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Matsumoto M, Den H, Miura S, Harada A, Nomura H, Arai M, Kumamaru H, Nakamura S, Sekine M, Miura K. The impact of public insurance on RRSO for HBOC in Japan: a nationwide data study. J Hum Genet 2025:10.1038/s10038-025-01326-0. [PMID: 40399479 DOI: 10.1038/s10038-025-01326-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Revised: 02/09/2025] [Accepted: 02/16/2025] [Indexed: 05/23/2025]
Abstract
In Japan, risk management based on genetic disposition, such as risk-reducing surgery for hereditary breast and ovarian cancer (HBOC), is covered by public insurance only for some cancer patients. However, non-cancer clients are forced to pay a high co-payment. In this study, we examined the impact of risk-reducing salpingo-oophorectomy (RRSO), before and after the April 2020 public insurance coverage, using nationwide data from the Japanese Organization of Hereditary Breast and Ovarian Cancer. The period from March 2006 to March 2020 was defined as before insurance coverage (Pre), and the period from April 2020 to August 2021 was defined as after insurance coverage (Post). In addition, the period from April 2018 to March 2020 was designated as special (short-Pre) to coincide with the post-insurance coverage period. Of the 383 breast cancer patients who underwent genetic testing at Short-Pre, 42 (11.0%) underwent RRSO during that period. Of the 623 breast cancer patients who underwent genetic testing at Post, 142 (22.8%) underwent RRSO during that period. Significantly, this comparison shows an increase in RRSO rates in Post. Separating BRCA1 and BRCA2 also significantly increased RRSO in Post. This nationwide survey suggests that if RRSO is covered by insurance in Japan, the implementation rate will increase. As the number of cases increases in the future, the impact of insurance coverage will become clearer. If the insurance coverage for RRSO in Japan is determined to be useful, this information can be used to expand coverage for those who have not yet developed the disease.
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Affiliation(s)
- Megumi Matsumoto
- Department of Breast Endocrine Surgery, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki, Japan
| | - Hiroki Den
- Department of Hygiene, Public Health, and Preventative Medicine, Showa University School of Medicine, Tokyo, Japan
| | - Shoko Miura
- Department of Obstetrics and Gynecology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Ayumi Harada
- Department of Obstetrics and Gynecology, Nagasaki University Hospital, Nagasaki, Japan
| | - Hiroyuki Nomura
- Department of Obstetrics and Gynecology, Tokai University School of Medicine, Isehara, Japan
| | - Masami Arai
- Department of Clinical Genetics, Juntendo University, Graduate School of Medicine, Tokyo, Japan
| | - Hiraku Kumamaru
- Department of Healthcare Quality Assessment, The University of Tokyo Graduate School of Medicine, Tokyo, Japan
| | - Seigo Nakamura
- Division of Breast Surgical Oncology, Department of Surgery, Showa University School of Medicine Institute for Clinical Genetics and Genomics Showa University, Tokyo, Japan
| | - Masayuki Sekine
- Department of Obstetrics and Gynecology, Graduate School of Medical Science University of the Ryukyus, Okinawa, Japan.
| | - Kiyonori Miura
- Department of Obstetrics and Gynecology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
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Assaf W, Qarawani A, Abboud Y, Shalabna E, Nahshon C, Zilberlicht A, Reiss A, Schmidt M, Segev Y. Pathology results of risk-reducing salpingo-oophorectomy in BRCA1/2 carriers and long-term clinical outcomes. Int J Gynaecol Obstet 2025. [PMID: 40231745 DOI: 10.1002/ijgo.70110] [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: 12/16/2024] [Revised: 03/08/2025] [Accepted: 03/18/2025] [Indexed: 04/16/2025]
Abstract
INTRODUCTION BRCA1/2 mutation carriers have a lifetime ovarian cancer risk of 40%-45% for BRCA1 and 15%-20% for BRCA2. The most effective risk-reduction strategy for women with known BRCA mutations remains bilateral risk-reducing salpingo-oophorectomy (RRSO), which reduces the risk by 80%. The primary objective of this study is to assess the long-term incidence of primary peritoneal carcinoma (PPC) following RRSO and to evaluate the occurrence of premalignant and malignant lesions. METHODS This retrospective cohort study followed BRCA1/2-positive patients who underwent RRSO, using data from two medical centers in Haifa Israel between 2002 and 2023. Data collected included demographic characteristics and pathology results post-surgery. Outcomes included rates of occult cancer (OC), serous tubal intraepithelial carcinoma (STIC), and PPC. RESULTS A total of 214 women underwent RRSO. Of these, 126 (58.8%) had a BRCA1 mutation, 76 (35.5%) had a BRCA2 mutation, and 12 (5.6%) carried both BRCA1 and BRCA2 mutations. During a mean follow-up of 122.4 months (SD ± 84.0), three patients (1.5%) developed PPC. OC was identified in 13 patients (6.1%) during RRSO. Out of the 13 OC patients, eight (61.5%) were classified as stage 1. The overall survival for the OC population was 117.2 ± 55.9 months. STIC was detected in two patients. CONCLUSION In this large retrospective analysis of BRCA carriers who underwent RRSO, we confirmed that long-term follow-up is crucial for BRCA mutation carriers undergoing RRSO, as malignancies can still arise over time. In our study, the incidence of PPC was 1.5%, highlighting the need for extended surveillance. These findings underscore the importance of meticulous surgical protocols, expert pathology review, and ongoing monitoring to optimize patient outcomes.
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Affiliation(s)
- Wisam Assaf
- Department of Obstetrics and Gynecology, Lady Davis Carmel Medical Center, Technion University, Rappaport Faculty of Medicine, Haifa, Israel
- Rappaport Faculty of Medicine, Technion-Israel Institution of Technology, Haifa, Israel
| | - Amalfi Qarawani
- Rappaport Faculty of Medicine, Technion-Israel Institution of Technology, Haifa, Israel
| | - Yousef Abboud
- Rappaport Faculty of Medicine, Technion-Israel Institution of Technology, Haifa, Israel
- Department of Obstetrics and Gynecology, Rambam Health Care Campus, Technion University, Rappaport Faculty of Medicine, Haifa, Israel
| | - Eiman Shalabna
- Rappaport Faculty of Medicine, Technion-Israel Institution of Technology, Haifa, Israel
| | - Chen Nahshon
- Department of Obstetrics and Gynecology, Lady Davis Carmel Medical Center, Technion University, Rappaport Faculty of Medicine, Haifa, Israel
- Rappaport Faculty of Medicine, Technion-Israel Institution of Technology, Haifa, Israel
| | - Ariel Zilberlicht
- Department of Obstetrics and Gynecology, Lady Davis Carmel Medical Center, Technion University, Rappaport Faculty of Medicine, Haifa, Israel
- Rappaport Faculty of Medicine, Technion-Israel Institution of Technology, Haifa, Israel
| | - Ari Reiss
- Rappaport Faculty of Medicine, Technion-Israel Institution of Technology, Haifa, Israel
- Department of Obstetrics and Gynecology, Emek Medical Center, Rappaport Faculty of Medicine, Technion University, Haifa, Israel
| | - Meirav Schmidt
- Department of Obstetrics and Gynecology, Lady Davis Carmel Medical Center, Technion University, Rappaport Faculty of Medicine, Haifa, Israel
- Rappaport Faculty of Medicine, Technion-Israel Institution of Technology, Haifa, Israel
| | - Yakir Segev
- Department of Obstetrics and Gynecology, Lady Davis Carmel Medical Center, Technion University, Rappaport Faculty of Medicine, Haifa, Israel
- Rappaport Faculty of Medicine, Technion-Israel Institution of Technology, Haifa, Israel
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Stroot IAS, Bart J, Hollema H, Wagner MM, Yigit R, van Doorn HC, de Hullu JA, Gaarenstroom KN, van Beurden M, van Lonkhuijzen LRCW, Slangen BFM, Zweemer RP, Gómez Garcia EB, Ausems MGEM, Komdeur FL, van Asperen CJ, Adank MA, Wevers MR, Hooning MJ, Mourits MJE, de Bock GH. High-grade serous carcinoma occurring after risk-reducing salpingo-oophorectomy in BRCA1/2 germline pathogenic variant carriers. J Natl Cancer Inst 2025; 117:719-727. [PMID: 39579093 DOI: 10.1093/jnci/djae300] [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: 09/25/2024] [Revised: 10/29/2024] [Accepted: 11/12/2024] [Indexed: 11/25/2024] Open
Abstract
BACKGROUND Risk-reducing salpingo-oophorectomy (RRSO) effectively prevents high-grade serous carcinoma (HGSC) in BRCA1/2 germline pathogenic variant (GPV) carriers. Still, some women develop HGSC after RRSO without pathological findings. This study assessed long-term incidence and risk factors for developing HGSC after RRSO without pathological findings. METHODS BRCA1/2 GPV carriers were selected from the Hereditary Breast and Ovarian cancer in the Netherlands (HEBON) cohort. Follow-up data for HGSC after RRSO were obtained from the Dutch Nationwide Pathology Databank (PALGA) and confirmed by histopathological review. Cumulative incidence rates of HGSC were calculated using Kaplan-Meier analyses. A Cox proportional hazards model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for factors associated with an increased risk of HGSC after RRSO without pathological findings. RESULTS A total of 2519 women were included, with a median follow-up of 13.4 years (range: 0.0-27.6 years). The 20-year cumulative incidence rate of HGSC was 1.5% (95% CI = 0.0 to 2.1) for BRCA1 and 0.2% (95% CI = 0.0 to 1.4) for BRCA2 GPV carriers. All women who developed HGSC underwent RRSO after the recommended age. Incomplete embedding of the RRSO specimen (HR = 4.2, 95% CI = 1.4 to 12.6), higher age at RRSO (HR per year = 1.1, 95% CI = 1.0 to 1.1), and carrying a BRCA1 GPV (HR = 12.1, 95% CI = 1.6 to 91.2) were associated with increased risk of HGSC. CONCLUSIONS In BRCA1/2 GPV carriers, long-term incidence of HGSC after RRSO without pathological findings was low. Strict adherence to guidelines regarding timely RRSO followed by complete specimen embedding can further reduce the risk of HGSC in the years after RRSO.
