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Pennington KP, Pugh SL, Huh W, Walker JL, Jewell E, Havrilesky LJ, Carter J, Muller CY, Drapkin R, Lankes HA, Castellano T, Zamorano AS, Blank SV, Kachnic LA. Optimization of Timing for Risk-Reducing Salpingectomy and Oophorectomy. Obstet Gynecol 2025; 145:21-30. [PMID: 39509704 PMCID: PMC11637911 DOI: 10.1097/aog.0000000000005781] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Accepted: 09/26/2024] [Indexed: 11/15/2024]
Abstract
CLINICAL TRIAL REGISTRATION ClinicalTrials.gov , NCT04251052.
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Affiliation(s)
- Kathryn P Pennington
- Alaska Women's Cancer Care, Anchorage, Alaska; the NRG Oncology Statistics and Data Management Center, the University of Pennsylvania, and NRG Oncology Philadelphia East, Philadelphia, Pennsylvania; the University of Alabama Birmingham Cancer Center, Birmingham, Alabama; the University of Oklahoma, Oklahoma City, Oklahoma; Memorial Sloan Kettering Cancer Center, Icahn School of Medicine at Mount Sinai, and Columbia University Medical Center, MU-NCORP, New York, New York; Duke University Medical Center, Durham, North Carolina; the University of New Mexico Health Sciences Center, Albuquerque, New Mexico; The Ohio State University Wexner Medical Center, Columbus, Ohio; the Louisiana State University Health Science Center, New Orleans, Louisiana; and the University of Texas Health Science Center at Houston/McGovern Medical School, Houston, Texas
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Jordano JO, Gallion T, Cevan C, Carew B, Lloyd MC, Weaver EO, Miller RF, Dudek M. How the other half screens: A model for partnerships between student-run free clinics and genetic counseling programs to address disparities in hereditary cancer evaluation. J Genet Couns 2024; 33:1136-1144. [PMID: 37960965 DOI: 10.1002/jgc4.1835] [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: 05/18/2023] [Revised: 10/19/2023] [Accepted: 10/26/2023] [Indexed: 11/15/2023]
Abstract
Genetic medicine is considered a major part of the future of preventative care, offering evidence-based, effective interventions to improve health outcomes and reduce morbidity and mortality, especially regarding hereditary cancer screening. Identification of individuals who would benefit from screening is key to improving their cancer-related healthcare outcomes. However, patients without insurance, of historically underserved races, of lower socioeconomic status, and in rural communities have lower access to such care. Barriers to access lead to populations having higher rates of undetected hereditary cancer, and consequently more severe forms of cancer. With an already-established reach, student-run free clinics can work with genetic counseling training programs to incorporate genetic medicine into their workflow. Such partnerships will (1) make genetic care more accessible with goals of improving patient morbidity, mortality, and health outcomes, (2) offer robust educational experiences for genetic counseling learners, particularly in understanding social determinants of health and barriers to care, and (3) actively combat the growing racial and geographic gaps in genetic care. Our study presents how one student-run free clinic implemented genetic counseling into its primary care workflow to improve access to genetics services. We present two examples of how genetic counseling improved patients' medical care. We also identify obstacles encountered during this program's development, as well as solutions-those we incorporated and possible considerations for other clinics. With the hope that other clinics can use this paper to design similar partnerships, we aim to lessen the gap between sickness and screening.
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Affiliation(s)
- James O Jordano
- Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
- Medical Degree Program, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
| | - Tielle Gallion
- Master of Genetic Counseling Program, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
| | - Chloe Cevan
- Master of Genetic Counseling Program, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
| | - Babatunde Carew
- Section of General Internal Medicine and Public Health, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - M Cooper Lloyd
- Section of General Internal Medicine and Public Health, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Eleanor O Weaver
- Section of General Internal Medicine and Public Health, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Robert F Miller
- Section of General Internal Medicine and Public Health, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Martha Dudek
- Master of Genetic Counseling Program, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
- Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, Tennessee, USA
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Holtzman S, McCarthy L, Estevez SL, Lee JA, Baird MF, Gounko D, Copperman AB, Blank SV. Walking the tightrope: Fertility preservation among hereditary breast and ovarian Cancer syndrome Previvors. Gynecol Oncol 2024; 186:176-181. [PMID: 38696905 DOI: 10.1016/j.ygyno.2024.03.025] [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: 01/03/2024] [Revised: 03/21/2024] [Accepted: 03/26/2024] [Indexed: 05/04/2024]
Abstract
INTRODUCTION Fertility-related concerns cause significant anxiety among patients with Hereditary Breast and Ovarian Cancer Syndrome (HBOC). The Society of Gynecologic Oncology and the American Society for Reproductive Medicine recommend patients diagnosed with HBOC receive early referral to a reproductive endocrinologist. However, evidence about fertility trends in this patient population are limited and guidelines are scarce. The aim of this study is to compare fertility preservation among patients with HBOC to control patients undergoing fertility treatment without a diagnosis of infertility. METHODS This retrospective study included patients who presented to a single academic institution for fertility preservation in the setting of diagnosis of HBOC. In this study, HBOC patients are referred to as those who had tested positive for pathogenic mutations in BRCA1, BRCA2 or were at high-risk for HBOC based on a strong family history (defined as >3 family members diagnosed with HBOC) without a genetic mutation. HBOC patients were matched in a 1:1 fashion to a control group undergoing fertility preservation without a diagnosis of infertility or HBOC. All analysis was done using SPSS version 9.4 (SAS Institute, Cary, NC). RESULTS Between August 1st, 2016 and August 1st, 2022, 81 patients presented to the study center for consultation in the setting of HBOC. Of those who presented, 48 (59.2%) ultimately underwent oocyte cryopreservation and 33 (40.7%) underwent embryo cryopreservation. Patients who underwent oocyte cryopreservation due to BRCA1 status were more likely to present for fertility consultation at a younger age compared to control patients (32.6 vs. 34.7 years, p = 0.03) and were more likely to undergo oocyte cryopreservation at a younger age (32.1 vs. 34.6 years, p = 0.007). There was no difference in age at initial consultation or age at procedure for patients with BRCA2 or patients with a strong family history compared to control patients (p > 0.05). There was no difference in the mean age of patients with HBOC at presentation for consultation for embryo cryopreservation or the mean age the patient with HBOC underwent embryo cryopreservation compared to control patients (p > 0.05). Patients with BRCA1 or BRCA2 did not have expedited time from consultation to first cycle start (p > 0.05). After adjusting for factors including anti-Müllerian hormone (AMH) level and age, patients considered in the HBOC group due to family history had less time between consultation and oocyte cryopreservation cycle compared to control patients. (179 vs. 317 days, p = 0.045). There was no difference in time from consultation to starting cycle for embryo cryopreservation for patients with HBOC compared to controls (p > 0.05). CONCLUSION Patients with HBOC did not undergo expedited fertility treatment compared to control patients undergoing oocyte and embryo cryopreservation for non-infertility reasons. Patients diagnosed with BRCA1 had more oocytes retrieved compared to the control population which is possibly due to earlier age of presentation in the setting of recommended age of risk reducing surgery being age 35-40. When age matched, cycle outcomes did not differ between HBOC and control patients. Given the known cancer prevention benefit and recommendations for risk-reducing surgery, future studies should focus on guidelines for fertility preservation for patients with HBOC.
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Affiliation(s)
- Sharonne Holtzman
- Icahn School of Medicine at the Mount Sinai Department of Obstetrics, Gynecology, and Reproductive Science, New York, NY, USA.
| | - Lily McCarthy
- Icahn School of Medicine at the Mount Sinai Department of Obstetrics, Gynecology, and Reproductive Science, New York, NY, USA
| | - Samantha L Estevez
- Icahn School of Medicine at the Mount Sinai Department of Obstetrics, Gynecology, and Reproductive Science, New York, NY, USA; Reproductive Medicine Associates of New York, New York, NY, USA
| | - Joseph A Lee
- Reproductive Medicine Associates of New York, New York, NY, USA
| | - Morgan F Baird
- Reproductive Medicine Associates of New York, New York, NY, USA
| | - Dmitry Gounko
- Reproductive Medicine Associates of New York, New York, NY, USA
| | - Alan B Copperman
- Icahn School of Medicine at the Mount Sinai Department of Obstetrics, Gynecology, and Reproductive Science, New York, NY, USA; Reproductive Medicine Associates of New York, New York, NY, USA
| | - Stephanie V Blank
- Icahn School of Medicine at the Mount Sinai Department of Obstetrics, Gynecology, and Reproductive Science, New York, NY, USA
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Kim J, Choi CH. Basic knowledge for counseling patients undergoing risk-reducing salpingo-oophorectomy. Obstet Gynecol Sci 2024; 67:343-355. [PMID: 38817104 PMCID: PMC11266848 DOI: 10.5468/ogs.24054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2024] [Revised: 05/09/2024] [Accepted: 05/23/2024] [Indexed: 06/01/2024] Open
Abstract
Significant progress has been made in the molecular diagnosis of cancer. It provides personalized medicine, including cancer diagnosis, prognosis, targeted therapy, and risk detection. These advances allow physicians to identify patients at risk for cancer before it develops and offer them an opportunity to prevent its development. Mutations in breast cancer susceptibility genes 1 and 2 (BRCA1 and 2) are one of the most well-known cancer-related gene mutations since actor Angelina Jolie shared her experience with genetic mutations and risk-reducing surgery in the media. In Korea, tests for germline BRCA1/2 mutations have been covered by insurance since May 2012 and the number of women of BRCA1/2 mutations has continued to increase over the past decade. Most carriers of BRCA1/2 mutations consider risk-reducing salpingo-oophorectomy (RRSO) resulting in early menopause and want to know the lifetime risks and benefits of RRSO. However, despite the increasing number of carriers of BRCA1/2 mutations, the counseling and management of patients requiring RRSO varies among physicians. This article provides basic knowledge on RRSO to help physicians comprehensively assess its risks and benefits and manage at-risk women.
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Affiliation(s)
- Jihye Kim
- Department of Obstetrics and Gynecology, Chung-Ang University Gwangmyeong Hospital, Gwangmyeong, Korea
| | - Chel Hun Choi
- Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Jandoubi N, Boujemaa M, Mighri N, Mejri N, Ben Nasr S, Bouaziz H, Berrazega Y, Rachdi H, Daoud N, Zribi A, Ayari J, El Benna H, Labidi S, Haddaoui A, Mrad R, Ben Ahmed S, Boussen H, Abdelhak S, Boubaker S, Hamdi Y. Genetic testing for hereditary cancer syndromes in Tunisian patients: Impact on health system. Transl Oncol 2024; 43:101912. [PMID: 38387387 PMCID: PMC10900923 DOI: 10.1016/j.tranon.2024.101912] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Revised: 01/29/2024] [Accepted: 02/12/2024] [Indexed: 02/24/2024] Open
Abstract
INTRODUCTION Cancer management in Africa faces diverse challenges due to limited resources, health system challenges, and other matters. Identifying hereditary cancer syndromic cases is crucial to improve clinical management and preventive care in these settings. This study aims to explore the clinicopathological features and genetic factors associated with hereditary cancer in Tunisia, a North African country with a rising cancer burden MATERIALS AND METHODS: Clinicopathological features and personal/family history of cancer were explored in 521 patients. Genetic analysis using Sanger and next-generation sequencing was performed for a set of patients RESULTS: Hereditary breast and ovarian cancer syndrome was the most frequent cluster in which 36 BRCA mutations were identified. We described a subgroup of patients with likely ''breast cancer-only syndrome'' among this cluster. Two cases of Li-Fraumeni syndrome with distinct TP53 mutations namely c.638G>A and c.733G>A have been identified. Genetic investigation also allowed the identification of a new BLM homozygous mutation (c.3254dupT) in one patient with multiple primary cancers. Phenotype-genotype correlation suggests the diagnosis of Bloom syndrome. A recurrent MUTYH mutation (c.1143_1144dup) was identified in three patients with different phenotypes CONCLUSION: Our study calls for comprehensive genetic education and the implementation of genetic screening in Tunisia and other African countries health systems, to reduce the burden of hereditary diseases and improve cancer outcomes in resource-stratified settings.
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Affiliation(s)
- Nouha Jandoubi
- Laboratory of Biomedical Genomics and Oncogenetics, LR20IPT05, Institut Pasteur de Tunis, University of Tunis El Manar, Tunis, Tunisia
| | - Maroua Boujemaa
- Laboratory of Biomedical Genomics and Oncogenetics, LR20IPT05, Institut Pasteur de Tunis, University of Tunis El Manar, Tunis, Tunisia
| | - Najah Mighri
- Laboratory of Biomedical Genomics and Oncogenetics, LR20IPT05, Institut Pasteur de Tunis, University of Tunis El Manar, Tunis, Tunisia
| | - Nesrine Mejri
- Laboratory of Biomedical Genomics and Oncogenetics, LR20IPT05, Institut Pasteur de Tunis, University of Tunis El Manar, Tunis, Tunisia; Medical Oncology Department, Abderrahman Mami Hospital, Faculty of Medicine Tunis, University Tunis El Manar, Tunis, Tunisia
| | - Sonia Ben Nasr
- Laboratory of Biomedical Genomics and Oncogenetics, LR20IPT05, Institut Pasteur de Tunis, University of Tunis El Manar, Tunis, Tunisia; Department of Medical Oncology, Military Hospital of Tunis, Tunis, Tunisia
| | - Hanen Bouaziz
- Laboratory of Biomedical Genomics and Oncogenetics, LR20IPT05, Institut Pasteur de Tunis, University of Tunis El Manar, Tunis, Tunisia; Surgical Oncology Department, Salah Azaiez Institute of Cancer, Tunis, Tunisia
| | - Yosra Berrazega
- Medical Oncology Department, Abderrahman Mami Hospital, Faculty of Medicine Tunis, University Tunis El Manar, Tunis, Tunisia
| | - Haifa Rachdi
- Medical Oncology Department, Abderrahman Mami Hospital, Faculty of Medicine Tunis, University Tunis El Manar, Tunis, Tunisia
| | - Nouha Daoud
- Medical Oncology Department, Abderrahman Mami Hospital, Faculty of Medicine Tunis, University Tunis El Manar, Tunis, Tunisia
| | - Aref Zribi
- Department of Medical Oncology, Military Hospital of Tunis, Tunis, Tunisia
| | - Jihene Ayari
- Department of Medical Oncology, Military Hospital of Tunis, Tunis, Tunisia
| | - Houda El Benna
- Laboratory of Biomedical Genomics and Oncogenetics, LR20IPT05, Institut Pasteur de Tunis, University of Tunis El Manar, Tunis, Tunisia; Medical Oncology Department, Abderrahman Mami Hospital, Faculty of Medicine Tunis, University Tunis El Manar, Tunis, Tunisia
| | - Soumaya Labidi
- Laboratory of Biomedical Genomics and Oncogenetics, LR20IPT05, Institut Pasteur de Tunis, University of Tunis El Manar, Tunis, Tunisia; Medical Oncology Department, Abderrahman Mami Hospital, Faculty of Medicine Tunis, University Tunis El Manar, Tunis, Tunisia
| | | | - Ridha Mrad
- Department of Human Genetics, Charles Nicolle Hospital, Tunis, Tunisia
| | - Slim Ben Ahmed
- Department of Medical Oncology, Farhat Hached University Hospital of Sousse, Faculty of Medicine of Sousse, Tunisia
| | - Hamouda Boussen
- Laboratory of Biomedical Genomics and Oncogenetics, LR20IPT05, Institut Pasteur de Tunis, University of Tunis El Manar, Tunis, Tunisia; Medical Oncology Department, Abderrahman Mami Hospital, Faculty of Medicine Tunis, University Tunis El Manar, Tunis, Tunisia
| | - Sonia Abdelhak
- Laboratory of Biomedical Genomics and Oncogenetics, LR20IPT05, Institut Pasteur de Tunis, University of Tunis El Manar, Tunis, Tunisia
| | - Samir Boubaker
- Laboratory of Biomedical Genomics and Oncogenetics, LR20IPT05, Institut Pasteur de Tunis, University of Tunis El Manar, Tunis, Tunisia; Laboratory of Human and Experimental Pathology, Institut Pasteur de Tunis, Tunis, Tunisia
| | - Yosr Hamdi
- Laboratory of Biomedical Genomics and Oncogenetics, LR20IPT05, Institut Pasteur de Tunis, University of Tunis El Manar, Tunis, Tunisia; Laboratory of Human and Experimental Pathology, Institut Pasteur de Tunis, Tunis, Tunisia.
