oophorectomy (RRSO) in cancer prevention is well-established and improves mor...
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| Vydáno v: | JCO oncology practice Ročník 18; číslo 3; s. 201 |
|---|---|
| Hlavní autoři: | , , , , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
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United States
01.03.2022
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| ISSN: | 2688-1535, 2688-1535 |
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| Abstract | Pathogenic germline variants underlie up to 20% of ovarian cancer (OC) and are associated with varying degrees of risk for OC. For mutations in high-penetrance genes such as
/
, the role of risk-reducing bilateral salpingo-oophorectomy (RRSO) in cancer prevention is well-established and improves mortality. However, in moderate-penetrance genes where the degree of risk for OC is less precisely defined, the role of RRSO is more controversial. Although national guidelines have evolved to incorporate gene-specific recommendations, studies demonstrate significant variations in practice. Given this, our multidisciplinary group has reviewed the available literature on risk estimates for genes associated with OC, incorporated levels of evidence, and set thresholds for consideration of RRSO. We found that the benefit of RRSO is well-established for pathogenic variants in
/2 as well as
and
/
where the risk of OC is elevated beyond our threshold for RRSO. In
, RRSO is particularly controversial as newer studies consistently demonstrate an increased risk of OC that is dependent on family history, making uniform recommendations challenging. Additionally, new guidelines for Lynch syndrome provide gene-specific risks, questioning the role of RRSO, and even hysterectomy, for
and
mutation carriers. Given these uncertainties, shared decision making should be used around RRSO with discussion of individual risk factors, family history, and adverse effects of surgery and premature menopause. Herein, we provide a clinical guide and counseling points. |
|---|---|
| AbstractList | Pathogenic germline variants underlie up to 20% of ovarian cancer (OC) and are associated with varying degrees of risk for OC. For mutations in high-penetrance genes such as BRCA1/2, the role of risk-reducing bilateral salpingo-oophorectomy (RRSO) in cancer prevention is well-established and improves mortality. However, in moderate-penetrance genes where the degree of risk for OC is less precisely defined, the role of RRSO is more controversial. Although national guidelines have evolved to incorporate gene-specific recommendations, studies demonstrate significant variations in practice. Given this, our multidisciplinary group has reviewed the available literature on risk estimates for genes associated with OC, incorporated levels of evidence, and set thresholds for consideration of RRSO. We found that the benefit of RRSO is well-established for pathogenic variants in BRCA1/2 as well as BRIP1 and RAD51C/D where the risk of OC is elevated beyond our threshold for RRSO. In PALB2, RRSO is particularly controversial as newer studies consistently demonstrate an increased risk of OC that is dependent on family history, making uniform recommendations challenging. Additionally, new guidelines for Lynch syndrome provide gene-specific risks, questioning the role of RRSO, and even hysterectomy, for MSH6 and PMS2 mutation carriers. Given these uncertainties, shared decision making should be used around RRSO with discussion of individual risk factors, family history, and adverse effects of surgery and premature menopause. Herein, we provide a clinical guide and counseling points.Pathogenic germline variants underlie up to 20% of ovarian cancer (OC) and are associated with varying degrees of risk for OC. For mutations in high-penetrance genes such as BRCA1/2, the role of risk-reducing bilateral salpingo-oophorectomy (RRSO) in cancer prevention is well-established and improves mortality. However, in moderate-penetrance genes where the degree of risk for OC is less precisely defined, the role of RRSO is more controversial. Although national guidelines have evolved to incorporate gene-specific recommendations, studies demonstrate significant variations in practice. Given this, our multidisciplinary group has reviewed the available literature on risk estimates for genes associated with OC, incorporated levels of evidence, and set thresholds for consideration of RRSO. We found that the benefit of RRSO is well-established for pathogenic variants in BRCA1/2 as well as BRIP1 and RAD51C/D where the risk of OC is elevated beyond our threshold for RRSO. In PALB2, RRSO is particularly controversial as newer studies consistently demonstrate an increased risk of OC that is dependent on family history, making uniform recommendations challenging. Additionally, new guidelines for Lynch syndrome provide gene-specific risks, questioning the role of RRSO, and even hysterectomy, for MSH6 and PMS2 mutation carriers. Given these uncertainties, shared decision making should be used around RRSO with discussion of individual risk