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Affiliation(s)
- Iris A S Stroot
- Department of Gynecologic Oncology, University of Groningen, University Medical Centre Groningen, Groningen 9700 RB, the Netherlands
- Department of Epidemiology, University of Groningen, University Medical Centre Groningen, Groningen 9700 RB, the Netherlands
| | - Joost Bart
- Department of Pathology, University of Groningen, University Medical Centre Groningen, Groningen 9700 RB, the Netherlands
| | - Harry Hollema
- Department of Pathology, University of Groningen, University Medical Centre Groningen, Groningen 9700 RB, the Netherlands
| | - Marise M Wagner
- Department of Gynecologic Oncology, University of Groningen, University Medical Centre Groningen, Groningen 9700 RB, the Netherlands
| | - Refika Yigit
- Department of Gynecologic Oncology, University of Groningen, University Medical Centre Groningen, Groningen 9700 RB, the Netherlands
| | - Helena C van Doorn
- Department of Gynecologic Oncology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam 3015 GD, the Netherlands
| | - Joanne A de Hullu
- Department of Obstetrics and Gynecology, Radboud University Medical Center, Nijmegen 6525 GA, the Netherlands
| | - Katja N Gaarenstroom
- Department of Obstetrics and Gynecology, Leiden University Medical Center, Leiden 2333 ZA, the Netherlands
| | - Marc van Beurden
- Department of Gynecology, Antoni van Leeuwenhoek, Amsterdam 1066 CX, the Netherlands
| | - Luc R C W van Lonkhuijzen
- Department of Gynecologic Oncology, Amsterdam University Medical Center-Center for Gynecological Oncology Amsterdam, Amsterdam 1105 AZ, the Netherlands
| | - Brigitte F M Slangen
- Department of Gynecology, GROW Research Institute for Oncology and Reproduction, Maastricht University Medical Center, Maastricht 6229 HX, the Netherlands
| | - Ronald P Zweemer
- Department of Gynecologic Oncology, University Medical Center Utrecht, Utrecht 3584 CX, the Netherlands
| | - Encarna B Gómez Garcia
- Department of Clinical Genetics, GROW Research Institute for Oncology and Reproduction, University Medical Center Maastricht, Maastricht 6229 HX, the Netherlands
| | - Margreet G E M Ausems
- Department of Genetics, Division Laboratories, Pharmacy and Biomedical Genetics, University Medical Center Utrecht, Utrecht 3584 CX, the Netherlands
| | - Fenne L Komdeur
- Department of Human Genetics, Amsterdam University Medical Center, Amsterdam 1105 AZ, the Netherlands
| | - Christi J van Asperen
- Department of Clinical Genetics, Leiden University Medical Center, Leiden 2333 ZA, the Netherlands
| | - Muriel A Adank
- Department of Clinical Genetics, Netherlands Cancer Institute, Amsterdam 1066 CX, the Netherlands
| | - Marijke R Wevers
- Department of Clinical Genetics, Radboud University Medical Center, Nijmegen 6525 GA, the Netherlands
| | - Maartje J Hooning
- Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam 3015 GD, the Netherlands
| | - Marian J E Mourits
- Department of Gynecologic Oncology, University of Groningen, University Medical Centre Groningen, Groningen 9700 RB, the Netherlands
| | - Geertruida H de Bock
- Department of Epidemiology, University of Groningen, University Medical Centre Groningen, Groningen 9700 RB, the Netherlands
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Mo L, Deng M, Adhav R, Chan Y, Lei JH, Su SM, Zhang X, An T, Liu J, Li J, Shu X, Xu J, Wang Y, Chen L, Man YG, Shao NY, Xiang T, Deng CX, Xu X. Oncogenic activation of SMYD3-SHCBP1 promotes breast cancer development and is coupled with resistance to immune therapy. Cell Death Dis 2025; 16:220. [PMID: 40157910 PMCID: PMC11954966 DOI: 10.1038/s41419-025-07570-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2025] [Revised: 03/10/2025] [Accepted: 03/18/2025] [Indexed: 04/01/2025]
Abstract
Breast cancer initiation and progression are driven by various oncogenic factors and their effects on the surrounding microenvironments. Through integrative analysis of ChIP-sequencing and RNA-sequencing with fast proliferating mammary epithelial cells from pregnant Brca1MKO and wild type (WT) mice, we found that elevated Smyd3-Shcbp1 signaling is featured with activation of the Ras-MAPK pathway and increased transcription activity in both premalignant mammary epithelium and tumor cells. Smyd3-Shcbp1 signaling shapes the tumor immunosuppressive microenvironment (TIME) and is associated with immune therapy resistance to PD1 antibody treatment. Trametinib, a potent inhibitor of MEK/MAPK, could reverse the expression of Smyd3 and Shcbp1 in both Brca1 mutant and WT tumor bearing mice. We further demonstrated that the combinatory treatment of trametinib together with PD1 antibody enhances the function of effector T cells, sensitizing tumors with elevated Smyd3 and Shcbp1 signaling to αPD1 treatment. This study advances the understanding of breast tumor progression and provides a new selective strategy for breast cancer patients.