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Sia TY, Maio A, Kemel YM, Arora KS, Gordhandas SB, Kahn RM, Salo-Mullen EE, Sheehan MA, Tejada PR, Bandlamudi C, Zhou Q, Iasonos A, Grisham RN, O'Cearbhaill RE, Tew WP, Roche KL, Zivanovic O, Sonoda Y, Gardner GJ, Chi DS, Latham AJ, Carlo MI, Murciano-Goroff YR, Will M, Walsh MF, Robson ME, Mandelker DL, Berger MF, Abu-Rustum NR, Brown CL, Offit K, Hamilton JG, Aghajanian C, Weigelt B, Stadler ZK, Liu YL. Germline Pathogenic Variants and Genetic Counseling by Ancestry in Patients With Epithelial Ovarian Cancer. JCO Precis Oncol 2023; 7:e2300137. [PMID: 37738546 PMCID: PMC10861001 DOI: 10.1200/po.23.00137] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2023] [Revised: 05/11/2023] [Accepted: 07/17/2023] [Indexed: 09/24/2023] Open
Abstract
PURPOSE To evaluate rates of germline pathogenic/likely pathogenic variants (PVs) and genetic counseling by ancestry in patients with epithelial ovarian cancer (EOC). METHODS Patients with pathologically confirmed EOC who underwent clinical tumor-normal sequencing from January 1, 2015, to December 31, 2020, inclusive of germline analysis of ≥76 genes were included. Patients with newly identified PVs were referred for Clinical Genetics Service (CGS) counseling. Ancestry groups were defined using self-reported race/ethnicity and Ashkenazi Jewish (AJ) heritage. Genetic ancestry was inferred computationally using validated algorithms. Logistic regression models were built. RESULTS Of 1,266 patients, self-reported ancestry (AJ, 17%; Asian, 10%; Black/African American, 5.4%; Hispanic, 6.2%; non-Hispanic White, 57%; other, 0.16%; unknown, 4.0%) correlated with genetic ancestry (AJ ancestry, 18%; admixed, 10%; African, 4%; East Asian [EAS], 6%; European, 56%; Native American, 0.2%; South Asian [SAS], 4%; unknown, 2%). Germline PVs were observed in 313 (25%) patients, including 195 (15%) with PVs in EOC-associated genes. Those with PVs were younger at diagnosis (59 v 62 years; P < .001) and more likely to have high-grade serous ovarian cancer (83% v 72%; P = .009). PV prevalence varied between ancestry groups (P < .001), with highest rates in the AJ (39.9%) and Asian (26.5%) groups and similar rates (>10%) across other ancestry groups. Use of genetic ancestry demonstrated similar findings and further characterized high rates of PV in EAS/SAS groups. Younger age, high-grade serous histology, and self-reported AJ or Asian ancestry were associated with PV in an EOC-associated gene. Rates of CGS counseling for newly identified PVs were high (80%) across ancestry groups. CONCLUSION Rates of PV, particularly in EOC-associated genes, were high regardless of ancestry, with similar rates of counseling between groups, emphasizing the importance of universal genetic testing in all patients with EOC.
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Affiliation(s)
- Tiffany Y. Sia
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Anna Maio
- Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Yelena M. Kemel
- Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Kanika S. Arora
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Sushmita B. Gordhandas
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Ryan M. Kahn
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Erin E. Salo-Mullen
- Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Margaret A. Sheehan
- Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Prince Rainier Tejada
- Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Chaitanya Bandlamudi
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Qin Zhou
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Alexia Iasonos
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Rachel N. Grisham
- Gynecologic Medical Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
- Department of Medicine, Weill Cornell Medical College, New York, NY
| | - Roisin E. O'Cearbhaill
- Gynecologic Medical Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
- Department of Medicine, Weill Cornell Medical College, New York, NY
| | - William P. Tew
- Gynecologic Medical Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
- Department of Medicine, Weill Cornell Medical College, New York, NY
| | - Kara Long Roche
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
- Department of Obstetrics and Gynecology, Weill Cornell Medical College, New York, NY
| | - Oliver Zivanovic
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
- Department of Obstetrics and Gynecology, Weill Cornell Medical College, New York, NY
| | - Yukio Sonoda
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
- Department of Obstetrics and Gynecology, Weill Cornell Medical College, New York, NY
| | - Ginger J. Gardner
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
- Department of Obstetrics and Gynecology, Weill Cornell Medical College, New York, NY
| | - Dennis S. Chi
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
- Department of Obstetrics and Gynecology, Weill Cornell Medical College, New York, NY
| | - Alicia J. Latham
- Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
- Department of Medicine, Weill Cornell Medical College, New York, NY
| | - Maria I. Carlo
- Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
- Department of Medicine, Weill Cornell Medical College, New York, NY
| | - Yonina R. Murciano-Goroff
- Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
- Department of Medicine, Weill Cornell Medical College, New York, NY
| | - Marie Will
- Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
- Department of Medicine, Weill Cornell Medical College, New York, NY
| | - Michael F. Walsh
- Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
- Department of Medicine, Weill Cornell Medical College, New York, NY
| | - Mark E. Robson
- Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
- Department of Medicine, Weill Cornell Medical College, New York, NY
| | - Diana L. Mandelker
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Michael F. Berger
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Nadeem R. Abu-Rustum
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
- Department of Obstetrics and Gynecology, Weill Cornell Medical College, New York, NY
| | - Carol L. Brown
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
- Department of Obstetrics and Gynecology, Weill Cornell Medical College, New York, NY
| | - Kenneth Offit
- Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
- Department of Medicine, Weill Cornell Medical College, New York, NY
| | - Jada G. Hamilton
- Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
- Department of Psychiatry, Weill Cornell Medical College, New York, NY
- Department of Psychiatry and Behavioral Sciences, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Carol Aghajanian
- Gynecologic Medical Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
- Department of Medicine, Weill Cornell Medical College, New York, NY
| | - Britta Weigelt
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Zsofia K. Stadler
- Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
- Department of Medicine, Weill Cornell Medical College, New York, NY
| | - Ying L. Liu
- Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
- Gynecologic Medical Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
- Department of Medicine, Weill Cornell Medical College, New York, NY
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Harris CJ, Rowell EE, Jayasinghe Y, Cost C, Childress KJ, Frederick NN, McNally O, Appiah L, Anazodo A. Pediatric, adolescent, and young adult breast and reproductive tumors. Pediatr Blood Cancer 2023; 70 Suppl 5:e29422. [PMID: 36458682 DOI: 10.1002/pbc.29422] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Revised: 08/03/2021] [Accepted: 08/17/2021] [Indexed: 12/04/2022]
Abstract
Tumors of the breast and reproductive organs that occur in children, adolescents, and young adults (AYA) have different biological features and can present special challenges. Although prognosis for these tumors is generally favorable, the long-term effects of treatment can be debilitating. Treatments are often multimodal and may include surgery as well as chemotherapy and/or radiation, which can cause considerable distress and anxiety related to loss of femininity or masculinity, concern over future fertility, or sexual dysfunction. Thus, tumors of the reproductive organs in pediatric/AYA patients require special consideration of the treatment effects beyond the intended oncologic outcome. Multidisciplinary teams should be involved in their care and address issues of fertility, sexual dysfunction, and psychosexual concerns before treatment begins. This review addresses histology, risk factors, prognosis, staging and treatment of gynecologic, breast and testicular cancers in pediatric and AYA patients.
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Affiliation(s)
- Courtney J Harris
- Ann & Robert H Lurie Children's Hospital of Chicago, Chicago, Illinois
| | - Erin E Rowell
- Ann & Robert H Lurie Children's Hospital of Chicago, Chicago, Illinois
| | - Yasmin Jayasinghe
- Royal Women's Hospital, Parkville, Victoria, Australia
- Royal Children's Hospital, Parkville, Victoria, Australia
- University of Melbourne, Parkville, Victoria, Australia
| | - Carrye Cost
- Children's Hospital Colorado, Aurora, Colorado
| | - Krista J Childress
- Children's Healthcare of Atlanta, Atlanta, Georgia
- Emory University, Atlanta, Georgia
| | - Natasha N Frederick
- Department of Pediatrics and the Center for Cancer and Blood Disorders, Connecticut Children's Medical Center, Hartford, Connecticut
- University of Connecticut School of Medicine, Farmington, Connecticut
| | - Orla McNally
- Royal Women's Hospital, Parkville, Victoria, Australia
- University of Melbourne, Parkville, Victoria, Australia
| | | | - Antoinette Anazodo
- Sydney Children's Hospital, Sydney, New South Wales, Australia
- Prince of Wales Hospital, Sydney, New South Wales, Australia
- School of Women's and Children's, University of New South Wales, High St Kensington, New South Wales, Australia
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Byun JM, Cho HJ, Lee DS, Yoon HK, Kim YN, Im DH, Kim DH, Lee KB, Sung MS, Jeong DH. Frequency of serous tubal intraepithelial carcinoma (STIC) in patients with high grade serous ovarian cancer. Taiwan J Obstet Gynecol 2023; 62:107-111. [PMID: 36720520 DOI: 10.1016/j.tjog.2022.09.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/14/2022] [Indexed: 01/30/2023] Open
Abstract
OBJECTIVE Serous tubal intraepithelial carcinoma (STIC) is a known precursor of high-grade serous ovarian cancer (HGSOC). This study aimed to evaluate the proportion of STIC in patients with HGSOC and analyze the STIC-related prognosis in patients with HGSOC. MATERIALS AND METHODS All pathology reports at our institution that included bilateral salpingectomies of patients with HGSOC from January 2013 to December 2018 were reviewed by two experienced pathologists. The specimens from the ovaries and the salpinx including fimbria were examined. We analyzed the correlation between STIC and HGSOC and compared the clinical characteristics and STIC-related prognostic outcomes in patients with HGSOC. RESULTS Eleven of the 76 cases were STIC. BRCA mutations were found in 16.9% of patients with HGSOC. STIC was observed in 30.0% of patients with BRCA mutations and in 14.3% of patients without BRCA mutations. The incidence of STIC in patients with BRCA mutations was approximately twice that in patients without BRCA mutations; however, the difference was not statistically significant (P = 0.231). Further, the 5-year survival rate of patients without STIC appeared to be high; nevertheless, the difference was not statistically significant (59.7% vs. 47.4%, P = 0.633). Moreover, there was no significant difference in disease-free survival rate according to STIC (36.4% vs. 33.1%, P = 0.956). CONCLUSION STIC was identified in patients with HGSOC, and STIC incidence was prominent in HGSOC related to BRCA mutation. Although low frequency, STIC was detected in patients without BRCA mutation. Therefore, prophylactic salpingectomy may be useful for prevention of HGSOC.
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Affiliation(s)
- Jung Mi Byun
- Department of Obstetrics and Gynecology, Busan Paik Hospital, Inje University, College of Medicine, South Korea; Paik Institute for Clinical Research, Inje University, College of Medicine, South Korea.
| | - Hwa Jin Cho
- Department of Pathology, Inje University, College of Medicine, South Korea
| | - Dae Sim Lee
- Department of Obstetrics and Gynecology, Busan Paik Hospital, Inje University, College of Medicine, South Korea; Paik Institute for Clinical Research, Inje University, College of Medicine, South Korea
| | - Hye Kyoung Yoon
- Department of Pathology, Inje University, College of Medicine, South Korea
| | - Young Nam Kim
- Department of Obstetrics and Gynecology, Busan Paik Hospital, Inje University, College of Medicine, South Korea; Paik Institute for Clinical Research, Inje University, College of Medicine, South Korea
| | - Do Hwa Im
- Department of Obstetrics and Gynecology, Busan Paik Hospital, Inje University, College of Medicine, South Korea
| | - Da Hyun Kim
- Department of Obstetrics and Gynecology, Busan Paik Hospital, Inje University, College of Medicine, South Korea
| | - Kyung Bok Lee
- Department of Obstetrics and Gynecology, Busan Paik Hospital, Inje University, College of Medicine, South Korea; Paik Institute for Clinical Research, Inje University, College of Medicine, South Korea
| | - Moon Su Sung
- Department of Obstetrics and Gynecology, Busan Paik Hospital, Inje University, College of Medicine, South Korea; Paik Institute for Clinical Research, Inje University, College of Medicine, South Korea
| | - Dae Hoon Jeong
- Department of Obstetrics and Gynecology, Busan Paik Hospital, Inje University, College of Medicine, South Korea; Paik Institute for Clinical Research, Inje University, College of Medicine, South Korea.
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9
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Tumors of the Female Reproductive Organs. Fam Med 2022. [DOI: 10.1007/978-3-030-54441-6_112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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10
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Sekine M, Enomoto T, Arai M, Den H, Nomura H, Ikeuchi T, Nakamura S. Differences in age at diagnosis of ovarian cancer for each BRCA mutation type in Japan: optimal timing to carry out risk-reducing salpingo-oophorectomy. J Gynecol Oncol 2022; 33:e46. [PMID: 35557031 PMCID: PMC9250856 DOI: 10.3802/jgo.2022.33.e46] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2021] [Revised: 12/10/2021] [Accepted: 03/05/2022] [Indexed: 12/04/2022] Open
Abstract
Objective BRCA1 and BRCA2 mutation carriers are recommended to undergo risk-reducing salpingo-oophorectomy (RRSO) by age 40 and 45, respectively. However, the carriers have a different way of thinking about their life plan. We aimed to investigate the distribution of age at diagnosis of ovarian cancer (OC) patients to examine the optimal timing of RRSO in the carriers. Methods We examined a correlation between age at diagnosis of OC and common mutation types in 3,517 probands that received BRCA genetic testing. Among them, germline BRCA1 mutation (gBRCA1m), germline BRCA2 mutation (gBRCA2m) and germline BRCA wild-type (gBRCAwt) were found in 185, 42 and 241 OC patients, respectively. Results The average age at diagnosis of OC in gBRCA1m and gBRCA2m was 51.3 and 58.3 years, respectively, and the difference from gBRCAwt (53.8 years) was significant. The gBRCA2m carriers did not develop OC under the age of 40. The average age was 50.1 years for L63X and 52.8 years for Q934X in BRCA1, and 55.1 years for R2318X and 61.1 years for STOP1861 in BRCA2. The age at diagnosis in L63X or R2318X carriers was relatively younger than other BRCA1 or BRCA2 carriers, however their differences were not significant. With L63X and R2318X carriers, 89.4% (42/47) and 100% (7/7) of women were able to prevent the development of OC, respectively, when RRSO was performed at age 40. Conclusion There appears to be no difference in the age at diagnosis of OC depending on the type of BRCA common mutation. Further analysis would be needed. This is the first report to present the optimal timing of risk-reducing salpingo-oophorectomy for each BRCA mutation type in Japan. The average age at diagnosis of ovarian cancer (OC) in germline BRCA2 mutation (gBRCA2m) is higher than that in germline BRCA wild-type. The gBRCA2m carriers did not develop OC under the age of 40. The average age at diagnosis in L63X or R2318X carriers was relatively younger than other BRCA mutation carriers, though the differences were not significant.