factors, family history, and adverse effects of surgery and premature menopause. Herein, we provide a clinical guide and counseling points. Pathogenic germline variants underlie up to 20% of ovarian cancer (OC) and are associated with varying degrees of risk for OC. For mutations in high-penetrance genes such as / , the role of risk-reducing bilateral salpingo-oophorectomy (RRSO) in cancer prevention is well-established and improves mortality. However, in moderate-penetrance genes where the degree of risk for OC is less precisely defined, the role of RRSO is more controversial. Although national guidelines have evolved to incorporate gene-specific recommendations, studies demonstrate significant variations in practice. Given this, our multidisciplinary group has reviewed the available literature on risk estimates for genes associated with OC, incorporated levels of evidence, and set thresholds for consideration of RRSO. We found that the benefit of RRSO is well-established for pathogenic variants in /2 as well as and / where the risk of OC is elevated beyond our threshold for RRSO. In , RRSO is particularly controversial as newer studies consistently demonstrate an increased risk of OC that is dependent on family history, making uniform recommendations challenging. Additionally, new guidelines for Lynch syndrome provide gene-specific risks, questioning the role of RRSO, and even hysterectomy, for and mutation carriers. Given these uncertainties, shared decision making should be used around RRSO with discussion of individual risk factors, family history, and adverse effects of surgery and premature menopause. Herein, we provide a clinical guide and counseling points. |
| Author | Liu, Ying L Grisham, Rachel N Latham, Alicia Offit, Kenneth Frey, Melissa K Breen, Kelsey Abu-Rustum, Nadeem Aghajanian, Carol Catchings, Amanda Ranganathan, Megha Goldfrank, Deborah J Chi, Dennis S Long Roche, Kara Stadler, Zsofia K |
| Author_xml | – sequence: 1 givenname: Ying L orcidid: 0000-0001-5790-851X surname: Liu fullname: Liu, Ying L organization: Department of Medicine, Weill Cornell Medical College of Cornell University, New York, NY – sequence: 2 givenname: Kelsey orcidid: 0000-0001-7302-1564 surname: Breen fullname: Breen, Kelsey organization: Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY – sequence: 3 givenname: Amanda orcidid: 0000-0002-6005-4778 surname: Catchings fullname: Catchings, Amanda organization: Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY – sequence: 4 givenname: Megha orcidid: 0000-0002-3245-8812 surname: Ranganathan fullname: Ranganathan, Megha organization: Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY – sequence: 5 givenname: Alicia orcidid: 0000-0002-9758-713X surname: Latham fullname: Latham, Alicia organization: General Internal Medicine, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY – sequence: 6 givenname: Deborah J surname: Goldfrank fullname: Goldfrank, Deborah J organization: Department of Obstetrics and Gynecology, Weill Cornell Medical College of Cornell University, New York, NY – sequence: 7 givenname: Rachel N surname: Grisham fullname: Grisham, Rachel N organization: Department of Medicine, Weill Cornell Medical College of Cornell University, New York, NY – sequence: 8 givenname: Kara surname: Long Roche fullname: Long Roche, Kara organization: Department of Obstetrics and Gynecology, Weill Cornell Medical College of Cornell University, New York, NY – sequence: 9 givenname: Melissa K orcidid: 0000-0002-6705-1211 surname: Frey fullname: Frey, Melissa K organization: Department of Obstetrics and Gynecology, Weill Cornell Medical College of Cornell University, New York, NY – sequence: 10 givenname: Dennis S surname: Chi fullname: Chi, Dennis S organization: Department of Obstetrics and Gynecology, Weill Cornell Medical College of Cornell University, New York, NY – sequence: 11 givenname: Nadeem surname: Abu-Rustum fullname: Abu-Rustum, Nadeem organization: Department of Obstetrics and Gynecology, Weill Cornell Medical College of Cornell University, New York, NY – sequence: 12 givenname: Carol surname: Aghajanian fullname: Aghajanian, Carol organization: Department of Medicine, Weill Cornell Medical College of Cornell University, New York, NY – sequence: 13 givenname: Kenneth orcidid: 0000-0002-2180-2032 surname: Offit fullname: Offit, Kenneth organization: Department of Medicine, Weill Cornell Medical College of Cornell University, New York, NY – sequence: 14 givenname: Zsofia K orcidid: 0000-0002-6985-2864 surname: Stadler fullname: Stadler, Zsofia K organization: Department of Medicine, Weill Cornell Medical College of Cornell University, New York, NY |
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| SubjectTerms | Female Genetic Predisposition to Disease Humans Mutation Ovarian Neoplasms - genetics Ovarian Neoplasms - prevention & control Ovarian Neoplasms - surgery Risk Factors Salpingo-oophorectomy |
| Title | Risk-Reducing Bilateral Salpingo-Oophorectomy for Ovarian Cancer: A Review and Clinical Guide for Hereditary Predisposition Genes |
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