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Affiliation(s)
- Lihua Mo
- Cancer Centre, Faculty of Health Sciences, University of Macau, Macau SAR, China
- Centre for Precision Medicine Research and Training, Faculty of Health Sciences, University of Macau, Macau SAR, China
- Ministry of Education Frontiers Science Center for Precision Oncology, University of Macau, Taipa, Macau SAR, China
| | - Min Deng
- Cancer Centre, Faculty of Health Sciences, University of Macau, Macau SAR, China
- Centre for Precision Medicine Research and Training, Faculty of Health Sciences, University of Macau, Macau SAR, China
- Ministry of Education Frontiers Science Center for Precision Oncology, University of Macau, Taipa, Macau SAR, China
| | - Ragini Adhav
- Cancer Centre, Faculty of Health Sciences, University of Macau, Macau SAR, China
- Centre for Precision Medicine Research and Training, Faculty of Health Sciences, University of Macau, Macau SAR, China
| | - Yuni Chan
- Cancer Centre, Faculty of Health Sciences, University of Macau, Macau SAR, China
- Centre for Precision Medicine Research and Training, Faculty of Health Sciences, University of Macau, Macau SAR, China
| | - Josh Haipeng Lei
- Cancer Centre, Faculty of Health Sciences, University of Macau, Macau SAR, China
- Centre for Precision Medicine Research and Training, Faculty of Health Sciences, University of Macau, Macau SAR, China
- Ministry of Education Frontiers Science Center for Precision Oncology, University of Macau, Taipa, Macau SAR, China
| | - Sek Man Su
- Cancer Centre, Faculty of Health Sciences, University of Macau, Macau SAR, China
- Centre for Precision Medicine Research and Training, Faculty of Health Sciences, University of Macau, Macau SAR, China
- Ministry of Education Frontiers Science Center for Precision Oncology, University of Macau, Taipa, Macau SAR, China
| | - Xin Zhang
- Cancer Centre, Faculty of Health Sciences, University of Macau, Macau SAR, China
- Centre for Precision Medicine Research and Training, Faculty of Health Sciences, University of Macau, Macau SAR, China
- Ministry of Education Frontiers Science Center for Precision Oncology, University of Macau, Taipa, Macau SAR, China
| | - Tingting An
- Cancer Centre, Faculty of Health Sciences, University of Macau, Macau SAR, China
- Centre for Precision Medicine Research and Training, Faculty of Health Sciences, University of Macau, Macau SAR, China
- Ministry of Education Frontiers Science Center for Precision Oncology, University of Macau, Taipa, Macau SAR, China
| | - Jianlin Liu
- Cancer Centre, Faculty of Health Sciences, University of Macau, Macau SAR, China
- Centre for Precision Medicine Research and Training, Faculty of Health Sciences, University of Macau, Macau SAR, China
- Ministry of Education Frontiers Science Center for Precision Oncology, University of Macau, Taipa, Macau SAR, China
| | - Jianjie Li
- Cancer Centre, Faculty of Health Sciences, University of Macau, Macau SAR, China
- Centre for Precision Medicine Research and Training, Faculty of Health Sciences, University of Macau, Macau SAR, China
- Ministry of Education Frontiers Science Center for Precision Oncology, University of Macau, Taipa, Macau SAR, China
| | - Xiaodong Shu
- Cancer Centre, Faculty of Health Sciences, University of Macau, Macau SAR, China
- Centre for Precision Medicine Research and Training, Faculty of Health Sciences, University of Macau, Macau SAR, China
- Ministry of Education Frontiers Science Center for Precision Oncology, University of Macau, Taipa, Macau SAR, China
| | - Jun Xu
- Cancer Centre, Faculty of Health Sciences, University of Macau, Macau SAR, China
- Centre for Precision Medicine Research and Training, Faculty of Health Sciences, University of Macau, Macau SAR, China
- Ministry of Education Frontiers Science Center for Precision Oncology, University of Macau, Taipa, Macau SAR, China
| | - Yuqing Wang
- Cancer Centre, Faculty of Health Sciences, University of Macau, Macau SAR, China
- Centre for Precision Medicine Research and Training, Faculty of Health Sciences, University of Macau, Macau SAR, China
- Ministry of Education Frontiers Science Center for Precision Oncology, University of Macau, Taipa, Macau SAR, China
| | - Lin Chen
- Laboratory of Wound Repair and Rehabilitation Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Daping Hospital, Army Medical University, Chongqing, 400042, China
| | - Yan-Gao Man
- Department of Pathology, Hackensack Meridian School of Medicine, Nutley, NJ, USA
| | - Ning-Yi Shao
- Cancer Centre, Faculty of Health Sciences, University of Macau, Macau SAR, China
- Centre for Precision Medicine Research and Training, Faculty of Health Sciences, University of Macau, Macau SAR, China
- Ministry of Education Frontiers Science Center for Precision Oncology, University of Macau, Taipa, Macau SAR, China
| | - Tingxiu Xiang
- Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing, 400030, China
| | - Chu-Xia Deng
- Cancer Centre, Faculty of Health Sciences, University of Macau, Macau SAR, China.
- Centre for Precision Medicine Research and Training, Faculty of Health Sciences, University of Macau, Macau SAR, China.
- Ministry of Education Frontiers Science Center for Precision Oncology, University of Macau, Taipa, Macau SAR, China.
- Zhuhai UM Science & Technology Research Institute, Hengqin, China.
| | - Xiaoling Xu
- Cancer Centre, Faculty of Health Sciences, University of Macau, Macau SAR, China.
- Centre for Precision Medicine Research and Training, Faculty of Health Sciences, University of Macau, Macau SAR, China.
- Ministry of Education Frontiers Science Center for Precision Oncology, University of Macau, Taipa, Macau SAR, China.
- Zhuhai UM Science & Technology Research Institute, Hengqin, China.
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Ain Q, O'Connell RL, Swarnkar P, McVeigh T, George A, Tasoulis MK, Gui GP, Wiggins J, Khan AA, Krupa KD, Barry PA, Banerjee S, Rusby JE. Breast cancer outcomes in women with ovarian cancer and a pathogenic germline BRCA mutation. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2025; 51:109380. [PMID: 39724722 DOI: 10.1016/j.ejso.2024.109380] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Revised: 11/03/2024] [Accepted: 11/10/2024] [Indexed: 12/28/2024]
Abstract
BACKGROUND Women with ovarian cancer (OC) and a pathogenic variant in the BRCA1 or BRCA2 genes are at increased risk of developing breast cancer (BC). Evidence for long term outcomes in these patients who undergo bilateral risk reduction mastectomy (RRM) after ovarian cancer is sparse. The aim of this study was to analyse the long-term breast cancer-related outcomes of patients who have been diagnosed with ovarian cancer and found to have BRCA1 or 2 pathogenic variants. METHODS Local approval was granted. The hospital clinical genetics database was interrogated to identify women who have been diagnosed with OC and a germline BRCA1/2 pathogenic variant between January 2010-March 2020. Patient demographics, OC treatment as well as any BC related information was analysed. RESULTS 148 women were diagnosed with OC and a pathogenic variant in BRCA1/2 in the study period. 47 patients were excluded as they did not have treatment at our institution. 101 patients were included. The median age at diagnosis of OC was 52 years (IQR 46-61). Eighty-four (82 %) were FIGO stage 3 or 4 OC. At a median follow-up of 63 months (IQR 39-94), 55 (54.4 %) women had been diagnosed with a recurrence of ovarian cancer and 38 (37 %) women have died. Twenty-one (21 %) women were diagnosed with BC. 13 (12.9 %) had BC before OC, 4 after and 4 synchronous with OC. Of the remaining patients who did not have BC, 6 underwent bilateral risk reduction mastectomy (RRM) after treatment for OC. DISCUSSION Risk of disease recurrence and death due to stage 3 and 4 ovarian cancer remained high in this time period. RRM can be undertaken in carefully selected patients, however we would recommend reserving this for women who have favourable OC disease prognosis.
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Affiliation(s)
- Quratul Ain
- Breast Surgery Unit, The Royal Marsden NHS Foundation Trust, London, UK
| | - Rachel L O'Connell
- Breast Surgery Unit, The Royal Marsden NHS Foundation Trust, London, UK; Institute of Cancer Research, London, UK
| | - Parinita Swarnkar
- Breast Surgery Unit, The Royal Marsden NHS Foundation Trust, London, UK
| | - Terri McVeigh
- Genetics Department, The Royal Marsden NHS Foundation Trust, London, UK
| | - Angela George
- Genetics Department, The Royal Marsden NHS Foundation Trust, London, UK; Medical Oncology Unit, The Royal Marsden NHS Foundation Trust, London, UK
| | - Marios K Tasoulis
- Breast Surgery Unit, The Royal Marsden NHS Foundation Trust, London, UK; Institute of Cancer Research, London, UK
| | - Gerald Ph Gui
- Breast Surgery Unit, The Royal Marsden NHS Foundation Trust, London, UK
| | - Jennifer Wiggins
- Genetics Department, The Royal Marsden NHS Foundation Trust, London, UK
| | - Aadil A Khan
- Institute of Cancer Research, London, UK; Plastic Surgery Unit, The Royal Marsden NHS Foundation Trust, London, UK
| | | | - Peter A Barry
- Breast Surgery Unit, The Royal Marsden NHS Foundation Trust, London, UK; Institute of Cancer Research, London, UK
| | - Susana Banerjee
- Institute of Cancer Research, London, UK; Gynaecology Unit, The Royal Marsden NHS Foundation Trust, London, UK
| | - Jennifer E Rusby
- Breast Surgery Unit, The Royal Marsden NHS Foundation Trust, London, UK; Institute of Cancer Research, London, UK.