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Affiliation(s)
- Masayuki Sekine
- Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Takayuki Enomoto
- Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Masami Arai
- Clinical Genetics, Juntendo University, Graduate School of Medicine, Tokyo, Japan
| | - Hiroki Den
- Department of Hygiene, Public Health, and Preventative Medicine, Showa University School of Medicine, Tokyo, Japan
| | - Hiroyuki Nomura
- Department of Obstetrics and Gynecology, School of Medicine, Fujita Health University, Toyoake, Japan
| | - Takeshi Ikeuchi
- Department of Molecular Genetics, Brain Research Institute, Niigata University, Niigata, Japan
| | - Seigo Nakamura
- Division of Breast Surgical Oncology, Department of Surgery, Showa University School of Medicine, Tokyo, Japan
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11
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Chichura A, Hunt J, Lang J, Pederson H. Lapses in breast cancer screening for highly penetrant mutation carriers during pregnancy and lactation. J Surg Oncol 2021; 125:589-595. [PMID: 34855221 DOI: 10.1002/jso.26761] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2021] [Revised: 11/10/2021] [Accepted: 11/13/2021] [Indexed: 11/05/2022]
Abstract
BACKGROUND AND OBJECTIVES Screening for breast cancer in highly penetrant mutation carriers during pregnancy and lactation is challenging and consensus guidelines are lacking. This study evaluates the lapse in screening and the interval pregnancy-associated breast cancer rate. METHODS A single-institution retrospective cohort study of pregnant and lactating patients with known pathogenic germline mutations was performed. Lapse in screening was defined as the interval between the last screening imaging exam obtained before last menstrual period and the subsequent screening imaging. RESULTS Out of 685 patients, 42 had 1-3 evaluable pregnancies (54 total - 28 managed in High Risk Breast Clinic and 26 by OB/GYN). Mutations were observed in patients in BRCA1 (49%), BRCA2 (36%), CDH1 (5%), CHEK2 (2%), ATM (2%), NF1 (3%), and MSH2 (3%). The average screening lapse was 25 [19, 30] months for patients followed in the High Risk Clinic versus 32.5 [21, 65.75] months for patients followed with Routine Care (p = 0.035). We identified three cases of pregnancy-associated breast cancer (interval cancer rate 6%). CONCLUSIONS Patients with highly penetrant mutations are at risk for the development of interval pregnancy-associated breast cancer. Development of consistent screening guidelines and adherence to those guidelines is needed for this patient population.
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Affiliation(s)
- Anna Chichura
- Department of Obstetrics, Gynecology, and Women's Health, Obstetrics, Gynecology, Women's Health Institute, Cleveland Clinic, Cleveland, Ohio, USA.,Department of Surgery, NorthShore University Health System, Evanston, Illinois, USA.,Department of Surgery, Pritzker School of Medicine, University of Chicago, Chicago, Illinois, USA
| | - Jonathan Hunt
- Department of Obstetrics, Gynecology, and Women's Health, Obstetrics, Gynecology, Women's Health Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Julie Lang
- Division of Breast Surgery, Department of General Surgery, Cleveland Clinic, Cleveland, Ohio, USA
| | - Holly Pederson
- Breast Center, Departments of General Surgery and Genomic Medicine Institute, Cleveland Clinic, Cleveland, Ohio, USA
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12
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Shen L, Zhang S, Wang K, Wang X. Familial Breast Cancer: Disease Related Gene Mutations and Screening Strategies for Chinese Population. Front Oncol 2021; 11:740227. [PMID: 34926254 PMCID: PMC8671637 DOI: 10.3389/fonc.2021.740227] [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: 07/12/2021] [Accepted: 11/12/2021] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND About 5%-10% of the breast cancer cases have a hereditary background, and this subset is referred to as familial breast cancer (FBC). In this review, we summarize the susceptibility genes and genetic syndromes associated with FBC and discuss the FBC screening and high-risk patient consulting strategies for the Chinese population. METHODS We searched the PubMed database for articles published between January 2000 and August 2021. Finally, 380 pieces of literature addressing the genes and genetic syndromes related to FBC were included and reviewed. RESULTS We identified 16 FBC-related genes and divided them into three types (high-, medium-, and low-penetrance) of genes according to their relative risk ratios. In addition, six genetic syndromes were found to be associated with FBC. We then summarized the currently available screening strategies for FBC and discussed those available for high-risk Chinese populations. CONCLUSION Multiple gene mutations and genetic disorders are closely related to FBC. The National Comprehensive Cancer Network (NCCN) guidelines recommend corresponding screening strategies for these genetic diseases. However, such guidelines for the Chinese population are still lacking. For screening high-risk groups in the Chinese population, genetic testing is recommended after genetic counseling.
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Affiliation(s)
| | | | | | - Xiaochen Wang
- Department of Breast Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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13
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Uptake and timing of risk-reducing salpingo-oophorectomy among patients with BRCA1 and BRCA2 mutations. Am J Obstet Gynecol 2021; 225:508.e1-508.e10. [PMID: 34171390 DOI: 10.1016/j.ajog.2021.06.070] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2021] [Revised: 06/15/2021] [Accepted: 06/17/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND In women with BRCA mutations, risk-reducing bilateral salpingo-oophorectomy has been shown to decrease gynecologic cancer-specific and overall mortality. The National Comprehensive Cancer Network recommends that patients with BRCA mutations undergo risk-reducing bilateral salpingo-oophorectomy between the ages of 35 and 40 years for BRCA1 mutation carriers and between the ages of 40 and 45 years for BRCA2 mutation carriers or after childbearing is complete. Currently, uptake and timing of risk-reducing bilateral salpingo-oophorectomy and reasons for delays in risk-reducing bilateral salpingo-oophorectomy are not well understood. OBJECTIVE We sought to evaluate uptake and timing of risk-reducing bilateral salpingo-oophorectomy among women with BRCA1 and BRCA2 mutations concerning the National Comprehensive Cancer Network guidelines and reasons for delays in risk-reducing bilateral salpingo-oophorectomy. STUDY DESIGN In this retrospective chart review, we identified women with BRCA1 and BRCA2 mutations who discussed risk-reducing bilateral salpingo-oophorectomy with a provider between 2012 and 2021. Uptake of risk-reducing bilateral salpingo-oophorectomy was documented, and patients were classified as having timely or delay in risk-reducing bilateral salpingo-oophorectomy based on the National Comprehensive Cancer Network guidelines. For those with delay in risk-reducing bilateral salpingo-oophorectomy, reasons cited for delay were collected. Comparative statistical analyses were performed to evaluate characteristics of those with timely vs delayed risk-reducing bilateral salpingo-oophorectomy. A multivariable logistic regression model was used to evaluate the associations among factors related to timing of risk-reducing bilateral salpingo-oophorectomy. RESULTS We identified 638 BRCA1 and BRCA2 mutation carriers seen between 2012 and 2021. Of these patients, 306 (48.0%) had undergone risk-reducing bilateral salpingo-oophorectomy and 332 (52.0%) had not. When evaluating the timing of risk-reducing bilateral salpingo-oophorectomy, 136 (21.3%) underwent timely risk-reducing bilateral salpingo-oophorectomy, 239 (37.5%) had delays in risk-reducing bilateral salpingo-oophorectomy, and 263 (41.2%) had not undergone risk-reducing bilateral salpingo-oophorectomy but were younger than the National Comprehensive Cancer Network age guidelines; therefore, they were neither timely nor delayed. Patients with delay in risk-reducing bilateral salpingo-oophorectomy were significantly older at the time of genetic testing than those with timely risk-reducing bilateral salpingo-oophorectomy (mean, 49.8 vs 36.3 years; P<.001). Of the 306 patients who underwent risk-reducing bilateral salpingo-oophorectomy, those with delayed risk-reducing bilateral salpingo-oophorectomy had a significantly shorter interval between BRCA identification and risk-reducing bilateral salpingo-oophorectomy than those with timely risk-reducing bilateral salpingo-oophorectomy (median, 8.7 vs 17.6 months; P<.001). Patients with delay in risk-reducing bilateral salpingo-oophorectomy were more likely to have a personal history of cancer than those with timely risk-reducing bilateral salpingo-oophorectomy (49.8% vs 37.5%; P=.028). Of the 239 women with delay in risk-reducing bilateral salpingo-oophorectomy, 188 (78.7%) had delayed BRCA mutation identification, 29 (12.1%) had menopausal concerns, 17 (7.1%) had ongoing cancer treatment, 12 (5.0%) had coordination with breast surgery, 20 (8.4%) had miscellaneous reasons, and 19 (7.9%) had no reason documented. In the multivariate model, older age at BRCA diagnosis (odds ratio, 0.73; 95% confidence interval, 0.68-0.78; P<.001) was significantly associated with delayed risk-reducing bilateral salpingo-oophorectomy timing; those with BRCA2 mutation type were 7.54 times as likely to have timely risk-reducing bilateral salpingo-oophorectomy than BRCA1 mutation carriers (odds ratio, 7.54; 95% confidence, 3.70-16.42; P<.001). CONCLUSION Nearly 38% of BRCA1 and BRCA2 mutation carriers undergo or have yet to undergo risk-reducing bilateral salpingo-oophorectomy over the recommended National Comprehensive Cancer Network age. The most common reason for the delay in risk-reducing bilateral salpingo-oophorectomy was delayed identification of BRCA mutation, noted in 79% of patients with delayed risk-reducing bilateral salpingo-oophorectomy. Timely genetic testing for eligible patients can increase appropriately timed risk-reducing bilateral salpingo-oophorectomy for the prevention of ovarian cancer and reduction of mortality in BRCA mutation carriers.
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14
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Sekine M, Nishino K, Enomoto T. Differences in Ovarian and Other Cancers Risks by Population and BRCA Mutation Location. Genes (Basel) 2021; 12:genes12071050. [PMID: 34356066 PMCID: PMC8303997 DOI: 10.3390/genes12071050] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Revised: 07/02/2021] [Accepted: 07/06/2021] [Indexed: 12/24/2022] Open
Abstract
Hereditary breast and ovarian cancer is caused by a germline mutation in BRCA1 or BRCA2 genes. The frequency of germline BRCA1/2 gene mutation carriers and the ratio of germline BRCA1 to BRCA2 mutations in BRCA-related cancer patients vary depending on the population. Genotype and phenotype correlations have been reported in BRCA mutant families, however, the correlations are rarely used for individual risk assessment and management. BRCA genetic testing has become a companion diagnostic for PARP inhibitors, and the number of families with germline BRCA mutation identified is growing rapidly. Therefore, it is expected that analysis of the risk of developing cancer will be possible in a large number of BRCA mutant carriers, and there is a possibility that personal and precision medicine for the carriers with specific common founder mutations will be realized. In this review, we investigated the association of ovarian cancer risk and BRCA mutation location, and differences of other BRCA-related cancer risks by BRCA1/2 mutation, and furthermore, we discussed the difference in the prevalence of germline BRCA mutation in ovarian cancer patients. As a result, although there are various discussions, there appear to be differences in ovarian cancer risk by population and BRCA mutation location. If it becomes possible to estimate the risk of developing BRCA-related cancer for each BRCA mutation type, the age at risk-reducing salpingo-oophorectomy can be determined individually. The decision would bring great benefits to young women with germline BRCA mutations.
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Affiliation(s)
- Masayuki Sekine
- Correspondence: ; Tel.: +81-25-227-2320; Fax: +81-25-227-0789
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15
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Kurian AW, Ward KC, Abrahamse P, Bondarenko I, Hamilton AS, Deapen D, Morrow M, Berek JS, Hofer TP, Katz SJ. Time Trends in Receipt of Germline Genetic Testing and Results for Women Diagnosed With Breast Cancer or Ovarian Cancer, 2012-2019. J Clin Oncol 2021; 39:1631-1640. [PMID: 33560870 PMCID: PMC8274804 DOI: 10.1200/jco.20.02785] [Citation(s) in RCA: 79] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Revised: 12/07/2020] [Accepted: 12/22/2020] [Indexed: 12/27/2022] Open
Abstract
PURPOSE Genetic testing is important for breast and ovarian cancer risk reduction and treatment, yet little is known about its evolving use. METHODS SEER records of women of age ≥ 20 years diagnosed with breast or ovarian cancer from 2013 to 2017 in California or Georgia were linked to the results of clinical germline testing through 2019. We measured testing trends, rates of variants of uncertain significance (VUS), and pathogenic variants (PVs). RESULTS One quarter (25.2%) of 187,535 patients with breast cancer and one third (34.3%) of 14,689 patients with ovarian cancer were tested; annually, testing increased by 2%, whereas the number of genes tested increased by 28%. The prevalence of test results by gene category for breast cancer cases in 2017 were BRCA1/2, PVs 5.2%, and VUS 0.8%; breast cancer-associated genes or ovarian cancer-associated genes (ATM, BARD1, BRIP1, CDH1, CHEK2, EPCAM, MLH1, MSH2, MSH6, NBN, NF1, PALB2, PMS2, PTEN, RAD51C, RAD51D, STK11, and TP53), PVs 3.7%, and VUS 12.0%; other actionable genes (APC, BMPR1A, MEN1, MUTYH, NF2, RB1, RET, SDHAF2, SDHB, SDHC, SDHD, SMAD4, TSC1, TSC2, and VHL) PVs 0.6%, and VUS 0.5%; and other genes, PVs 0.3%, and VUS 2.6%. For ovarian cancer cases in 2017, the prevalence of test results were BRCA1/2, PVs 11.0%, and VUS 0.9%; breast or ovarian genes, PVs 4.0%, and VUS 12.6%; other actionable genes, PVs 0.7%, and VUS 0.4%; and other genes, PVs 0.3%, and VUS 0.6%. VUS rates doubled over time (2013 diagnoses: 11.2%; 2017 diagnoses: 26.8%), particularly for racial or ethnic minorities (47.8% Asian and 46.0% Black, v 24.6% non-Hispanic White patients; P < .001). CONCLUSION A testing gap persists for patients with ovarian cancer (34.3% tested v nearly all recommended), whereas adding more genes widened a racial or ethnic gap in VUS results. Most PVs were in 20 breast cancer-associated genes or ovarian cancer-associated genes; testing other genes yielded mostly VUS. Quality improvement should focus on testing indicated patients rather than adding more genes.
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Affiliation(s)
- Allison W. Kurian
- Departments of Medicine and of Epidemiology & Population Health, Stanford University, Stanford, CA
| | - Kevin C. Ward
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA
| | - Paul Abrahamse
- Department of Health Management and Policy, School of Public Health, Department of Biostatistics, University of Michigan, Ann Arbor, MI
| | - Irina Bondarenko
- Department of Health Management and Policy, School of Public Health, Department of Biostatistics, University of Michigan, Ann Arbor, MI
| | - Ann S. Hamilton
- Department of Preventive Medicine in the Keck School of Medicine, University of Southern California, Los Angeles, CA
| | - Dennis Deapen
- Department of Preventive Medicine in the Keck School of Medicine, University of Southern California, Los Angeles, CA
| | - Monica Morrow
- Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY
| | - Jonathan S. Berek
- Department of Obstetrics and Gynecology and Women's Cancer Center, Stanford University, Stanford, CA
| | - Timothy P. Hofer
- Department of Internal Medicine, University of Michigan and Center for Clinical Management Research, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, MI
| | - Steven J. Katz
- Department of Health Management and Policy, School of Public Health, Department of Biostatistics, University of Michigan, Ann Arbor, MI
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Santandrea G, Piana S, Valli R, Zanelli M, Gasparini E, De Leo A, Mandato VD, Palicelli A. Immunohistochemical Biomarkers as a Surrogate of Molecular Analysis in Ovarian Carcinomas: A Review of the Literature. Diagnostics (Basel) 2021; 11:199. [PMID: 33572888 PMCID: PMC7911119 DOI: 10.3390/diagnostics11020199] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Revised: 01/26/2021] [Accepted: 01/27/2021] [Indexed: 12/27/2022] Open
Abstract
The term "ovarian carcinoma" encompasses at least five different malignant neoplasms: high-grade serous carcinoma, low-grade serous carcinoma, endometrioid carcinoma, mucinous carcinoma, and clear cell carcinoma. These five histotypes demonstrated distinctive histological, molecular, and clinical features. The rise of novel target therapies and of a tailored oncological approach has demanded an integrated multidisciplinary approach in the setting of ovarian carcinoma. The need to implement a molecular-based classification in the worldwide diagnostic and therapeutic setting of ovarian cancer demanded a search for easy-to-use and cost-effective molecular-surrogate biomarkers, relying particularly on immunohistochemical analysis. The present review focuses on the role of immunohistochemistry as a surrogate of molecular analysis in the everyday diagnostic approach to ovarian carcinomas.
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Affiliation(s)
- Giacomo Santandrea
- Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, 41121 Modena, Italy
- Pathology Unit, AUSL-IRCCS Reggio Emilia, 42123 Reggio Emilia, Italy; (S.P.); (R.V.); (M.Z.); (A.P.)
| | - Simonetta Piana
- Pathology Unit, AUSL-IRCCS Reggio Emilia, 42123 Reggio Emilia, Italy; (S.P.); (R.V.); (M.Z.); (A.P.)
| | - Riccardo Valli
- Pathology Unit, AUSL-IRCCS Reggio Emilia, 42123 Reggio Emilia, Italy; (S.P.); (R.V.); (M.Z.); (A.P.)
| | - Magda Zanelli
- Pathology Unit, AUSL-IRCCS Reggio Emilia, 42123 Reggio Emilia, Italy; (S.P.); (R.V.); (M.Z.); (A.P.)
| | - Elisa Gasparini
- Oncology Unit, AUSL-IRCCS Reggio Emilia, 42123 Reggio Emilia, Italy;
| | - Antonio De Leo
- Molecular Diagnostic Unit, AUSL Bologna, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40138 Bologna, Italy;
| | - Vincenzo Dario Mandato
- Unit of Obstetrics and Gynaecology, AUSL-IRCCS Reggio Emilia, 42123 Reggio Emilia, Italy;
| | - Andrea Palicelli
- Pathology Unit, AUSL-IRCCS Reggio Emilia, 42123 Reggio Emilia, Italy; (S.P.); (R.V.); (M.Z.); (A.P.)
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Bocsi GT, Kang J, Kennedy A, Singh L, Peditto S, Cardona DM. Developing Pathology Measures for the Quality Payment Program-Part I: A Quest for Meaningful Measures. Arch Pathol Lab Med 2020; 144:686-696. [PMID: 32459533 DOI: 10.5858/arpa.2019-0377-oa] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
CONTEXT.— Quality measures assess health care processes, outcomes, and patient perceptions associated with high-quality health care, which is commonly defined as care that is effective, safe, efficient, patient centered, equitable, and timely. Such measures are now being used in order to incentivize provision of high-quality health care. OBJECTIVE.— To meet the goals of the Quality Payment Program, quality measures will be developed from clinical practice guidelines and relevant, peer-reviewed research identifying evidence that the measure addresses 3 areas: a high-priority aspect of health care or a specific national health goal or priority; a meaningful focus, such as leading to a desired health outcome; and a gap or variation in care. DESIGN.— Within the College of American Pathologists (CAP), the Measures and Performance Assessment Subcommittee is tasked with developing useful performance measures. Participating practitioners can then select measures that are meaningful to their respective patients and practices, and reflect the quality of the services they provide. RESULTS.— The CAP developed 23 quality measures for reporting to the Centers for Medicare & Medicaid Services that reflect rigorous clinical evidence and address areas in need of performance improvement. CONCLUSIONS.— Because the implications of reporting on these pathology-specific metrics are significant, these measures and the process by which they were designed are presented here in peer-reviewed fashion. The measures described in this article (part 1) represent recent efforts by the CAP to develop meaningful measures that reflect rigorous clinical evidence and highlight areas with opportunities for performance improvement.
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Affiliation(s)
- Gregary T Bocsi
- From the Department of Pathology, University of Colorado-Anschutz Medical Campus, Aurora (Dr Bocsi); the Department of Pathology, NorthShore University Health System, Evanston, Illinois (Dr Kang); the Advocacy Division, College of American Pathologists, Washington, DC (Mss Kennedy, Singh, and Peditto); and the Department of Pathology, Duke University Medical Center, Durham, North Carolina (Dr Cardona). Ms Kennedy is currently with the American Society of Clinical Oncology, Arlington, Virginia
| | - Jason Kang
- From the Department of Pathology, University of Colorado-Anschutz Medical Campus, Aurora (Dr Bocsi); the Department of Pathology, NorthShore University Health System, Evanston, Illinois (Dr Kang); the Advocacy Division, College of American Pathologists, Washington, DC (Mss Kennedy, Singh, and Peditto); and the Department of Pathology, Duke University Medical Center, Durham, North Carolina (Dr Cardona). Ms Kennedy is currently with the American Society of Clinical Oncology, Arlington, Virginia
| | - Angela Kennedy
- From the Department of Pathology, University of Colorado-Anschutz Medical Campus, Aurora (Dr Bocsi); the Department of Pathology, NorthShore University Health System, Evanston, Illinois (Dr Kang); the Advocacy Division, College of American Pathologists, Washington, DC (Mss Kennedy, Singh, and Peditto); and the Department of Pathology, Duke University Medical Center, Durham, North Carolina (Dr Cardona). Ms Kennedy is currently with the American Society of Clinical Oncology, Arlington, Virginia
| | - Loveleen Singh
- From the Department of Pathology, University of Colorado-Anschutz Medical Campus, Aurora (Dr Bocsi); the Department of Pathology, NorthShore University Health System, Evanston, Illinois (Dr Kang); the Advocacy Division, College of American Pathologists, Washington, DC (Mss Kennedy, Singh, and Peditto); and the Department of Pathology, Duke University Medical Center, Durham, North Carolina (Dr Cardona). Ms Kennedy is currently with the American Society of Clinical Oncology, Arlington, Virginia
| | - Stephanie Peditto
- From the Department of Pathology, University of Colorado-Anschutz Medical Campus, Aurora (Dr Bocsi); the Department of Pathology, NorthShore University Health System, Evanston, Illinois (Dr Kang); the Advocacy Division, College of American Pathologists, Washington, DC (Mss Kennedy, Singh, and Peditto); and the Department of Pathology, Duke University Medical Center, Durham, North Carolina (Dr Cardona). Ms Kennedy is currently with the American Society of Clinical Oncology, Arlington, Virginia
| | - Diana M Cardona
- From the Department of Pathology, University of Colorado-Anschutz Medical Campus, Aurora (Dr Bocsi); the Department of Pathology, NorthShore University Health System, Evanston, Illinois (Dr Kang); the Advocacy Division, College of American Pathologists, Washington, DC (Mss Kennedy, Singh, and Peditto); and the Department of Pathology, Duke University Medical Center, Durham, North Carolina (Dr Cardona). Ms Kennedy is currently with the American Society of Clinical Oncology, Arlington, Virginia
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Hodgson A, Turashvili G. Pathology of Hereditary Breast and Ovarian Cancer. Front Oncol 2020; 10:531790. [PMID: 33117676 PMCID: PMC7550871 DOI: 10.3389/fonc.2020.531790] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Accepted: 09/01/2020] [Indexed: 12/11/2022] Open
Abstract
Hereditary breast and ovarian cancer (HBOC) syndrome is most commonly characterized by deleterious germline mutations in BRCA1 and BRCA2. HBOC patients are prone to the development of malignant neoplasms in multiple organs including the breast, ovary, and fallopian tube. From a pathological perspective, a number of morphological features have been described in BRCA-associated breast and tubo-ovarian cancers. For example, breast cancers diagnosed in BRCA1-mutation carriers are frequently of a high Nottingham grade and display medullary morphology and a triple-negative and/or a basal-like immunophenotype. In contrast, breast cancers in BRCA2-mutation carriers are similar to sporadic luminal-type tumors that are positive for hormone receptors and lack expression of human epidermal growth factor receptor 2. Cancers arising in the fallopian tube and ovary are almost exclusively of a high-grade serous histotype with frequent Solid, pseudo-Endometrioid, and Transitional cell carcinoma-like morphology (“SET features”), marked nuclear atypia, high mitotic index, abundant tumor infiltrating lymphocytes, and necrosis. In addition, pushing or infiltrative micropapillary patterns of invasion have been described in BRCA-associated metastases of tubo-ovarian high-grade serous carcinomas. Besides BRCA1 and BRCA2 mutations, alterations in a number of other homologous recombination genes with moderate penetrance, including PALB2, RAD51C, RAD51D, BRIP1, and others, have also been described in HBOC patients with varying frequency; however, distinct morphological characteristics of these tumors have not been well characterized to date. In this review, the above pathological features are discussed in detail and a focus is placed on how accurate pathologic interpretation plays an important role in allowing HBOC patients to receive the best possible management.
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Affiliation(s)
- Anjelica Hodgson
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
| | - Gulisa Turashvili
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.,Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, ON, Canada
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Malhotra H, Kowtal P, Mehra N, Pramank R, Sarin R, Rajkumar T, Gupta S, Bapna A, Bhattacharyya GS, Gupta S, Maheshwari A, Mannan AU, Reddy Kundur R, Sekhon R, Singhal M, Smruti B, SP S, Suryavanshi M, Verma A. Genetic Counseling, Testing, and Management of HBOC in India: An Expert Consensus Document from Indian Society of Medical and Pediatric Oncology. JCO Glob Oncol 2020; 6:991-1008. [PMID: 32628584 PMCID: PMC7392772 DOI: 10.1200/jgo.19.00381] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/21/2020] [Indexed: 01/08/2023] Open
Abstract
PURPOSE Hereditary breast and ovarian cancer (HBOC) syndrome is primarily characterized by mutations in the BRCA1/2 genes. There are several barriers to the implementation of genetic testing and counseling in India that may affect clinical decisions. These consensus recommendations were therefore convened as a collaborative effort to improve testing and management of HBOC in India. DESIGN Recommendations were developed by a multidisciplinary group of experts from the Indian Society of Medical and Pediatric Oncology and some invited experts on the basis of graded evidence from the literature and using a formal Delphi process to help reach consensus. PubMed and Google Scholar databases were searched to source relevant articles. RESULTS This consensus statement provides practical insight into identifying patients who should undergo genetic counseling and testing on the basis of assessments of family and ancestry and personal history of HBOC. It discusses the need and significance of genetic counselors and medical professionals who have the necessary expertise in genetic counseling and testing. Recommendations elucidate requirements of pretest counseling, including discussions on genetic variants of uncertain significance and risk reduction options. The group of experts recommended single-site mutation testing in families with a known mutation and next-generation sequencing coupled with multiplex ligation probe amplification for the detection of large genomic rearrangements for unknown mutations. Recommendations for surgical and lifestyle-related risk reduction approaches and management using poly (ADP-ribose) polymerase inhibitors are also detailed. CONCLUSION With rapid strides being made in the field of genetic testing/counseling in India, more oncologists are expected to include genetic testing/counseling as part of their clinical practice. These consensus recommendations are anticipated to help homogenize genetic testing and management of HBOC in India for improved patient care.
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Affiliation(s)
- Hemant Malhotra
- Department of Medical Oncology, Sri Ram Cancer Center, Mahatma Gandhi Medical College Hospital, Jaipur, India
| | - Pradnya Kowtal
- Sarin Laboratory and OIC Sanger Sequencing Facility, Advanced Centre for Treatment Research, and Education in Cancer, Navi Mumbai, India
| | - Nikita Mehra
- Department of Medical Oncology, Cancer Institute (WIA), Chennai, India
| | - Raja Pramank
- Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India
| | - Rajiv Sarin
- Radiation Oncology, Cancer Genetics Unit, Tata Memorial Centre and PI Sarin Laboratory, Advanced Centre for Treatment Research and Education in Cancer, Navi Mumbai, India
| | | | - Sudeep Gupta
- Tata Memorial Centre Advanced Centre for Treatment, Research, and Education in Cancer, Navi Mumbai, India
| | - Ajay Bapna
- Department of Medical Oncology, Bhagwan Mahavir Cancer Hospital Research Center, Jaipur, India
| | | | - Sabhyata Gupta
- Department of Gynae Oncology, Medanta-The Medicity, Gurgaon, India
| | - Amita Maheshwari
- Department of Gynecologic Oncology, Tata Memorial Centre, Mumbai, India
| | - Ashraf U. Mannan
- Clinical Diagnostics, Strand Center for Genomics and Personalized Medicine, Strand Life Sciences, Bangalore, India
| | | | - Rupinder Sekhon
- Gynae Oncology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
| | | | - B.K. Smruti
- Bombay Hospital and Medical Research Centre, Mumbai, India
| | - Somashekhar SP
- Manipal Comprehensive Cancer Center, Manipal Hospital, Bengaluru, India
| | - Moushumi Suryavanshi
- Molecular Diagnostics, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
| | - Amit Verma
- Molecular Oncology and Cancer Genetics, Max Hospital, New Delhi, India
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Santana dos Santos E, Lallemand F, Petitalot A, Caputo SM, Rouleau E. HRness in Breast and Ovarian Cancers. Int J Mol Sci 2020; 21:E3850. [PMID: 32481735 PMCID: PMC7312125 DOI: 10.3390/ijms21113850] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Revised: 04/25/2020] [Accepted: 04/28/2020] [Indexed: 02/06/2023] Open
Abstract
Ovarian and breast cancers are currently defined by the main pathways involved in the tumorigenesis. The majority are carcinomas, originating from epithelial cells that are in constant division and subjected to cyclical variations of the estrogen stimulus during the female hormonal cycle, therefore being vulnerable to DNA damage. A portion of breast and ovarian carcinomas arises in the context of DNA repair defects, in which genetic instability is the backdrop for cancer initiation and progression. For these tumors, DNA repair deficiency is now increasingly recognized as a target for therapeutics. In hereditary breast/ovarian cancers (HBOC), tumors with BRCA1/2 mutations present an impairment of DNA repair by homologous recombination (HR). For many years, BRCA1/2 mutations were only screened on germline DNA, but now they are also searched at the tumor level to personalize treatment. The reason of the inactivation of this pathway remains uncertain for most cases, even in the presence of a HR-deficient signature. Evidence indicates that identifying the mechanism of HR inactivation should improve both genetic counseling and therapeutic response, since they can be useful as new biomarkers of response.
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Affiliation(s)
- Elizabeth Santana dos Santos
- Department of Medical Biology and Pathology, Gustave Roussy, Cancer Genetics Laboratory, Gustave Roussy, 94800 Villejuif, France;
- Department of Clinical Oncology, A.C. Camargo Cancer Center, São Paulo 01509-010, Brazil
| | - François Lallemand
- Department of Genetics, Institut Curie, 75005 Paris, France; (F.L.); (A.P.); (S.M.C.)