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6
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Hyldebrandt HK, Stormorken AT, Vitelli V, Mæhle L, Schlichting E, Grindedal EM. Risk reducing mastectomy in Norwegian BRCA1/2 carriers. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2025; 51:109571. [PMID: 39765192 DOI: 10.1016/j.ejso.2024.109571] [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: 09/24/2024] [Revised: 12/10/2024] [Accepted: 12/30/2024] [Indexed: 03/17/2025]
Abstract
BACKGROUND Risk reducing mastectomy (RRM) is an option for women with pathogenic germline variants in BRCA1 or BRCA2 (BRCA1/2). This study investigates and compares RRM-uptake among Norwegian BRCA1/2 carriers from 2008 to 2021, temporal trends, and incidence of breast cancer (BC) after surgery. METHODS BRCA1/2 carriers without prior breast or ovarian cancer, tested at Oslo University Hospital between January 1st, 2008 and December 31st, 2021 were included in the study. Data on RRM was obtained from The Norwegian Patient Registry. RRM-uptake, time from genetic testing (GT) to RRM, and RRM-uptake 2- and 5-years post-GT was calculated for all carriers, according to gene and age at GT. RRM-uptake was compared for those tested in 2008/2009 versus 2015/2016. BC diagnoses post-RRM was collected from The Cancer Registry of Norway. RESULTS In total, 1237 BRCA1/2 carriers were included, 679 (54.9 %) BRCA1 and 558 (45.1 %) BRCA2. Six hundred and four (48.8 %) had chosen RRM, 370 (54.5 %) BRCA1 and 234 (42.0 %) BRCA2 (p < 0.001). Mean age at RRM was 40.1 for BRCA1 and 44.6 for BRCA2 (p < 0.001). Mean time from GT to RRM was 2.3 years for BRCA1 and 3 years for BRCA2 (p < 0.001). Women tested in 2015/2016 were 2.6 times more likely to choose RRM compared to those tested in 2008/2009. Two out of the 604 (0.3 %) had developed BC post-RRM. CONCLUSION Nearly half of BRCA1/2 carriers had chosen RRM, with increasing uptake since 2008. Compared to BRCA2 carriers, more BRCA1 carriers chose RRM, were operated at a younger age and sooner after GT. Post-RRM BC incidence was low.
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Affiliation(s)
- Hanne Kjensli Hyldebrandt
- Department of Medical Genetics, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
| | | | - Valeria Vitelli
- Oslo Centre for Biostatistics and Epidemiology, Department of Biostatistics, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
| | - Lovise Mæhle
- Department of Medical Genetics, Oslo University Hospital, Oslo, Norway
| | - Ellen Schlichting
- Department of Cancer Surgery, Oslo University Hospital, Oslo, Norway
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7
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Lee YJ, Kim JH, Kim YJ, Chang YJ, Kong SY, Yoo CW, Lee DO, Seo SS, Kang S, Park SY, Lim MC. The pathologic and clinical outcomes of risk-reducing salpingo-oophorectomy in asymptomatic carriers of homologous recombination repair gene mutation. J Gynecol Oncol 2025; 36:e15. [PMID: 39028150 PMCID: PMC11964960 DOI: 10.3802/jgo.2025.36.e15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 05/16/2024] [Accepted: 06/25/2024] [Indexed: 07/20/2024] Open
Abstract
OBJECTIVE To investigate the prevalence of pathological findings and clinical outcomes of risk-reducing salpingo-oophorectomy (RRSO) in asymptomatic carriers with germline homologous recombination repair (HRR) gene pathogenic/likely pathogenic variants (PV/LPV). METHODS This retrospective study enrolled asymptomatic carriers with germline HR gene PV/LPV who underwent RRSO between 2006 and 2022 at the National Cancer Center in Korea. Clinical characteristics, including history of breast cancer, family history of ovarian/breast cancer, parity, and oral contraceptive use, were analyzed. RESULTS Of the 255 women who underwent RRSO, 129 (50.6%) had PV/LPV in BRCA1, 121 (47.5%) in BRCA2, and 2 (0.7%) had both BRCA1 and BRCA2 PV/LPV. In addition, 1 carried PV/LPV in RAD51D, and 2 in BRIP1. Among the BRCA1/2 PV/LPV carriers, occult neoplasms were identified in 3.5% of patients: serous tubal intraepithelial carcinoma (1.1%, n=3), fallopian tubal cancers (0.8%, n=2), ovarian cancer (1.2%, n=3), and breast cancer (0.4%, n=1). Of the 9 patients with occult neoplasms, 5 (2.0%) were identified from the 178 breast cancer patients, and 4 (1.6%) were detected in 65 healthy mutation carriers. During the median follow-up period of 36.7 months (interquartile range, 25.9-71.4), 1 (0.4%) BRCA1 PV carrier with no precursor lesions at RRSO developed primary peritoneal carcinomatosis after 30.1 months. CONCLUSION Women with HRR gene mutations PV/LPV who undergo RRSO are at a risk of detecting occult neoplasms, with a of 3.5%. Even in the absence of precursor lesions during RRSO, there was a cumulative risk of peritoneal carcinomatosis development, emphasizing the need for continued surveillance.
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Affiliation(s)
- Yeon Jee Lee
- Center for Gynecologic Cancer, Hospital, National Cancer Center, Goyang, Korea
- Department of Obstetrics and Gynecology, Myongji Hospital, Goyang, Korea
| | - Ji Hyun Kim
- Center for Gynecologic Cancer, Hospital, National Cancer Center, Goyang, Korea
| | - Youn Jee Kim
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
| | - Yoon Jung Chang
- Department of Family Medicine, Research Institute and Hospital, National Cancer Center, Goyang, Korea
| | - Sun-Young Kong
- Department of Laboratory Medicine and Genetic Counseling Clinic, Hospital, National Cancer Center, Goyang, Korea
| | - Chong Woo Yoo
- Center for Gynecologic Cancer and Department of Pathology, Research Institute and Hospital, National Cancer Center, Goyang, Korea
| | - Dong Ock Lee
- Center for Gynecologic Cancer, Hospital, National Cancer Center, Goyang, Korea
| | - Sang-Soo Seo
- Center for Gynecologic Cancer, Hospital, National Cancer Center, Goyang, Korea
| | - Sokbom Kang
- Center for Gynecologic Cancer, Hospital, National Cancer Center, Goyang, Korea
| | - Sang-Yoon Park
- Center for Gynecologic Cancer, Hospital, National Cancer Center, Goyang, Korea
| | - Myong Cheol Lim
- Center for Gynecologic Cancer, Hospital, National Cancer Center, Goyang, Korea
- Rare and Pediatric Cancer Branch and Immuno-Oncology Branch, Division of Rare and Refractory Cancer, Research Institute and Center for Clinical Trial, Hospital, National Cancer Center, Goyang, Korea
- Department of Cancer Control and Policy, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea.
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8
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Le Saux O, McNeish I, D'Incalci M, Narducci F, Ray-Coquard I. Controversies in the management of serous tubal intra-epithelial carcinoma lesions of the fallopian tube. Int J Gynecol Cancer 2025; 35:101667. [PMID: 39987717 DOI: 10.1016/j.ijgc.2025.101667] [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: 11/27/2024] [Revised: 01/23/2025] [Accepted: 01/24/2025] [Indexed: 02/25/2025] Open
Abstract
High-grade serous carcinoma is the most lethal gynecological malignancy. Although serous tubal intra-epithelial carcinoma is increasingly recognized as a precursor to high-grade serous carcinoma, its optimal management remains controversial. This review examines the controversies in serous tubal intra-epithelial carcinoma pathogenesis, diagnosis, management, and follow-up, highlighting the need for collaboration, standardized guidelines, and further research to improve patient outcomes.