- PSL Research University, 75005 Paris, France
| | - Ambre Petitalot
- Department of Genetics, Institut Curie, 75005 Paris, France; (F.L.); (A.P.); (S.M.C.)
- PSL Research University, 75005 Paris, France
| | - Sandrine M. Caputo
- Department of Genetics, Institut Curie, 75005 Paris, France; (F.L.); (A.P.); (S.M.C.)
- PSL Research University, 75005 Paris, France
| | - Etienne Rouleau
- Department of Medical Biology and Pathology, Gustave Roussy, Cancer Genetics Laboratory, Gustave Roussy, 94800 Villejuif, France;
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Factors associated with counseling and postoperative hormone therapy use in surgically menopausal women. ACTA ACUST UNITED AC 2020; 27:893-898. [PMID: 32404796 DOI: 10.1097/gme.0000000000001560] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE To determine the rates of and factors associated with preoperative counseling about menopausal symptoms and use of hormone therapy postoperatively in surgically menopausal women. METHODS This retrospective chart review included patients who underwent bilateral oophorectomies before age 52 at an academic institution during a 3-year period. We used descriptive analyses to characterize the sample and logistic regression to identify factors associated with preoperative counseling about and postoperative systemic hormone therapy for menopausal symptoms. RESULTS This review included 152 patients with a mean age of 44 ± 5 years (range 28-51). The indications for surgery were risk reduction (66%), BRCA positive (35%), and history of breast cancer (38%). One-third of women were not counseled preoperatively about menopausal symptoms. Women with cardiovascular disease and older age were less likely to receive preoperative counseling. Preoperative counseling was positively associated with risk reducing surgery.Out of 124 women with postoperative data regarding symptoms and treatment, 90 (73%) experienced vasomotor symptoms, 33 (27%) received hormone therapy (systemic or vaginal), 61 (49%) received other therapies, and 41 (33%) did not receive therapy. Younger age and negative history of breast cancer were significantly associated with systemic estrogen therapy use. CONCLUSIONS Within our cohort, 66% had no documentation of counseling about menopausal symptoms before surgical menopause. Most women experienced symptoms postoperatively, but less than one-third of symptomatic women received hormone therapy. We have an opportunity to improve anticipatory guidance and informed consent for women undergoing surgical menopause.
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Zhang X, Niu J, Che T, Zhu Y, Zhang H, Qu J. Fertility preservation in BRCA mutation carriers-efficacy and safety issues: a review. Reprod Biol Endocrinol 2020; 18:11. [PMID: 32070378 PMCID: PMC7027288 DOI: 10.1186/s12958-019-0561-0] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2019] [Accepted: 12/27/2019] [Indexed: 02/08/2023] Open
Abstract
BRCA mutation carriers face various situations that influence their fertility potential. There is still a lack of guideline or expert consensus on Fertility Preservation (FP) in BRCA mutation carriers and the necessity and safety of FP in BRCA mutation carriers is still in dispute. This review aims to focus on the population of BRCA mutation carriers by analyzing the existing FP strategies, comprehensively comparing the pros and cons of each strategy and its applicability.FP is a suggestion for BRCA mutation carriers with birth planning. Different FP strategies have different characteristics. Considering the particularity of BRCA mutation carriers, multiple factors need to be carefully considered. This review focuses on the applicability of each FP method for carriers under various circumstances. Available FP strategies including oocyte cryopreservation, ovarian tissue cryopreservation, preimplantation genetic diagnosis, and egg/embryo donation are analyzed by comparing existing methods comprehensively. In the attempt to provide an up-to-date decision-making guidance. Conditions taking into consideration were the carrier's age, the risk of breast and ovarian metastasis, plans for oncotherapy, FP outcome, time available for FP intervention and accessibility.Overall, FP is necessary and safe for BRCA mutation carriers. Among all available FP methods, oocyte cryopreservation is the most reliable procedure; ovarian tissue cryopreservation is the only way for preserving both fertility and endocrine function, recommended for pre-pubertal carriers and when time is limited for oocyte stimulation. A clear framework provides frontline clinical practitioners a new thought and eventually benefit thousands of BRCA mutation carriers.
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Affiliation(s)
- Xiaofu Zhang
- Department of Clinical Medicine, Medical College of Soochow University, Ren Ai Road 199, Suzhou Industrial Park, Suzhou, 215123, China
| | - Jingxin Niu
- Department of Clinical Medicine, Medical College of Soochow University, Ren Ai Road 199, Suzhou Industrial Park, Suzhou, 215123, China
| | - Tuanjie Che
- Laboratory of Precision Medicine and Translational Medicine, Suzhou Hospital Affiliated to Nanjing Medical University, Suzhou Science and Technology Town Hospital, Suzhou, 215153, China
| | - Yibei Zhu
- Department of Immunology, Medical College of Soochow University, Ren Ai Road 199, Suzhou Industrial Park, Suzhou, 215123, China
| | - Hongtao Zhang
- Department of Orthopedics, the First Affiliated Hospital of Soochow University, Soochow University, Suzhou, 215006, China
| | - Jing Qu
- Department of Cell Biology, Medical College of Soochow University, Ren Ai Road 199, Suzhou Industrial Park, Suzhou, 215123, China.
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Tumors of the Female Reproductive Organs. Fam Med 2020. [DOI: 10.1007/978-1-4939-0779-3_112-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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Stanisz M, Panczyk M, Kurzawa R, Grochans E. The Effect of Prophylactic Adnexectomy on the Quality of Life and Psychosocial Functioning of Women with the BRCA1/BRCA2 Mutations. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2019; 16:ijerph16244995. [PMID: 31818005 PMCID: PMC6950418 DOI: 10.3390/ijerph16244995] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/05/2019] [Revised: 12/04/2019] [Accepted: 12/05/2019] [Indexed: 12/21/2022]
Abstract
The main purpose of this study was to analyze the effect of risk-reducing salpingo-oophorectomy (RRSO) on the quality of life (QoL) and psychosocial functioning of patients with the BRCA1/BRCA2 mutations. This survey-based study was conducted using the Blatt-Kupperman Index, the Women’s Health Questionnaire, the Perceived Stress Scale, the State-Trait Anxiety Inventory, the Beck Depression Inventory-II, and the authors’ questionnaire. All calculations were done using Statistica 13.3. The QoL after RRSO was statistically significantly lower in most domains compared with the state before surgery. The greatest decline in the QoL was observed in the vasomotor symptoms domain (d = 0.953) and the smallest in the memory/concentration domain (d = 0.167). We observed a statistically significant decrease in the level of anxiety as a state (d = 0.381), as well as a statistically significant increase in the severity of climacteric symptoms (d = 0.315) and depressive symptoms (d = 0.125). Prophylactic surgeries of the reproductive organs have a negative effect on the QoL and psychosocial functioning of women with the BRCA1/2 mutations, as they increase the severity of depressive and climacteric symptoms. At the same time, these surgeries reduce anxiety as a state, which may be associated with the elimination of cancerophobia.
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Affiliation(s)
- Marta Stanisz
- Department of Gynecology and Reproductive Health, Pomeranian Medical University in Szczecin, 71-210 Szczecin, Poland; (M.S.); (R.K.)
| | - Mariusz Panczyk
- Department of Education and Research in Health Sciences, Medical University of Warsaw, 02-091 Warsaw, Poland;
| | - Rafał Kurzawa
- Department of Gynecology and Reproductive Health, Pomeranian Medical University in Szczecin, 71-210 Szczecin, Poland; (M.S.); (R.K.)
- Center of Gynecology and Treatmemt for Infertility “Vitrolive”, al. Wojska Polskiego 103, 70-483 Szczecin, Poland
| | - Elżbieta Grochans
- Department of Nursing, Pomeranian Medical University in Szczecin; ul. Żołnierska 48, 71-210 Szczecin, Poland
- Correspondence: ; Tel.: +48-91-4800-910
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Garcia C, Harrison K, Ring KL, Sullivan MW, Rauh LA, Modesitt SC. Genetic counseling referral for ovarian cancer patients: a call to action. Fam Cancer 2019; 18:303-309. [PMID: 30993488 DOI: 10.1007/s10689-019-00129-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
The hereditary contribution to ovarian cancer has been increasingly recognized over the past decade, with a 2014 Society of Gynecologic Oncology (SGO) recommendation for all women with epithelial ovarian cancer to be considered for genetic testing. The objective of the study was to determine if disparities exist in genetic referrals and characterize referral patterns over time. A retrospective cohort study included all women diagnosed with invasive epithelial ovarian cancer at the University of Virginia from 2004 to 2015. Clinicopathologic data were abstracted from the electronic medical record and analyzed for association with genetic referral and testing. We identified 696 cases, with a median age of 62 years and a median follow up of 25.2 months (range 1-115). Thirty-four percent were referred for genetic counseling with an 80% genetic testing rate in those women. Referrals increased from a rate of 8% in 2004 to 68% in 2015. On multivariable analysis, papillary serous histology (OR 1.6, 95% CI 1.0-2.6), stage III disease (OR 3.4, 95% CI 1.6-7.5), ovarian cancer family history (OR 2.6, 95% CI 1.5-4.6), breast cancer family history (OR 1.7, 95% CI 1.1-2.5), and diagnosis after 2014 (OR 2.3, 95% CI 1.3-4.1) remained significantly associated with genetics referral. Older age and living > 100 miles away were associated with decreased referral (OR 0.97, 95% CI 0.95-0.99 per year and OR 0.49, 95% CI 0.28-0.86). As only 68% of women with epithelial ovarian cancer were referred in 2015 innovative strategies such as Medicare coverage for counseling are still needed to universalize testing.
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Affiliation(s)
- Christine Garcia
- Thorton Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Virginia, Charlottesville, VA, USA
| | - Kara Harrison
- University of Virginia School of Medicine, Charlottesville, VA, USA
| | - Kari L Ring
- Thorton Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Virginia, Charlottesville, VA, USA
| | - Mackenzie W Sullivan
- University of Virginia School of Medicine, Charlottesville, VA, USA. .,Division of Gynecologic Oncology, University of Virginia Health System, University of Virginia School of Medicine, 1240 Lee Street, Box 800712, Charlottesville, VA, 22908-0712, USA.
| | - Lisa A Rauh
- Thorton Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Virginia, Charlottesville, VA, USA
| | - Susan C Modesitt
- Thorton Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Virginia, Charlottesville, VA, USA
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Jeffers L, Reid J, Fitzsimons D, Morrison PJ, Dempster M, Cochrane Gynaecological, Neuro‐oncology and Orphan Cancer Group. Interventions to improve psychosocial well-being in female BRCA-mutation carriers following risk-reducing surgery. Cochrane Database Syst Rev 2019; 10:CD012894. [PMID: 31595976 PMCID: PMC6784162 DOI: 10.1002/14651858.cd012894.pub2] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND Women who carry a pathogenic mutation in either a BRCA1 DNA repair associated or BRCA2 DNA repair associated (BRCA1 or BRCA2) gene have a high lifetime risk of developing breast and tubo-ovarian cancer. To manage this risk women may choose to undergo risk-reducing surgery to remove breast tissue, ovaries, and fallopian tubes. Surgery should increase survival, but can impact women's lives adversely at the psychological and psychosexual levels. Interventions to facilitate psychological adjustment and improve quality of life post risk-reducing surgery are needed. OBJECTIVES To examine psychosocial interventions in female BRCA carriers who have undergone risk-reducing surgery and to evaluate the effectiveness of such interventions on psychological adjustment and quality of life. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE and Embase via Ovid, CINAHL, PsycINFO, Web of Science up to April 2019 and Scopus up to January 2018. We also handsearched abstracts of scientific meetings and other relevant publications. SELECTION CRITERIA We included randomised controlled trials (RCT), non-randomised studies (NRS), prospective and retrospective cohort studies and interventional studies using baseline and postintervention analyses in female BRCA carriers who have undergone risk-reducing surgery. DATA COLLECTION AND ANALYSIS Two review authors independently assessed eligibility studies for inclusion in the review. We used standard methodological procedures expected by Cochrane. MAIN RESULTS We screened 4956 records from the searches, selecting 34 unique studies for full-text scrutiny, of which two met the inclusion criteria: one RCT and one NRS. The included studies assessed 113 female BRCA carriers who had risk-reducing surgery, but there was attrition, and outcome data were not available for all participants at final study assessments. We assessed the RCT as at a high risk of bias whilst the NRS did not have a control group. Our GRADE assessment of the studies was very low-certainty due to the paucity of data and methodological shortcomings of the studies. The primary outcome of quality of life was only measured in the RCT and that was specific to the menopause. Both studies reported on psychological distress and sexual function. Neither study measured body image, perhaps because this is most often associated with risk-reducing mastectomy rather than oophorectomy.The RCT (66 participants recruited with 48 followed to 12 months) assessed the short- and long-term effects of an eight-week mindfulness-based stress reduction (MBSR) training programme on quality of life, sexual functioning, and sexual distress in female BRCA carriers (n = 34) in a specialised family cancer clinic in the Netherlands compared to female BRCA carriers (n = 32) who received usual care. Measurements on the Menopause-Specific Quality of Life Questionnaire (MENQOL) showed some improvement at 3 and 12 months compared to the usual care group. At 3 months the mean MENQOL scores were 3.5 (95% confidence interval (CI) 3.0 to 3.9) and 3.8 (95% CI 3.3 to 4.2) for the MBSR and usual care groups respectively, whilst at 12 months the corresponding values were 3.6 (95% CI 3.1 to 4.0) and 3.9 (95% CI 3.5 to 4.4) (1 study; 48 participants followed up at 12 months). However, these results should be interpreted with caution due to the very low-certainty of the evidence, where a lower score is better. Other outcome measures on the Female Sexual Function Index and the Female Sexual Distress Scale showed no significant differences between the two groups. Our GRADE assessment of the evidence was very low-certainty due to the lack of blinding of participants and personnel, attrition bias and self-selection (as only one-third of eligible women chose to participate in the study) and serious imprecision due to the small sample size and wide 95% CI.The NRS comprised 37 female BRCA carriers selected from three Boston-area hospitals who had undergone a novel sexual health intervention following risk-reducing salpingo-oophorectomy (RRSO) without a history of tubo-ovarian cancer. The intervention consisted of targeted sexual-health education, body awareness and relaxation training, and mindfulness-based cognitive therapy strategies, followed by two sessions of tailored telephone counselling. This was a single-arm study without a control group. Our GRADE assessment of the evidence was very low-certainty, and as there was no comparison group in the included study, we could not estimate a relative effect. The study reported change in psychosexual adjustment from baseline to postintervention (median 2.3 months) using measures of Female Sexual Function Index (n = 34), which yielded change with a mean of 3.91, standard deviation (SD) 9.12, P = 0.018 (1 study, 34 participants; very low-certainty evidence). The Brief Symptom Inventory, Global Severity Index yielded a mean change of 3.92, SD 5.94, P < 0.001. The Sexual Self-Efficacy Scale yielded change with a mean of 12.14, SD 20.56, P < 0.001. The Sexual Knowledge Scale reported mean change of 1.08, SD 1.50, P < 0.001 (n = 36). Participant satisfaction was measured by questionnaire, and 100% participants reported that they enjoyed taking part in the psychoeducation group and felt "certain" or "very certain" that they had learned new skills to help them cope with the sexual side effects of RRSO. AUTHORS' CONCLUSIONS The effect of psychosocial interventions on quality of life and emotional well-being in female BRCA carriers who undergo risk-reducing surgery is uncertain given the very low methodological quality in the two studies included in the review. The absence of such interventions highlights the need for partnership between researchers and clinicians in this specific area to take forward the patient-reported outcomes and develop interventions to address the psychosocial issues related to risk-reducing surgery in female BRCA carriers, particularly in this new era of genomics, where testing may become more mainstream and many more women are identified as gene carriers.
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Affiliation(s)
- Lisa Jeffers
- Regional Medical Genetics CentreMedical GeneticsBelfast Health and Social Care TrustLisburn RoadBelfastUKBT9 7AB
| | - Joanne Reid
- Queen's University BelfastSchool of Nursing and Midwifery10 Malone RoadBelfastUKBT9 5BN
| | - Donna Fitzsimons
- Queen's University BelfastSchool of Nursing and Midwifery10 Malone RoadBelfastUKBT9 5BN
| | - Patrick J Morrison
- Regional Medical Genetics CentreMedical GeneticsBelfast Health and Social Care TrustLisburn RoadBelfastUKBT9 7AB
- Queen's University BelfastCentre for Cancer Research and Cell Biology97 Lisburn RoadBelfastUKBT9 7AE
| | - Martin Dempster
- Queen's University BelfastSchool of PsychologyUniversity RoadBelfastNorthern IrelandUKBT7 1NN
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Chern JY, Lee SS, Frey MK, Lee J, Blank SV. The influence of BRCA variants of unknown significance on cancer risk management decision-making. J Gynecol Oncol 2019; 30:e60. [PMID: 31074248 PMCID: PMC6543104 DOI: 10.3802/jgo.2019.30.e60] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2018] [Revised: 01/07/2019] [Accepted: 01/29/2019] [Indexed: 11/30/2022] Open
Abstract
OBJECTIVE To compare gynecological cancer risk management between women with BRCA variants of unknown significance (VUS) to women with negative genetic testing. METHODS Ninety-nine patients whose BRCA genetic testing yielded VUS were matched with 99 control patients with definitive negative BRCA results at a single institution. Demographics and risk management decisions were obtained through chart review. Primary outcome was the rate of risk-reducing bilateral salpingo-oophorectomy (RRBSO). Chi square tests, t-tests, and logistic regression were performed, with significance of p<0.05. RESULTS VUS patients were more likely to be non-Caucasian (p=0.000) and of Ashkenazi-Jewish descent (p=0.000). There was no difference in gynecologic oncology referrals or recommendations to screen or undergo risk-reducing surgery for VUS vs. negative patients. Ultimately, 44 patients (22%) underwent RRBSO, with no significant difference in surgical rate based on the presence of VUS. Ashkenazi-Jewish descent was associated with a 4.5 times increased risk of RRBSO (OR=4.489; 95% CI=1.484-13.579) and family history of ovarian cancer was associated with a 2.6 times risk of RRBSO (OR=2.641; 95% CI=1.107-6.299). CONCLUSION In our institution, patients with VUS were surgically managed similarly to those with negative BRCA testing. The numbers of patients with VUS are likely to increase with the implementation of multi-gene panel testing. Our findings underscore the importance of genetic counseling and individualized screening and prevention strategies in the management of genetic testing results.
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Affiliation(s)
- Jing Yi Chern
- Department of Gynecologic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Sarah S Lee
- Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, New York University School of Medicine, New York, NY, USA.
| | - Melissa K Frey
- Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, Weill Cornell Medicine, New York, NY, USA
| | - Jessica Lee
- Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, New York University School of Medicine, New York, NY, USA
| | - Stephanie V Blank
- Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Toss A, Molinaro E, Sammarini M, Del Savio MC, Cortesi L, Facchinetti F, Grandi G. Hereditary ovarian cancers: state of the art. Minerva Med 2019; 110:301-319. [DOI: 10.23736/s0026-4806.19.06091-9] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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Kurian AW, Ward KC, Howlader N, Deapen D, Hamilton AS, Mariotto A, Miller D, Penberthy LS, Katz SJ. Genetic Testing and Results in a Population-Based Cohort of Breast Cancer Patients and Ovarian Cancer Patients. J Clin Oncol 2019; 37:1305-1315. [PMID: 30964716 PMCID: PMC6524988 DOI: 10.1200/jco.18.01854] [Citation(s) in RCA: 275] [Impact Index Per Article: 45.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/16/2019] [Indexed: 01/18/2023] Open
Abstract
PURPOSE Genetic testing for cancer risk has expanded rapidly. We examined clinical genetic testing and results among population-based patients with breast and ovarian cancer. METHODS The study included all women 20 years of age or older diagnosed with breast or ovarian cancer in California and Georgia between 2013 and 2014 and reported to the SEER registries covering the entire state populations. SEER data were linked to results from four laboratories that performed nearly all germline cancer genetic testing. Testing use and results were analyzed at the gene level. RESULTS There were 77,085 patients with breast cancer and 6,001 with ovarian cancer. Nearly one quarter of those with breast cancer (24.1%) and one third of those with ovarian cancer (30.9%) had genetic test results. Among patients with ovarian cancer, testing was lower in blacks (21.6%; 95% CI, 18.1% to 25.4%; v whites, 33.8%; 95% CI, 32.3% to 35.3%) and uninsured patients (20.8%; 95% CI, 15.5% to 26.9%; v insured patients, 35.3%; 95% CI, 33.8% to 36.9%). Prevalent pathogenic variants in patients with breast cancer were BRCA1 (3.2%), BRCA2 (3.1%), CHEK 2 (1.6%), PALB2 (1.0%), ATM (0.7%), and NBN (0.4%); in patients with ovarian cancer, prevalent pathogenic variants were BRCA1 (8.7%), BRCA2 (5.8%), CHEK2 (1.4%), BRIP1 (0.9%), MSH2 (0.8%), and ATM (0.6%). Racial/ethnic differences in pathogenic variants included BRCA1 (ovarian cancer: whites, 7.2%; 95% CI, 5.9% to 8.8%; v Hispanics, 16.1%; 95% CI, 11.8% to 21.2%) and CHEK2 (breast cancer: whites, 2.3%; 95% CI, 1.8% to 2.8%; v blacks, 0.1%; 95% CI, 0% to 0.8%). When tested for all genes that current guidelines designate as associated with their cancer type, 7.8% of patients with breast cancer and 14.5% of patients with ovarian cancer had pathogenic variants. CONCLUSION Clinically-tested patients with breast and ovarian cancer in two large, diverse states had 8% to 15% prevalence of actionable pathogenic variants. Substantial testing gaps and disparities among patients with ovarian cancer are targets for improvement.
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Allen C, Escoffery C, Haardörfer R, McBride C. Factors Influencing Not Perceiving Family Health History Assessments as Important: Opportunities to Improve Dissemination of Evidence-Based Population Screening for Cancer. Public Health Genomics 2019; 21:144-153. [DOI: 10.1159/000499125] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2018] [Accepted: 02/25/2019] [Indexed: 11/19/2022] Open
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Assessment of High Risk of Hereditary Breast and Ovarian Cancer (HBOC) and Acceptance for Genetic Testing Among Cases of Ovarian and Breast Cancer in Indian Set-up. INDIAN JOURNAL OF GYNECOLOGIC ONCOLOGY 2019. [DOI: 10.1007/s40944-019-0280-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
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Vermeulen RFM, Korse CM, Kenter GG, Brood-van Zanten MMA, Beurden MV. Safety of hormone replacement therapy following risk-reducing salpingo-oophorectomy: systematic review of literature and guidelines. Climacteric 2019; 22:352-360. [PMID: 30905183 DOI: 10.1080/13697137.2019.1582622] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
Background: Women at high risk to develop ovarian cancer opt for risk-reducing salpingo-oophorectomy (RRSO) to reduce the risk by 80-96%. RRSO leads to a direct onset of menopause in premenopausal women. Hormone replacement therapy (HRT) can be used to mitigate menopausal symptoms after RRSO. However, it is unclear whether HRT in these women is safe in terms of breast cancer (BC) risk. Methods: We performed a literature search and investigated national guidelines on the use of HRT following RRSO in BRCA1 and BRCA2 mutation carriers. We analyzed differences and similarities between the guidelines and describe what these guidelines were based upon. Results: Seven articles regarding HRT following RRSO in BRCA1 and BRCA2 mutation carriers were identified. None of the included studies yielded any evidence that short-term use of HRT following RRSO increases the risk of developing BC or negates the protective effect of RRSO in BRCA1/2 mutation carriers without a personal history of BC. Eleven national guidelines were found and described. Conclusion: Short-term use of HRT after RRSO seems to be safe. The literature is more favorable toward estrogen alone. The ideal dosage and duration of use are unknown and remain to be investigated in future studies.
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Affiliation(s)
- R F M Vermeulen
- a Department of Gynecology , The Netherlands Cancer Institute , Amsterdam , the Netherlands
| | - C M Korse
- b Department of Laboratory Medicine , The Netherlands Cancer Institute , Amsterdam , the Netherlands
| | - G G Kenter
- a Department of Gynecology , The Netherlands Cancer Institute , Amsterdam , the Netherlands
| | - M M A Brood-van Zanten
- a Department of Gynecology , The Netherlands Cancer Institute , Amsterdam , the Netherlands.,c Amsterdam UMC , Amsterdam , the Netherlands
| | - M van Beurden
- a Department of Gynecology , The Netherlands Cancer Institute , Amsterdam , the Netherlands
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Staples JN, Duska LR. Cancer Screening and Prevention Highlights in Gynecologic Cancer. Obstet Gynecol Clin North Am 2019; 46:19-36. [DOI: 10.1016/j.ogc.2018.09.002] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Silver MI, Klein W, Samimi G, Minasian L, Loud J, Roberts MC. Concordance with BRCA1/2 testing guidelines among women in The Health of Women (HOW) Study ®. Breast Cancer Res Treat 2019; 173:719-726. [PMID: 30413980 DOI: 10.1007/s10549-018-5035-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2018] [Accepted: 10/29/2018] [Indexed: 01/26/2023]
Abstract
PURPOSE To evaluate factors associated with compliance to the National Comprehensive Cancer Network (NCCN) guidelines for BRCA1/2 testing and identify groups who are at risk of under- and over-use of BRCA1/2 testing. METHODS Data included 20,758 women from Dr. Susan Love Research Foundation's The Health of Women (HOW) Study®. Multinomial logistic regression was used to examine the association of socioeconomic and demographic characteristics with whether the woman was over-, under-, or appropriately tested for BRCA1/2 mutations, per 2015 NCCN guidelines. RESULTS 3894 women (18.8%) reported BRCA1/2 testing. 5628 (27.1%) women who met NCCN criteria for testing were not tested. Among women with a history of breast cancer, those without health insurance were more likely to be under-tested (OR 2.04, 95% CI 1.15-3.60) than those with managed care insurance, and higher education was associated with a lower likelihood of under-testing (Graduate/professional degree OR 0.71, 95% CI 0.55-0.91). CONCLUSION Almost 30% of women were under-tested, indicating that many high-risk women who may benefit from genetic testing are currently being missed. Without appropriate testing, providers are unable to tailor screening recommendations to those carrying mutations who are at highest risk. Patient and healthcare provider education and outreach targeted to low-income and under-served populations may assist in reducing under-testing.
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Affiliation(s)
- Michelle I Silver
- Division of Cancer Control and Population Sciences, National Cancer Institute, 9609 Medical Center Drive, Rockville, MD, 20850, USA.
- Division of Cancer Epidemiology & Genetics, National Cancer Institute, Rockville, MD, USA.
| | - William Klein
- Division of Cancer Control and Population Sciences, National Cancer Institute, 9609 Medical Center Drive, Rockville, MD, 20850, USA
| | - Goli Samimi
- Division of Cancer Prevention, National Cancer Institute, Rockville, MD, USA
| | - Lori Minasian
- Division of Cancer Prevention, National Cancer Institute, Rockville, MD, USA
| | - Jennifer Loud
- Division of Cancer Epidemiology & Genetics, National Cancer Institute, Rockville, MD, USA
| | - Megan C Roberts
- Division of Cancer Control and Population Sciences, National Cancer Institute, 9609 Medical Center Drive, Rockville, MD, 20850, USA
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Mallen AR, Townsend MK, Tworoger SS. Risk Factors for Ovarian Carcinoma. Hematol Oncol Clin North Am 2018; 32:891-902. [DOI: 10.1016/j.hoc.2018.07.002] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
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Nair N, Schwartz M, Guzzardi L, Durlester N, Pan S, Overbey J, Chuang L. Hysterectomy at the time of risk-reducing surgery in BRCA carriers. Gynecol Oncol Rep 2018; 26:71-74. [PMID: 30364812 PMCID: PMC6198097 DOI: 10.1016/j.gore.2018.10.003] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2018] [Revised: 10/02/2018] [Accepted: 10/03/2018] [Indexed: 11/02/2022] Open
Abstract
In this study, women at risk for BRCA were surveyed to understand their choice of prophylactic surgery and associated risk of uterine cancers. The study was conducted as an anonymous online web-based survey that assessed personal and family histories and choice of prophylactic surgery. Respondents were targeted through social media groups that bring awareness to hereditary breast and ovarian cancer. The study cohort included an international group of 601 respondents. The majority were female (99.3%), in their 40s (34.2%), and had completed college or graduate school (68.8%). 87% of respondents carry BRCA gene mutation. Of 339 respondents who underwent risk-reducing salpingo-oophorectomy (RRSO), 55.8% had a hysterectomy at time of RRSO. Most common reasons for hysterectomy at time of RRSO included: 39% provider recommendation, 27.6% personal desire, 9.7% benign indications, 1.6% cancer in uterus, 1.1% precancerous uterine lesion, and 21.1% other (N = 185). In this cohort, nine were diagnosed with uterine cancer. Three were diagnosed after risk-reducing surgery. Both patients with uterine serous carcinoma were BRCA1 carriers. Two thirds of BRCA carriers surveyed had undergone RRSO. Of these, more than half had hysterectomy at time of RRSO. One third chose to have hysterectomy based on surgeon recommendation. <1% (2 out of 258) of BRCA1 gene mutation carriers reported being diagnosed with uterine serous carcinomas. While this incidence is low, it may be an underestimate based on the limitations of this study. Additional studies are needed to select which patients will benefit from concurrent hysterectomy and RRSO.
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Affiliation(s)
- Navya Nair
- Department of Obstetrics, Gynecology, and Reproductive Services, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Melissa Schwartz
- Department of Obstetrics, Gynecology, and Reproductive Services, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Lisa Guzzardi
- BRCA Advanced 101 & 102 Journal Club, New York, NY, USA
| | | | - Stephanie Pan
- Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Jessica Overbey
- Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Giannos A, Stavrou S, Douskos A, Drakakis P, Loutradis D. A salpingeal carcinoma revealed after prophylactic salpingoophorectomy in an asymptomatic BRCA1 carrier with breast malignancy. Int J Surg Case Rep 2018; 52:107-110. [PMID: 30340058 PMCID: PMC6197605 DOI: 10.1016/j.ijscr.2018.10.014] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2018] [Revised: 09/26/2018] [Accepted: 10/05/2018] [Indexed: 11/10/2022] Open
Abstract
The median age between BRCA results receipt and RRSO should be reconsidered. Occasionally, no correlation exists between tumor size, malignancy or metastasis. Initial total excision of the mass, ensure the positive histological diagnosis. Introduction BRCA1 inherited mutation carriers face a lifetime risk of 72% to develop breast cancer and a percentage of 44% risk for ovarian cancer. Presentation of case We present a case of a 35-year old Caucasian woman who, after the excision of a possible malignant finding on the right breast, was diagnosed with ductal breast carcinoma. The patient treatment included first chemotherapy and radiotherapy and then prophylactic bilateral mastectomy with plastic reconstructive surgery. At the age of 37, she underwent prophylactic laparoscopic bilateral salpingoophorectomy. The histological diagnosis of the surgical specimens was suggestive of a unilateral invasive high grade salpingeal cancer and the patient underwent an abdominal hysterectomy by laparotomy, omentectomy and bilateral pelvic lymphadenectomy. Discussion Women with known BRCA mutations are strongly recommended to consider a risk reducing prophylactic salpingoophorectomy (RRSO) from their early 40 s to gain maximum benefit in cancer risk reduction from the procedure. The prevalence of occult carcinomas in BRCA1 carriers is almost 1, 5% if the prophylactic bilateral salpingoophorectomy is performed before the age of 40, while this percentage may be increased to 3, 8% for women who undergo the surgery between 40 and 49 years. Conclusion We present an interesting case, of an accidentally revealed salpingeal carcinoma via RRSO in an asymptomatic young premenopausal woman.