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Affiliation(s)
- Olivia Le Saux
- Department of Medical Oncology, Center Léon Bérard, Lyon, France; Université Claude Bernard Lyon 1, Université de Lyon, Centre Léon Bérard, INSERM 1052-CNRS 5286, Cancer Research Center of Lyon, "Cancer Immune Surveillance and Therapeutic Targeting" Laboratory, Lyon, France.
| | - Iain McNeish
- Department of Surgery and Cancer, Imperial College London, London, United Kingdom
| | - Maurizio D'Incalci
- Department of Biomedical Sciences, Humanitas University, Milan, Italy; IRCCS Humanitas Research Hospital, Laboratory of Cancer Pharmacology, Rozzano, Milan, Italy
| | | | - Isabelle Ray-Coquard
- Department of Medical Oncology, Center Léon Bérard, Lyon, France; University Claude Bernard Lyon I Laboratoire RESHAPE U1290, Lyon, France
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9
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Bauer S, Oza A, Lheureux S. High-grade serous ovarian cancer-bridging the gap between epidemiology and prevention with biology. Int J Gynecol Cancer 2025; 35:101662. [PMID: 39923639 DOI: 10.1016/j.ijgc.2025.101662] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/11/2025] Open
Affiliation(s)
- Smadar Bauer
- Department of Medical Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada
| | - Amit Oza
- Department of Medical Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada
| | - Stephanie Lheureux
- Department of Medical Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada.
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10
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Wei YF, Ning L, Xu YL, Ma J, Li DR, Feng ZF, Liu FH, Li YZ, Xu HL, Li P, Yu YP, Huang DH, Li XY, Gao S, Lin CQ, Gong TT, Wu QJ, Lang JH. Worldwide patterns and trends in ovarian cancer incidence by histological subtype: a population-based analysis from 1988 to 2017. EClinicalMedicine 2025; 79:102983. [PMID: 39720606 PMCID: PMC11667631 DOI: 10.1016/j.eclinm.2024.102983] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2024] [Revised: 11/14/2024] [Accepted: 11/20/2024] [Indexed: 12/26/2024] Open
Abstract
BACKGROUND Ovarian cancer (OC) is a heterogeneous malignancy with multiple histological subtypes, showing global variability in incidence. Temporal changes in diagnostic criteria and risk factors might influence the incidence and distribution of OC and its subtypes. METHODS This study analyzed incidence patterns (2013-2017) and trends (1988-1992 to 2013-2017) of OC and its subtypes across 65 and 40 countries, respectively. Data were extracted from the Cancer Incidence in Five Continents (CI5 Ⅻ) and CI5plus databases (accessed in June 2024). Annual percent changes were computed to describe trends in age-standardized rates (ASRs) of OC and its subtypes. Proportions of ASR for each subtype relative to the ASR of OC for individual countries were calculated. FINDINGS The incidence of OC displayed marked disparities across regions and Human Development Index (HDI), with the highest ASRs in Eastern and Central Europe and very high HDI regions, and the lowest in Africa, Asia, and medium HDI regions. Despite stable trend in ASRs of OC globally, notable declines were observed in Europe, America, and Oceania, in contrast to increases in Asian countries like Japan and South Korea. Globally, serous carcinomas remained the most prevalent subtype. European countries exhibited a higher proportion of serous carcinomas, while Asian countries had a higher proportion of endometrioid and clear cell carcinomas. Although trends in subtypes also remained stable, ASRs increased over time for serous carcinomas and germ cell tumor in most countries, while mucinous carcinomas and adenocarcinoma NOS showed a decline. INTERPRETATION Variations in global patterns and trends in OC incidence and its subtypes might be influenced by genetic and reproductive factors. Consequently, region-specific prevention strategies and ongoing surveillance are essential to mitigate the burden of OC. FUNDING The National Key Research and Development Program of China (No.2022YFC2704205), the Natural Science Foundation of China (No.82073647, 82373674, and 82103914), Outstanding Scientific Fund of Shengjing Hospital, 345 Talent Project of Shengjing Hospital of China Medical University, the Max Planck - University of Helsinki Center from the Jane and Aatos Erkko Foundation (No.210046), the Max Planck Society (No.5714240218), the University of Helsinki (No.77204227), and the European Union (ERC Synergy, BIOSFER, 101071773).
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Affiliation(s)
- Yi-Fan Wei
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
- Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - Li Ning
- Gynecology Oncology, National Clinical Research Center for Cancer, National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yi-Lin Xu
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
- Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - Jing Ma
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Dong-Run Li
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
- Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - Zan-Fei Feng
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
- Department of Epidemiology, School of Public Health, China Medical University, Shenyang, China
| | - Fang-Hua Liu
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
- Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yi-Zi Li
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
- Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - He-Li Xu
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
- Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - Peng Li
- Max Planck Institute for Demographic Research, Rostock, Mecklenburg-Vorpommern, Germany
- Max Planck – University of Helsinki Center for Social Inequalities in Population Health, Rostock, Germany and Helsinki, Finland
| | - Yong-Pei Yu
- Institute of Advanced Clinical Medicine, Peking University, Beijing, China
| | - Dong-Hui Huang
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
- Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - Xiao-Ying Li
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
- Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - Song Gao
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Chun-Qing Lin
- National Clinical Research Center for Cancer, National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ting-Ting Gong
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Qi-Jun Wu
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
- Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
- NHC Key Laboratory of Advanced Reproductive Medicine and Fertility (China Medical University), National Health Commission, Shenyang, China
| | - Jing-He Lang
- Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetric and Gynaecological Diseases, State Key Laboratory of Common Mechanism Research for Major Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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11
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Yoon KH, Kim EK, Shin HC. Prognostic implications of ductal carcinoma in situ components in BRCA1/2-positive breast cancer: a retrospective cohort study. Ann Surg Treat Res 2024; 107:327-335. [PMID: 39669383 PMCID: PMC11634396 DOI: 10.4174/astr.2024.107.6.327] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Revised: 09/24/2024] [Accepted: 10/10/2024] [Indexed: 12/14/2024] Open
Abstract
Purpose Although the breast cancer susceptibility gene (BRCA)-associated invasive breast cancer is well studied, there are limited reports on ductal carcinoma in situ (DCIS) in patients with BRCA1/2 mutations. This study aims to evaluate the differential prognostic effect of DCIS in breast cancer patients with pathologic variants of BRCA1/2 genes. Methods Breast cancer patients who tested positive for BRCA1/2 mutations between August 2003 and January 2022 at a single tertiary referral center were retrospectively analyzed. Survival outcomes were compared between patients with both invasive ductal carcinoma (IDC) and DCIS (IDC-DCIS group, n = 121) and those with IDC alone (IDC group, n = 36). Results Of the 157 patients, 65 (41.4%) exhibited mutations in BRCA1, 90 (57.3%) in BRCA2, and 2 (1.3%) in both BRCA1/2. DCIS components were more frequently found in BRCA2 pathological variants (BRCA1, 46 [38.0%] vs. BRCA2, 76 [62.4%]; P = 0.030). No statistically significant difference was found in 10-year recurrence-free survival (IDC-DCIS, 89.3% vs. IDC, 83.6%; P = 0.989). Subgroup analysis indicated that the DCIS component correlated with improved survival outcomes in the BRCA1 subgroup (BRCA1 IDC-DCIS, 85.5% vs. BRCA1 IDC, 51.0%; P = 0.024). Conversely, in the BRCA2 subgroup, IDC-DCIS patients exhibited a worse prognosis (BRCA1 IDC-DCIS, 85.5% vs. BRCA2 IDC-DCIS, 65.8%; P = 0.045). Conclusion The presence of a DCIS component carries varied prognostic significance in BRCA1 and BRCA2 mutations. A tailored approach may be necessary when determining treatment options for breast cancer patients with BRCA1/2 mutations based on the presence of DCIS.
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Affiliation(s)
- Kyung-Hwak Yoon
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Eun-Kyu Kim
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Hee-Chul Shin
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
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MacArthur E, Stone R. Current Science and Practice of Surgical and Nonsurgical Opportunities for Ovarian Cancer Prevention. Clin Obstet Gynecol 2024; 67:676-686. [PMID: 39344701 DOI: 10.1097/grf.0000000000000900] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/01/2024]
Abstract
Due to improved understanding of ovarian cancer pathogenesis, we have an unprecedented chance to decrease the burden of disease by maximizing opportunities for prevention. Innovations in surgical options for prevention stem from the discovery that many cases directly or indirectly arise from the fallopian tube. Surgical prevention with salpingectomy alone decreases risk by ≥50%. Effective hormonal and nonhormonal chemopreventive agents are also available. Risk stratification is key to ensuring that options for prevention are appropriately matched to individual risk profile. This evidence-based review provides a critical appraisal of the translational health research endeavors supporting ovarian cancer prevention in clinical practice.
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Affiliation(s)
- Emily MacArthur
- Kelly Gynecologic Oncology Service, Johns Hopkins University, Baltimore, Maryland
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13
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Kim D, Ryu JM, Han SA, Kim Z, Kim SW. Pattern Anlysis of Risk-Reducing Strategies in Unaffected Korean BRCA1/2 Mutation Carriers. Curr Oncol 2024; 31:6767-6777. [PMID: 39590130 PMCID: PMC11592990 DOI: 10.3390/curroncol31110499] [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: 09/14/2024] [Revised: 10/23/2024] [Accepted: 10/28/2024] [Indexed: 11/28/2024] Open
Abstract
The lifetime risk of breast and ovarian cancer increases substantially for individuals with mutations in BRCA1/2. The evidence indicates that BRCA1/2 mutation carriers benefit from early cancer detection and prevention strategies. However, data on the patterns of risk-reducing interventions are lacking. This study investigated the patterns of surveillance and risk-reducing interventions among unaffected BRCA1/2 mutation carriers. A cohort of unaffected BRCA1/2 mutation carriers was identified from the Korean Hereditary Breast cAncer (KOHBRA) study database, and a telephone survey was conducted. The survey included questions on the incidence of new cancers, patterns of cancer (breast, ovarian, prostate, other) surveillance, chemoprevention, risk-reducing surgery, and reasons for participating in risk-reducing strategies. Between November 2016 and November 2020, 192 BRCA1/2 mutation carriers were contacted, of which 83 responded. After excluding 37 responders who refused to participate, 46 participants (15 males, 31 females) were included in the analysis. The mean ± SD follow-up time was 103 ± 17 months (median 107, range 68~154), and the mean ± SD age was 31 ± 8 years. Ten BRCA1/2 mutation carriers developed breast cancer, one developed ovarian cancer, and three developed other cancers. Six BRCA1/2 mutation carriers (19.4%) underwent annual breast cancer surveillance as recommended by guidelines, while none underwent ovarian or prostate cancer surveillance. Three carriers (9.7%) used chemoprevention for breast cancer. Risk-reducing salpingo-oophorectomy was performed on only one BRCA1/2 mutation carrier. The rates of breast/ovarian cancer surveillance, chemoprevention, and risk-reducing surgery were low among unaffected Korean BRCA1/2 mutation carriers. Given this cohort's relatively high risk of developing breast cancer, strategies to encourage active participation in risk reduction are needed.
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Affiliation(s)
- Dabin Kim
- Department of Surgery, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon 14584, Republic of Korea;
| | - Jai Min Ryu
- Division of Breast Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea;
| | - Sang-Ah Han
- Department of Surgery, Kyung Hee University Hospital at Gangdong, Seoul 05278, Republic of Korea;
| | - Zisun Kim
- Department of Surgery, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon 14584, Republic of Korea;
| | - Sung-Won Kim
- Department of Surgery, Daerim St. Mary’s Hospital, Seoul 07442, Republic of Korea
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14
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Choi YJ, Park Y, Park B, Chae H, Jung SY, Ryu KH, Lim MC, Park SJ, Chang YJ, Kong SY. Impact of graphical display on the intention to undergo risk-reducing salpingo-oophorectomy and mastectomy in individuals positive for BRCA pathogenic variant. Sci Rep 2024; 14:24281. [PMID: 39414838 PMCID: PMC11484698 DOI: 10.1038/s41598-024-73929-0] [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: 05/17/2024] [Accepted: 09/23/2024] [Indexed: 10/18/2024] Open
Abstract
The BRCA1/2 pathogenic variant (PV) increases the risk of breast and ovarian cancer; thus, risk-reducing salpingo-oophorectomy (RRSO) and mastectomy (RRM) are recommended. We evaluated the effects of the graphical display of cancer risk compared with those of numerical presentation on the decision-making for risk-reducing (RR) surgery. A total of 471 women representing the Korean population were recruited. The lifetime risk of breast/ovarian cancer were given numerically followed by graphically in hypothetical BRCA1/2 PV-positive cases. Subsequently, the study participants were asked for their willingness to undergo RRSO/RRM. When the ovarian cancer risk was shown as 44.0%, the percentage of study participants who chose RRSO was 41.0% after numerical presentation versus 39.9% after graphical display, of which the difference was not significant. When the breast cancer risk was presented as 72.0%, 30.4% of the participants opted for RRM under numerical presentation, whereas this increased to 38.6% under graphical display, of which the difference was significant (p < 0.0075). The average levels of the cancer risk which study participants consider RR surgery were 57.1% for ovarian cancer and 60.6% for breast cancer. This suggests that the impacts of different formats of risk communication on decision about RRSO or RRM may be different by the absolute levels of ovarian or breast cancer.
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Affiliation(s)
- Yoon-Jung Choi
- Department of Cancer Control and Population Health, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Republic of Korea
- National Cancer Control Institute, National Cancer Center, Goyang, Republic of Korea
- Center for Cancer Prevention & Detection, National Cancer Center Hospital, Goyang, Republic of Korea
| | - Younju Park
- National Cancer Control Institute, National Cancer Center, Goyang, Republic of Korea
| | - Boyoung Park
- Department of Preventive Medicine, Hanyang University College of Medicine, Seoul, Republic of Korea
| | - Heejung Chae
- Center for Breast Cancer, National Cancer Center Hospital, Goyang, Republic of Korea
| | - So-Youn Jung
- Center for Breast Cancer, National Cancer Center Hospital, Goyang, Republic of Korea
| | - Kum Hei Ryu
- Center for Cancer Prevention & Detection, National Cancer Center Hospital, Goyang, Republic of Korea
| | - Myong Cheol Lim
- Center for Gynecologic Cancer, National Cancer Center Hospital, Goyang, Republic of Korea
| | - Soo Jin Park
- Department of Surgery, Wonkwang University Sanbon Hospital, Gunpo, Republic of Korea
| | - Yoon Jung Chang
- National Cancer Survivorship Center, National Cancer Control Institute, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 10408, Republic of Korea.
- Department of Cancer AI & Digital Health, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Republic of Korea.
| | - Sun-Young Kong
- Targeted Therapy Branch, Research Institute, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 10408, Republic of Korea.
- Department of Laboratory Medicine, Hospital, National Cancer Center, Goyang, Republic of Korea.
- Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Republic of Korea.
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Heppell C, Malka S, Moosajee M. Incidental finding of a BRCA2 variant following whole genome sequencing to molecularly diagnose bilateral congenital cataracts. BMJ Case Rep 2024; 17:e260755. [PMID: 39395831 PMCID: PMC11474931 DOI: 10.1136/bcr-2024-260755] [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: 04/27/2024] [Accepted: 09/30/2024] [Indexed: 10/14/2024] Open
Abstract
A male patient in his 20s with a history of bilateral congenital cataracts and nystagmus presented to the genetic eye disease clinic at Moorfields Eye Hospital to enquire about genetic testing for family decision-making and access to preimplantation genetic testing. He had a history of lensectomy with best-corrected visual acuities of logMAR 0.60 and 1.00 in the right and left eye. Whole genome sequencing (WGS) was conducted, which included targeted analysis of a panel of 115 lens-related genes and incidental findings, for which patients are unable to opt-out. Genetic testing identified the causative variant c.134T>C (p.Leu45Pro) in the CRYGC gene. A pathogenic variant in BRCA2 was also identified as a secondary finding. This was unexpected given the absence of a strong family history of breast or ovarian cancer. This case illustrates the importance of genetic counselling and informing patients about the implications of incidental findings that arise from WGS.