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Affiliation(s)
- Aris Giannos
- 1(st)OB.GYN Department, School of Medicine, National and Kapodistrian University of Athens, Alexandra Hospital, Lourou and Vasilissis Sofias Ave, 11528 Athens, Greece.
| | - Sofoklis Stavrou
- 1(st)OB.GYN Department, School of Medicine, National and Kapodistrian University of Athens, Alexandra Hospital, Lourou and Vasilissis Sofias Ave, 11528 Athens, Greece.
| | - Athanasios Douskos
- 1(st)OB.GYN Department, School of Medicine, National and Kapodistrian University of Athens, Alexandra Hospital, Lourou and Vasilissis Sofias Ave, 11528 Athens, Greece.
| | - Peter Drakakis
- 1(st)OB.GYN Department, School of Medicine, National and Kapodistrian University of Athens, Alexandra Hospital, Lourou and Vasilissis Sofias Ave, 11528 Athens, Greece.
| | - Dimitrios Loutradis
- 1(st)OB.GYN Department, School of Medicine, National and Kapodistrian University of Athens, Alexandra Hospital, Lourou and Vasilissis Sofias Ave, 11528 Athens, Greece.
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Doren A, Vecchiola A, Aguirre B, Villaseca P. Gynecological–endocrinological aspects in women carriers of BRCA1/2 gene mutations. Climacteric 2018; 21:529-535. [DOI: 10.1080/13697137.2018.1514006] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Affiliation(s)
- A. Doren
- Obstetrics and Gynecology Department, Faculty of Medicine, Universidad Católica del Maule, Talca, Chile
| | - A. Vecchiola
- Endocrinology Department, Faculty of Medicine, Millenium Institute of Immunology and Immunotherapy, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - B. Aguirre
- Breast Imaging, Radiology Service, Clínica Las Condes, Santiago, Chile
| | - P. Villaseca
- Endocrinology Department, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
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Dossa F, Cusimano MC, Sutradhar R, Metcalfe K, Little T, Lerner-Ellis J, Eisen A, Meschino WS, Baxter NN. Real-world health services utilisation and outcomes after BRCA1 and BRCA2 testing in Ontario, Canada: the What Comes Next Cohort Study protocol. BMJ Open 2018; 8:e025317. [PMID: 30181190 PMCID: PMC6129086 DOI: 10.1136/bmjopen-2018-025317] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
INTRODUCTION Women who have pathogenic mutations in the BRCA1 and BRCA2 genes are at greatly increased risks for breast and ovarian cancers. Although risk-reduction strategies can be undertaken by these women, knowledge regarding the uptake of these strategies is limited. Additionally, the healthcare behaviours of women who receive inconclusive test results are not known. This study protocol describes the creation of a retrospective cohort of women who have undergone genetic testing for BRCA1 and BRCA2, linking genetic test results with administrative data to quantify the uptake of risk-reduction strategies and to assess long-term cancer and non-cancer outcomes after genetic testing. METHODS AND ANALYSIS Approximately two-thirds of BRCA1 and BRCA2 testing in Ontario, Canada is performed at North York General Hospital (NYGH) and Mount Sinai Hospital (MSH), Toronto. We will use registries at these sites to assemble a cohort of approximately 17 000 adult women who underwent BRCA1 and BRCA2 testing from January 2007 to April 2016. Trained chart abstractors will obtain detailed information for all women tested over this period, including demographics, personal and family cancer histories and genetic test results. We will link these data to provincial administrative databases, enabling assessment of healthcare utilisation and long-term outcomes after testing. Study outcomes will include the uptake of breast cancer screening and prophylactic breast and ovarian surgery, cancer incidence and mortality and incidence of non-cancer health outcomes, including cardiovascular, osteoporotic and neurodegenerative disease. ETHICS AND DISSEMINATION This study has been approved by the Research Ethics Boards at NYGH (no 16-0035), MSH (no 13-0124) and Sunnybrook Health Sciences Centre (no 275-2016). We plan to disseminate research findings through peer-reviewed publications and presentations at national and international meetings.
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Affiliation(s)
- Fahima Dossa
- Division of General Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada
- Department of Surgery, St Michael's Hospital, Toronto, Ontario, Canada
- Institute for Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada
| | - Maria C Cusimano
- Institute for Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada
- Department of Obstetrics and Gynaecology, University of Toronto, Toronto, Ontario, Canada
| | - Rinku Sutradhar
- Institute for Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada
- Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada
| | - Kelly Metcalfe
- Lawrence S Bloomberg Faculty of Nursing, University of Toronto, Toronto, Ontario, Canada
| | - Tari Little
- Department of Surgery, St Michael's Hospital, Toronto, Ontario, Canada
| | - Jordan Lerner-Ellis
- Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
- Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada
| | - Andrea Eisen
- Sunnybrook Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
| | - Wendy S Meschino
- Department of Molecular Genetics, North York General Hospital, Toronto, Ontario, Canada
- Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada
| | - Nancy N Baxter
- Division of General Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada
- Department of Surgery, St Michael's Hospital, Toronto, Ontario, Canada
- Institute for Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada
- Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada
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Kim M, Kim YH, Kim YB, Kim J, Kim JW, Park MH, Park JH, Rhee JH, Lim MC, Hong JS. Bilateral salpingectomy to reduce the risk of ovarian/fallopian/peritoneal cancer in women at average risk: a position statement of the Korean Society of Obstetrics and Gynecology (KSOG). Obstet Gynecol Sci 2018; 61:542-552. [PMID: 30254990 PMCID: PMC6137013 DOI: 10.5468/ogs.2018.61.5.542] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2018] [Revised: 09/04/2018] [Accepted: 09/04/2018] [Indexed: 11/09/2022] Open
Abstract
Based on the current understanding of a preventive effect of bilateral salpingectomy on ovarian/fallopian/peritoneal cancers, the Korean Society of Obstetrics and Gynecology, Korean Society of Gynecologic Endocrinology, Korean Society of Gynecologic Oncology, Korean Society of Maternal Fetal Medicine, and Korean Society for Reproductive Medicine support the following recommendations: • Women scheduled for hysterectomy for benign gynecologic disease should be informed that bilateral salpingectomy reduces the risk of ovarian/fallopian/peritoneal cancer, and they should be counseled regarding this procedure at the time of hysterectomy. • Although salpingectomy is generally considered as a safe procedure in terms of preserving ovarian reserve, there is a lack of evidences representing its long-term outcomes. Therefore, patients should be informed about the minimal potential of this procedure for decreasing ovarian reserve. • Prophylactic salpingectomy during vaginal hysterectomy is favorable in terms of prevention of ovarian/fallopian/peritoneal cancer, although operation-related complications minimally increase with this procedure, compared to the complications associated with vaginal hysterectomy alone. Conversion to open or laparoscopic approach from vaginal approach to perform prophylactic salpingectomy is not recommended. • Women who desire permanent sterilization at the time of cesarean delivery could be counseled for prophylactic salpingectomy before surgery on an individual basis.
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Affiliation(s)
- Miseon Kim
- Department of Obstetrics and Gynecology, CHA Gangnam Medical Center, CHA University School of Medicine, Seoul, Korea
| | - Young-Han Kim
- Department of Obstetrics and Gynecology, Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Korea
| | - Yong Beom Kim
- Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Jayeon Kim
- Department of Obstetrics and Gynecology, CHA Seoul Fertility Center, CHA University School of Medicine, Seoul, Korea
| | - Jae-Weon Kim
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
| | - Mi Hye Park
- Department of Obstetrics and Gynecology, Ewha Womans University College of Medicine, Seoul, Korea
| | - Joo Hyun Park
- Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Jeong Ho Rhee
- Department of Obstetrics and Gynecology, Keimyung University School of Medicine, Daegu, Korea
| | - Myong Cheol Lim
- Cancer Healthcare Research Branch and Center for Uterine Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea
| | - Joon-Seok Hong
- Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Seongnam, Korea
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Eleje GU, Eke AC, Ezebialu IU, Ikechebelu JI, Ugwu EO, Okonkwo OO. Risk-reducing bilateral salpingo-oophorectomy in women with BRCA1 or BRCA2 mutations. Cochrane Database Syst Rev 2018; 8:CD012464. [PMID: 30141832 PMCID: PMC6513554 DOI: 10.1002/14651858.cd012464.pub2] [Citation(s) in RCA: 60] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND The presence of deleterious mutations in breast cancer 1 gene (BRCA1) or breast cancer 2 gene (BRCA2) significantly increases the risk of developing some cancers, such as breast and high-grade serous cancer (HGSC) of ovarian, tubal and peritoneal origin. Risk-reducing salpingo-oophorectomy (RRSO) is usually recommended to BRCA1 or BRCA2 carriers after completion of childbearing. Despite prior systematic reviews and meta-analyses on the role of RRSO in reducing the mortality and incidence of breast, HGSC and other cancers, RRSO is still an area of debate and it is unclear whether RRSO differs in effectiveness by type of mutation carried. OBJECTIVES To assess the benefits and harms of RRSO in women with BRCA1 or BRCA2 mutations. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 7) in The Cochrane Library, MEDLINE Ovid, Embase Ovid and trial registries, with no language restrictions up to July 2017. We handsearched abstracts of scientific meetings and other relevant publications. SELECTION CRITERIA We included non-randomised trials (NRS), prospective and retrospective cohort studies, and case series that used statistical adjustment for baseline case mix using multivariable analyses comparing RRSO versus no RRSO in women without a previous or coexisting breast, ovarian or fallopian tube malignancy, in women with or without hysterectomy, and in women with a risk-reducing mastectomy (RRM) before, with or after RRSO. DATA COLLECTION AND ANALYSIS We extracted data and performed meta-analyses of hazard ratios (HR) for time-to-event variables and risk ratios (RR) for dichotomous outcomes, with 95% confidence intervals (CI). To assess bias in the studies, we used the ROBINS-I 'Risk of bias' assessment tool. We quantified inconsistency between studies by estimating the I2 statistic. We used random-effects models to calculate pooled effect estimates. MAIN RESULTS We included 10 cohort studies, comprising 8087 participants (2936 (36%) surgical participants and 5151 (64%) control participants who were BRCA1 or BRCA2 mutation carriers. All the studies compared RRSO with or without RRM versus no RRSO (surveillance). The certainty of evidence by GRADE assessment was very low due to serious risk of bias. Nine studies, including 7927 women, were included in the meta-analyses. The median follow-up period ranged from 0.5 to 27.4 years. MAIN OUTCOMES overall survival was longer with RRSO compared with no RRSO (HR 0.32, 95% CI 0.19 to 0.54; P < 0.001; 3 studies, 2548 women; very low-certainty evidence). HGSC cancer mortality (HR 0.06, 95% CI 0.02 to 0.17; I² = 69%; P < 0.0001; 3 studies, 2534 women; very low-certainty evidence) and breast cancer mortality (HR 0.58, 95% CI 0.39 to 0.88; I² = 65%; P = 0.009; 7 studies, 7198 women; very low-certainty evidence) were lower with RRSO compared with no RRSO. None of the studies reported bone fracture incidence. There was a difference in favour of RRSO compared with no RRSO in terms of ovarian cancer risk perception quality of life (MD 15.40, 95% CI 8.76 to 22.04; P < 0.00001; 1 study; very low-certainty evidence). None of the studies reported adverse events.Subgroup analyses for main outcomes: meta-analysis showed an increase in overall survival among women who had RRSO versus women without RRSO who were BRCA1 mutation carriers (HR 0.30, 95% CI 0.17 to 0.52; P < 0001; I² = 23%; 3 studies; very low-certainty evidence) and BRCA2 mutation carriers (HR 0.44, 95% CI 0.23 to 0.85; P = 0.01; I² = 0%; 2 studies; very low-certainty evidence). The meta-analysis showed a decrease in HGSC cancer mortality among women with RRSO versus no RRSO who were BRCA1 mutation carriers (HR 0.10, 95% CI 0.02 to 0.41; I² = 54%; P = 0.001; 2 studies; very low-certainty evidence), but uncertain for BRCA2 mutation carriers due to low frequency of HGSC cancer deaths in BRCA2 mutation carriers. There was a decrease in breast cancer mortality among women with RRSO versus no RRSO who were BRCA1 mutation carriers (HR 0.45, 95% CI 0.30 to 0.67; I² = 0%; P < 0.0001; 4 studies; very low-certainty evidence), but not for BRCA2 mutation carriers (HR 0.88, 95% CI 0.42 to 1.87; I² = 63%; P = 0.75; 3 studies; very low-certainty evidence). One study showed a difference in favour of RRSO versus no RRSO in improving quality of life for ovarian cancer risk perception in women who were BRCA1 mutation carriers (MD 10.70, 95% CI 2.45 to 18.95; P = 0.01; 98 women; very low-certainty evidence) and BRCA2 mutation carriers (MD 13.00, 95% CI 3.59 to 22.41; P = 0.007; very low-certainty evidence). Data from one study showed a difference in favour of RRSO and RRM versus no RRSO in increasing overall survival (HR 0.14, 95% CI 0.02 to 0.98; P = 0.0001; I² = 0%; low-certainty evidence), but no difference for breast cancer mortality (HR 0.78, 95% CI 0.51 to 1.19; P = 0.25; very low-certainty evidence). The risk estimates for breast cancer mortality according to age at RRSO (50 years of age or less versus more than 50 years) was not protective and did not differ for BRCA1 (HR 0.85, 95% CI 0.64 to 1.11; I² = 16%; P = 0.23; very low-certainty evidence) and BRCA2 carriers (HR 0.88, 95% CI 0.42 to 1.87; I² = 63%; P = 0.75; very low-certainty evidence). AUTHORS' CONCLUSIONS There is very low-certainty evidence that RRSO may increase overall survival and lower HGSC and breast cancer mortality for BRCA1 and BRCA2 carriers. Very low-certainty evidence suggests that RRSO reduces the risk of death from HGSC and breast cancer in women with BRCA1 mutations. Evidence for the effect of RRSO on HGSC and breast cancer in BRCA2 carriers was very uncertain due to low numbers. These results should be interpreted with caution due to questionable study designs, risk of bias profiles, and very low-certainty evidence. We cannot draw any conclusions regarding bone fracture incidence, quality of life, or severe adverse events for RRSO, or for effects of RRSO based on type and age at risk-reducing surgery. Further research on these outcomes is warranted to explore differential effects for BRCA1 or BRCA2 mutations.