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Affiliation(s)
- Cara Heppell
- Genetics Service, Moorfields Eye Hospital NHS Foundation Trust, London, UK
| | - Samantha Malka
- Genetics Service, Moorfields Eye Hospital NHS Foundation Trust, London, UK
| | - Mariya Moosajee
- Genetics Service, Moorfields Eye Hospital NHS Foundation Trust, London, UK
- Development, Ageing and Disease, UCL Institute of Ophthalmology, London, UK
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16
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Polan RM, Ali-Fehmi R, Grace AK, Mattei LH, Tanner EJ, Morris RT. Occult residual ovarian tissue at the time of minimally invasive risk reducing surgery in women with BRCA mutations. Gynecol Oncol 2024; 189:37-40. [PMID: 39003959 DOI: 10.1016/j.ygyno.2024.07.005] [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: 06/17/2024] [Accepted: 07/08/2024] [Indexed: 07/16/2024]
Abstract
OBJECTIVE To describe extension of ovarian tissue beyond visible and National Comprehensive Cancer Network recommended margins among patients with BRCA mutations undergoing minimally invasive risk-reducing salpingo-oophorectomy. METHODS A prospective study of patients with BRCA mutations who underwent minimally invasive risk-reducing bilateral salpingo-oophorectomy was conducted. Patient enrollment occurred between October 2021 and 2023. Tissue specimens were analyzed according to the Sectioning and Extensively Examining the Fimbriated End protocol. RESULTS Twenty women with BRCA mutations were prospectively enrolled. All patients underwent minimally invasive surgery with 70% undergoing concurrent hysterectomy (n = 14). Approximately half of these procedures were performed with robotic assistance (n = 9, 45%). One patient was admitted overnight (5%); the other nineteen were discharged on the day of surgery (95%). One patient experienced a major complication and required readmission (5%). Extension of ovarian tissue beyond the visible ovary was noted on pathologic examination of six specimens (30%). In one patient this was observed on the left (17%), in three on the right (50%), and in two bilateral extension (33%) was noted. The distance ovarian stroma extended microscopically beyond the visible ovary was between 2 and 14 mm, with a median of 5 mm. Among patients with microscopic extension of ovarian tissue, the majority (n = 5, 83%) had a BRCA2 mutation. CONCLUSION In women with BRCA mutations undergoing risk-reducing minimally invasive surgery, approximately one third had microscopic extension of ovarian stroma beyond the visible ovary. Current guidelines which recommend resection of at least 20 mm of tissue beyond the visible ovary are likely adequate in this population.
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Affiliation(s)
- Rosa M Polan
- Department of Gynecologic Oncology, Barbara Ann Karmanos Cancer Institute, Detroit, MI, USA.
| | - Rouba Ali-Fehmi
- Department of Pathology, University of Michigan, Ann Arbor, MI, USA
| | - Anne K Grace
- Department of Gynecologic Oncology, Northwestern Prentice Women's Hospital, Chicago, IL, USA
| | - Larissa H Mattei
- Department of Gynecologic Oncology, Barbara Ann Karmanos Cancer Institute, Detroit, MI, USA
| | - Edward J Tanner
- Department of Gynecology and Obstetrics, Johns Hopkins University, Baltimore, MD, USA
| | - Robert T Morris
- Department of Gynecologic Oncology, Barbara Ann Karmanos Cancer Institute, Detroit, MI, USA
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Timme K, González-Alvarez ME, Keating AF. Pre-pubertal obesity compromises ovarian oxidative stress, DNA repair and chemical biotransformation. Toxicol Appl Pharmacol 2024; 489:116981. [PMID: 38838792 DOI: 10.1016/j.taap.2024.116981] [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: 03/11/2024] [Revised: 05/22/2024] [Accepted: 05/25/2024] [Indexed: 06/07/2024]
Abstract
Obesity in adult females impairs fertility by altering oxidative stress, DNA repair and chemical biotransformation. Whether prepubertal obesity results in similar ovarian impacts is under-explored. The objective of this study was to induce obesity in prepubertal female mice and assess puberty onset, follicle number, and abundance of oxidative stress, DNA repair and chemical biotransformation proteins basally and in response to 7,12-dimethylbenz(a)anthracene (DMBA) exposure. DMBA is a polycyclic aromatic hydrocarbon that has been shown to be ovotoxic. Lactating dams (C57BL6J) were fed either a normal rodent containing 3.5% kCal from fat (lean), or a high fat diet comprised of 60% kCal from fat, and 9% kCal from sucrose. The offspring were weaned onto the diet of their dam and exposed at postnatal day 35 to either corn oil or DMBA (1 mg/kg) for 7 d via intraperitoneal injection. Mice on the HFD had reduced (P < 0.05) age at puberty onset as measured by vaginal opening but DMBA did not impact puberty onset. Heart, spleen, kidney, uterus and ovary weight were increased (P < 0.05) by obesity and liver weight was increased (P < 0.05) by DMBA exposure in obese mice. Follicle number was largely unaffected by obesity or DMBA exposure, with the exception of primary follicle number, which were higher (P < 0.05) in lean DMBA exposed and obese control relative to lean control mice. There were also greater numbers (P < 0.05) of corpora lutea in obese relative to lean mice. In lean mice, DMBA exposure reduced (P < 0.05) the level of CYP2E1, EPHX1, GSTP1, BRCA1, and CAT but this DMBA-induced reduction was absent in obese mice. Basally, obesity reduced (P < 0.05) the abundance of CYP2E1, EPHX1, GSTP1, BRCA1, SOD1 and CAT. There was greater (P < 0.05) fibrotic staining in obese DMBA-exposed ovaries and PPP2CA was decreased (P < 0.05) in growing follicles by both obesity and DMBA exposure. Thus, prepubertal obesity alters the capacity of the ovary to respond to DNA damage, ovotoxicant exposure and oxidative stress.
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Affiliation(s)
- Kelsey Timme
- Department of Animal Science, Iowa State University, Ames, IA, USA
| | | | - Aileen F Keating
- Department of Animal Science, Iowa State University, Ames, IA, 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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19
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Suzuki R, Tan X, Szymanska KJ, Kubikova N, Perez CA, Wells D, Oktay KH. The role of declining ataxia-telangiectasia-mutated (ATM) function in oocyte aging. Cell Death Discov 2024; 10:302. [PMID: 38914566 PMCID: PMC11196715 DOI: 10.1038/s41420-024-02041-z] [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: 03/29/2024] [Revised: 05/04/2024] [Accepted: 05/22/2024] [Indexed: 06/26/2024] Open
Abstract
Despite the advances in the understanding of reproductive physiology, the mechanisms underlying ovarian aging are still not deciphered. Recent research found an association between impaired ATM-mediated DNA double-strand break (DSB) repair mechanisms and oocyte aging. However, direct evidence connecting ATM-mediated pathway function decline and impaired oocyte quality is lacking. The objective of this study was to determine the role of ATM-mediated DNA DSB repair in the maintenance of oocyte quality in a mouse oocyte knockdown model. Gene interference, in vitro culture, parthenogenesis coupled with genotoxicity assay approaches, as well as molecular cytogenetic analyses based upon next-generation sequencing, were used to test the hypothesis that intact ATM function is critical in the maintenance of oocyte quality. We found that ATM knockdown impaired oocyte quality, resulting in poor embryo development. ATM knockdown significantly lowered or blocked the progression of meiosis in vitro, as well as retarding and reducing embryo cleavage after parthenogenesis. After ATM knockdown, all embryos were of poor quality, and none reached the blastocyst stage. ATM knockdown was also associated with an increased aneuploidy rate compared to controls. Finally, ATM knockdown increased the sensitivity of the oocytes to a genotoxic active metabolite of cyclophosphamide, with increased formation of DNA DSBs, reduced survival, and earlier apoptotic death compared to controls. These findings suggest a key role for ATM in maintaining oocyte quality and resistance to genotoxic stress, and that the previously observed age-induced decline in oocyte ATM function may be a prime factor contributing to oocyte aging.
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Affiliation(s)
- Reiko Suzuki
- Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, USA
| | - Xiujuan Tan
- Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, USA
| | - Katarzyna J Szymanska
- Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, USA
| | - Nada Kubikova
- Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford, United Kingdom
| | - Columba Avila Perez
- Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford, United Kingdom
| | - Dagan Wells
- Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford, United Kingdom
- Juno Genetics, Oxford, United Kingdom
| | - Kutluk H Oktay
- Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, USA.
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20
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Chalker C, Chun B, Sokolova AO. Germline and somatic mutations in prostate cancer: Implications for treatment. Curr Probl Cancer 2024; 50:101101. [PMID: 38718711 DOI: 10.1016/j.currproblcancer.2024.101101] [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: 12/21/2023] [Revised: 04/15/2024] [Accepted: 04/25/2024] [Indexed: 06/16/2024]
Abstract
Genetic testing is an integral part of the workup of metastatic prostate cancer, in part, because the results can have a profound impact on the subsequent management of this disease. There are now several Food & Drug Administration (FDA) approved therapeutics available for patients with prostate cancer and certain genetic abnormalities - most notably, mutations in DNA damage repair (DDR) pathways such mismatch repair (MMR) and homologous recombination repair (HRR). In this review of the current literature, we discuss the indications for somatic and germline testing, the genetic changes of particular clinical relevance, the associated therapeutic options, and the clinical data supporting their use. We also highlight select trials-in-progress and future directions for the field.