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Affiliation(s)
- George U Eleje
- Faculty of Medicine, College of Health Sciences, Nnamdi Azikiwe University, Nnewi CampusEffective Care Research Unit, Department of Obstetrics and GynaecologyPMB 5001, NnewiNigeria
| | - Ahizechukwu C Eke
- Johns Hopkins University School of MedicineDivision of Maternal Fetal Medicine, Department of Gynecology and Obstetrics600 N Wolfe StreetPhipps 228BaltimoreUSA21287‐1228
| | - Ifeanyichukwu U Ezebialu
- Faculty of Clinical medicine, College of Medicine, Anambra State University AmakuDepartment of Obstetrics and GynaecologyAwkaNigeria
| | - Joseph I Ikechebelu
- Nnamdi Azikiwe University Teaching HospitalDepartment of Obstetrics/GynaecologyNnewiNigeria
| | - Emmanuel O Ugwu
- University of Nigeria Enugu Campus/University of Nigeria Teaching Hospital Ituko‐OzallaObstetrics and GynaecologyEnuguNigeria400001
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Casey MJ, Salzman TA. Reducing the Risk of Gynecologic Cancer in Hereditary Breast Ovarian Cancer Syndrome Mutation Carriers: Moral Dilemmas and the Principle of Double Effect. LINACRE QUARTERLY 2018; 85:225-240. [PMID: 30275608 PMCID: PMC6161234 DOI: 10.1177/0024363918788340] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Hereditary breast ovarian cancer (HBOC) syndrome is an autosomal dominant disease linked to mutations in the BRCA1 and BRCA2 genes in 90 percent of affected families. Female mutation carriers are highly susceptible to aggressive, often disseminated, usually fatal pelvic-abdominal carcinomatosis. This cancer risk can be markedly reduced by surgical removal of the internal gynecologic organs before the end of the fourth decade of life and by using estrogen-progestin formulations marketed for many years as combined oral contraceptives (COCs). Both risk-reducing methods are associated with unfavorable effects. Relying on the principle of double effect, this essay argues for the ethical justification of prophylactic surgery and the use of COC to reduce the risk of gynecologic cancer in HBOC syndrome mutation carriers. Summary: Hereditary breast ovarian cancer syndrome is an autosomal dominant disease linked to mutations in the BRCA1 and BRCA2 genes in most affected families. Female mutation carriers are highly susceptible to aggressive, often disseminated, usually fatal pelvic-abdominal carcinomatosis. This cancer risk can be markedly reduced by surgical removal of the internal gynecologic organs before the end of the fourth decade of life and by using estrogen-progestin formulations marketed for many years as combined oral contraceptives. Both risk-reducing methods are associated with unfavorable effects. Relying on the principle of double effect, this essay argues for the ethical justification for those unfavorable effects.
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BRCA1/2 testing: therapeutic implications for breast cancer management. Br J Cancer 2018; 119:141-152. [PMID: 29867226 PMCID: PMC6048046 DOI: 10.1038/s41416-018-0127-5] [Citation(s) in RCA: 136] [Impact Index Per Article: 19.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2017] [Revised: 04/10/2018] [Accepted: 04/24/2018] [Indexed: 12/15/2022] Open
Abstract
Testing for germline BRCA1/2 mutations has an established predictive role in breast cancer risk assessment. More recently, studies have also identified BRCA1/2 status as clinically relevant in the selection of therapy for patients already diagnosed with breast cancer. Emerging breast and ovarian cancer research indicate that BRCA status predicts responsiveness to platinum-based chemotherapy, as well as to inhibitors of poly(ADP-ribose) polymerase (PARP), owing to the ability of these interventions to inhibit DNA repair pathways. BRCA1/2 mutation testing thus has important and expanding roles in treatment planning for subsets of patients with breast cancer. Recent studies have demonstrated different activity of platinum salts in BRCA-mutated compared with non-BRCA-mutated breast cancer. Furthermore, phase II/III studies of single-agent PARP inhibitors (PARPi) have shown encouraging progression-free survival results in patients with BRCA1/2-mutated breast cancer, which led to the recent approval of olaparib, the first PARPi to be approved in breast cancer. Determining BRCA1/2 mutation status in this breast cancer subgroup could potentially expand treatment options beyond the current standard of taxane and anthracycline-based chemotherapy. Although attempts have been made to develop scoring systems that measure defects in homologous recombination repair pathways to predict response to platinum or PARPi, none have yet made it into clinical use. In this review, we summarise the recent and ongoing preclinical and clinical studies on the treatment of BRCA-associated breast cancer, and discuss efforts to identify other breast cancer patients who may be responsive to therapies effective in BRCA mutation carriers, including platinum-containing chemotherapy and PARPi.
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Uyar D, Neary J, Monroe A, Nugent M, Simpson P, Geurts JL. Implementation of a quality improvement project for universal genetic testing in women with ovarian cancer. Gynecol Oncol 2018; 149:565-569. [DOI: 10.1016/j.ygyno.2018.03.059] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2017] [Revised: 03/21/2018] [Accepted: 03/25/2018] [Indexed: 11/16/2022]
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Arora E, Masab M, Jindal V, Riaz I, Gupta S, Varadi G. Role of Poly Adenosine Diphosphate Ribose Polymerase Inhibitors in Advanced Stage Ovarian Cancer. Cureus 2018; 10:e2685. [PMID: 30050740 PMCID: PMC6059530 DOI: 10.7759/cureus.2685] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Ovarian cancer is one of the leading causes of death from gynecologic cancers. In this present era of cancer treatment, therapeutic options for patients with advanced or recurrent ovarian cancer are limited. The present standard of care treatment for advanced ovarian cancer is a platinum-based doublet chemotherapy (paclitaxel and carboplatin with or without bevacizumab) after a maximum attempt of surgical cytoreduction. However, there are no promising options for the management of patients with ovarian cancer refractory to the platinum-based chemotherapy. Therefore, newer, safe, and more effective treatment modalities are required for patients with advanced or recurrent ovarian cancer. Poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors have shown an impressive safety profile and anti-tumor efficacy in patients with breast cancer 1 and 2 (BRCA1 and BRCA2) gene-mutated ovarian cancer who were previously treated with the standard of care chemotherapy. We have done a detailed review of the literature to emphasize the role of PARP inhibitors in the treatment of advanced or relapsed ovarian cancer.
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Affiliation(s)
- Ena Arora
- Obstetrics and Gynecology, Civil Hospital Chandigarh, Chandigarh, IND
| | - Muhammad Masab
- Internal Medicine, Albert Einstein Medical Center, New York, USA
| | - Vishal Jindal
- Internal Medicine, St. Vincent Hospital Worcester, Worcester, USA
| | - Iqra Riaz
- Department of Medicine, Mayo Hospital, King Edward Medical University, Lahore, Pakistan
| | - Sorab Gupta
- Hematology and Oncology, Albert Einstein Medical Center, New York, USA
| | - Gabor Varadi
- Hematology and Oncology, Albert Einstein Medical Center, New York, USA
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Smith S, Marino I, Schaller J, Arnell C, Moyes K, Manley S. Optimization of quality assurance to increase clinical utility and cost effectiveness of hereditary cancer testing. Per Med 2018; 14:213-220. [PMID: 29767585 DOI: 10.2217/pme-2016-0091] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
AIM To evaluate one laboratory's hereditary cancer testing clinical quality assurance (QA) process to minimize test-ordering errors. METHODS The proportion of tests canceled/revised due to pre-analytic QA processes or provider consultation prior to test ordering were determined and the resulting health cost savings were estimated. RESULTS Over 2000 genetic test orders were canceled/revised over a 1-year period due to the laboratory QA process, saving US$5,801,832 in healthcare costs. Consultation with healthcare providers prior to submitting genetic test requests resulted in 37 canceled/revised test orders in a 2-week period, which extrapolates to a savings of US$3,049,098 over 1 year. CONCLUSION QA processes can contribute to the curtailment of healthcare costs through canceling or revising test orders.
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Affiliation(s)
- Serenedy Smith
- Myriad Genetic Laboratories, Inc., Salt Lake City, UT, USA
| | - Ingrid Marino
- Myriad Genetic Laboratories, Inc., Salt Lake City, UT, USA
| | | | | | - Kelsey Moyes
- Myriad Genetic Laboratories, Inc., Salt Lake City, UT, USA
| | - Susan Manley
- Myriad Genetic Laboratories, Inc., Salt Lake City, UT, USA
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Breadth of Genetic Testing Selected by Patients at Risk of Hereditary Breast and Ovarian Cancer. Int J Gynecol Cancer 2018; 28:26-33. [PMID: 28930807 DOI: 10.1097/igc.0000000000001122] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023] Open
Abstract
OBJECTIVE The aim of this study was to evaluate the ability of patients at risk of hereditary breast and ovarian cancer (HBOC) syndrome to select the extent of genetic testing personally preferred and the impact of demographic factors on the breadth of testing pursued. METHODS A single-institution cohort was enumerated consisting of patients referred for clinical genetic counseling secondary to risk of HBOC syndrome. This was a retrospective study of consecutive patients seen for genetic counseling; all patients completed an epidemiologic questionnaire and provided personal and family medical histories. Patients meeting guidelines for testing were offered testing at 3 levels: single gene/condition (Single), small panels with highly penetrant genes (Plus), and large panels with high and moderately penetrant genes (Next). Associations between personal or family-related factors and breadth of testing selected were investigated. Continuous and categorical variables were compared using Student t and χ tests, as appropriate. Joint classification tables were used to test for effect modification, and a log-binomial model was used to compute rate ratios (RR) with a threshold of P < 0.05 considered significant. RESULTS We identified 253 patients who underwent genetic counseling for HBOC syndrome. Most patients were personally affected by cancer (63.6%), reported at least some college (79.2%), met the National Comprehensive Cancer Network guidelines for BRCA testing (94.5%), and opted to undergo genetic testing (94.1%). Most (84.9%) patients opted for panel testing. An increased likelihood of choosing Next-level testing was found to be associated with patients having any college experience (RR, 1.53; 95% confidence interval, 1.02-2.30), as well as being unaffected by cancer (RR, 1.30; 95% confidence interval, 1.03-1.64). CONCLUSIONS Clinical genetic counseling is a highly specialized service, which should be provided to patients at risk of hereditary cancer syndromes. Although some epidemiologic factors can predict a patient's preference for testing breadth, patients were sufficiently able to self-identify the level of testing they were comfortable with after receiving genetic counseling. Most practitioners do not have the time or expertise to provide the degree of counseling needed to enable and empower patients to choose the level of testing they are comfortable with. When available, referral to genetic counselors remains an important component of comprehensive care for women with a personal or family history of cancer suggestive of hereditary risk.
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Campo-Engelstein L. BRCA Previvors: Medical and Social Factors That Differentiate Them From Previvors With Other Hereditary Cancers. BIOÉTHIQUEONLINE 2018. [DOI: 10.7202/1044611ar] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
In this paper, I outline some of the reasons why BRCA “previvors” (i.e., “survivors of a predisposition to cancer”) are different from previvors with other hereditary cancers. I examine how the absence of a standard of care for breast cancer risk for women with a BRCA mutation, coupled with a broad range of genetic penetrance and lower mortality, makes BRCA different than other hereditary cancers that have clear and established guidelines. In addition to these medical differences, social factors like the cultural prominence of breast cancer and the social significance of breasts have engendered a more complicated individual previvor identity for and cultural response to women with a BRCA mutation.
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Affiliation(s)
- Lisa Campo-Engelstein
- Alden March Bioethics Institute, OBGYN Department, Albany Medical College, Albany, NY, USA
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Hull LE, Haas JS, Simon SR. Provider Discussions of Genetic Tests With U.S. Women at Risk for a BRCA Mutation. Am J Prev Med 2018; 54:221-228. [PMID: 29241717 DOI: 10.1016/j.amepre.2017.10.015] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2017] [Revised: 09/05/2017] [Accepted: 10/20/2017] [Indexed: 01/26/2023]
Abstract
INTRODUCTION The U.S. Preventive Services Task Force recommends that primary care providers screen unaffected women with a family history of BRCA mutation-associated cancers, but without a personal history of BRCA-related cancer, for referral to genetic counseling and potential genetic testing. METHODS The 2015 National Health Interview Survey was analyzed in January 2017 to determine the rates at which unaffected adult women with a positive family history of BRCA-related cancers, assessed using the Family History Screen-7, reported discussing genetic testing with a provider, using genetic counseling services, and having genetic testing for increased cancer risk. Clinical correlates associated with these outcomes were assessed using multivariable logistic regression (AOR with 95% CI). RESULTS Among unaffected Family History Screen-7 screen-positive women, 9.5% reported discussing genetic testing with a provider, 5.1% reported genetic counseling, and 2.7% reported uptake of genetic testing. Younger women (aged 18-39 and 40-49 years) were more likely to discuss genetic testing than women aged ≥60 years (AOR=1.50, 95% CI=1.09, 2.06 and AOR=1.64, 95% CI=1.15, 2.33, respectively). Women of black race (AOR=1.50, 95% CI=1.09, 2.07) and women with greater than a high school education (AOR=1.85, 95% CI=1.41, 2.43) were more likely to discuss genetic testing than women of white race and women with a high school education or less, respectively. Among a higher risk subgroup with an even stronger family history of BRCA-associated cancers, 18.5% of women reported discussions. CONCLUSIONS Despite a decade-old U.S. Preventive Services Task Force recommendation, few unaffected women at risk for BRCA-associated cancer report discussing genetic testing with a provider.
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Affiliation(s)
- Leland E Hull
- Center for Healthcare Organization and Implementation Research, VA Boston Healthcare System, Boston, Massachusetts; Section of General Internal Medicine, VA Boston Healthcare System, Boston, Massachusetts.
| | - Jennifer S Haas
- Division of General Internal Medicine and Primary Care, Brigham and Women's Hospital, Boston, Massachusetts
| | - Steven R Simon
- Center for Healthcare Organization and Implementation Research, VA Boston Healthcare System, Boston, Massachusetts; Geriatrics and Extended Care Service, VA Boston Healthcare System, Boston, Massachusetts
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Altman AM, Hui JYC, Tuttle TM. Quality-of-life implications of risk-reducing cancer surgery. Br J Surg 2018; 105:e121-e130. [DOI: 10.1002/bjs.10725] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2017] [Accepted: 09/04/2017] [Indexed: 01/15/2023]
Abstract
Abstract
Background
Modern advances in genetic sequencing techniques have allowed for increased availability of genetic testing for hereditary cancer syndromes. Consequently, more people are being identified as mutation carriers and becoming aware of their increased risk of malignancy. Testing is commonplace for many inheritable cancer syndromes, and with that comes the knowledge of being a gene carrier for some patients. With increased risk of malignancy, many guidelines recommend that gene carriers partake in risk reduction strategies, including risk-reducing surgery for some syndromes. This review explores the quality-of-life consequences of genetic testing and risk-reducing surgery.
Methods
A narrative review of PubMed/MEDLINE was performed, focusing on the health-related quality-of-life implications of surgery for hereditary breast and ovarian cancer, familial adenomatous polyposis and hereditary diffuse gastric cancer.
Results
Risk-reducing surgery almost uniformly decreases cancer anxiety and affects patients' quality of life.
Conclusion
Although the overwhelming quality-of-life implications of surgery are neutral to positive, risk-reducing surgery is irreversible and can be associated with short- and long-term side-effects.
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Affiliation(s)
- A M Altman
- Department of Surgery, University of Minnesota, Minneapolis, Minnesota, USA
| | - J Y C Hui
- Department of Surgery, University of Minnesota, Minneapolis, Minnesota, USA
| | - T M Tuttle
- Department of Surgery, University of Minnesota, Minneapolis, Minnesota, USA
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