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Affiliation(s)
- Cameron Chalker
- Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR 97239.
| | - Brie Chun
- Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR 97239
| | - Alexandra O Sokolova
- Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR 97239
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21
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Bowen CM, Demarest K, Vilar E, Shah PD. Novel Cancer Prevention Strategies in Individuals With Hereditary Cancer Syndromes: Focus on BRCA1, BRCA2, and Lynch Syndrome. Am Soc Clin Oncol Educ Book 2024; 44:e433576. [PMID: 38913968 DOI: 10.1200/edbk_433576] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/26/2024]
Abstract
Germline pathogenic variants (PVs) in the BRCA1 and BRCA2 genes confer elevated risks of breast, ovarian, and other cancers. Lynch syndrome (LS) is associated with increased risks of multiple cancer types including colorectal and uterine cancers. Current cancer risk mitigation strategies have focused on pharmacologic risk reduction, enhanced surveillance, and preventive surgeries. While these approaches can be effective, they stand to be improved on because of either limited efficacy or undesirable impact on quality of life. The current review summarizes ongoing investigational efforts in cancer risk prevention strategies for patients with germline PVs in BRCA1, BRCA2, or LS-associated genes. These efforts span radiation, surgery, and pharmacology including vaccine strategies. Understanding the molecular events involved in the premalignant to malignant transformation in high-risk individuals may ultimately contribute significantly to novel prevention strategies.
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Affiliation(s)
- Charles M Bowen
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX
| | | | - Eduardo Vilar
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Payal D Shah
- Perelman Center for Advanced Medicine, Abramson Cancer Center, Philadelphia, PA
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22
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Wilke RN, Bednar EM, Pirzadeh-Miller S, Lahiri S, Scarinci IC, Leath Iii CA, Frey MK, Lu KH, Rauh-Hain JA. Cascade genetic testing: an underutilized pathway to equitable cancer care? Fam Cancer 2024; 23:141-145. [PMID: 38748383 PMCID: PMC11751770 DOI: 10.1007/s10689-024-00367-2] [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: 12/01/2023] [Accepted: 02/14/2024] [Indexed: 06/06/2024]
Abstract
The Precision Medicine Initiative was launched upon the potential of genomic information to tailor medical care. Cascade genetic testing represents a powerful application of precision medicine and involves the process of familial diffusion or the "cascade" of genomic risk information. When an individual (proband) is found to carry a cancer-associated germline pathogenic mutation, the information should be cascaded or shared with at-risk relatives. First degree relatives have a 50% likelihood of carrying the same cancer-associated mutation. This process of cascade testing offers at-risk relatives the opportunity for genetic testing and, for those who also carry the cancer-associated mutation, genetically targeted primary disease prevention through intensive cancer surveillance, chemoprevention and risk-reducing surgery, reducing morbidity and preventing mortality. Cascade testing has been designated by the Centers for Disease Control and Prevention as a Tier 1 genomic application for hereditary breast and ovarian cancer. In this manuscript we describe a cascade genetic testing and in particular focus on its potential to provide necessary care to medically underserved and vulnerable populations.
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Affiliation(s)
- Roni Nitecki Wilke
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, 1155 Herman Pressler Drive, 77030-1362, Houston, TX, USA.
| | - Erica M Bednar
- Cancer Prevention and Control Platform, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Sara Pirzadeh-Miller
- Cancer Genetics, The University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Sayoni Lahiri
- Cancer Genetics, The University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Isabel C Scarinci
- Division of Preventive Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Charles A Leath Iii
- O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Melissa K Frey
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Weill Cornell Medical College, New York, NY, USA
| | - Karen H Lu
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, 1155 Herman Pressler Drive, 77030-1362, Houston, TX, USA
| | - J Alejandro Rauh-Hain
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, 1155 Herman Pressler Drive, 77030-1362, Houston, TX, USA
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23
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Somasegar S, Reddy RA, Chow S, Dorigo O, Renz M, Karam A. Trends in ovarian, fallopian tube, and primary peritoneal cancer incidence, mortality, and survival: A 15-year population-based analysis. Gynecol Oncol 2024; 184:190-197. [PMID: 38330833 DOI: 10.1016/j.ygyno.2024.01.034] [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: 10/04/2023] [Revised: 01/13/2024] [Accepted: 01/22/2024] [Indexed: 02/10/2024]
Abstract
OBJECTIVE To characterize trends in ovarian, fallopian tube, and primary peritoneal cancer incidence and incidence-based mortality based on histology and site of origin. METHODS We obtained age-adjusted incidence and incidence-based mortality for patients with ovarian, fallopian tube, and primary peritoneal cancer from 2000 to 2019 from the US SEER 17 database. Joinpoint 4.9.1.0 was used to characterize log-linear time trends. RESULTS The incidence and incidence-based mortality of all cancers trended down during the study period. The incidence of epithelial cancers decreased from 2004 to 2019 (AAPC -1.2%, p < 0.001), including that of high-grade (2006-2019: APC -1.2%, p < 0.05) and low-grade (2003-2019: APC -2.4%, p < 0.05) epithelial cancers. There was no change in incidence or incidence-based mortality for ovarian stromal and germ cell cancers. CONCLUSION There has been a decrease in the incidence and incidence-based mortality of ovarian, fallopian tube, and primary peritoneal cancer, primarily due to reductions in advanced stage epithelial cancers originating in the ovary, fallopian tube, or peritoneum.
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Affiliation(s)
- Sahana Somasegar
- Stanford University School of Medicine, Department of Obstetrics & Gynecology, Division of Gynecologic Oncology, Palo Alto, CA, United States of America.
| | - Ravali A Reddy
- Stanford University School of Medicine, Department of Obstetrics & Gynecology, Division of Gynecologic Oncology, Palo Alto, CA, United States of America
| | - Stephanie Chow
- Stanford University School of Medicine, Department of Obstetrics & Gynecology, Division of Gynecologic Oncology, Palo Alto, CA, United States of America
| | - Oliver Dorigo
- Stanford University School of Medicine, Department of Obstetrics & Gynecology, Division of Gynecologic Oncology, Palo Alto, CA, United States of America
| | - Malte Renz
- Stanford University School of Medicine, Department of Obstetrics & Gynecology, Division of Gynecologic Oncology, Palo Alto, CA, United States of America
| | - Amer Karam
- Stanford University School of Medicine, Department of Obstetrics & Gynecology, Division of Gynecologic Oncology, Palo Alto, CA, United States of America
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24
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Martin FJ, Saffie IM, Hurtado MA, Avila-Jaque D, Lagos RA, Selman CA, Huserman JZ, Castillo VA, Chahuán BJ. Variants in BRCA1/2 in a hospital-based cohort in Chile and national literature review. Ecancermedicalscience 2024; 18:1683. [PMID: 38566764 PMCID: PMC10984842 DOI: 10.3332/ecancer.2024.1683] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2023] [Indexed: 04/04/2024] Open
Abstract
Purpose The aim was to assess the diagnostic yield of next generation sequencing (NGS) multi-gene panels for breast and ovarian cancer in a high-complexity cancer centre in Chile. Additionally, our goal was to broaden the genotypic spectrum of BRCA variants already identified in Chilean families. Methods Retrospective analysis was conducted on the genetic test results of 722 individuals from Fundación Arturo López Pérez's genetic counselling unit between 2016 and 2021. A comprehensive literature review encompassing articles analysing the frequency of germinal pathogenic variants in BRCA1/2 within the Chilean population was undertaken. Results 23.5% of the panels had positive results, with 60% due to pathogenic variants in the BRCA1/2 genes. Seven previously unreported variants in BRCA1 from Chilean studies were identified.One or more variants of uncertain significance were detected in 31% of the results, and 11.5% of the families in this cohort presented copy number variants (CNVs) in BRCA1/2.8 studies analysed the frequency of pathogenic variants in BRCA1/2 in the Chilean population between 2006 and 2023, with a frequency between 7.1% and 17.1%.51 BRCA1 variants in 149 families have been reported in Chile and 38 BRCA2 variants in 132 families. Nine founder pathogenic variants identified by one study were present in 51.9% of the total Chilean families reported. Conclusion Our findings advocate for the integration of NGS multi-gene panel testing as a primary strategy within our population. This approach allows for the comprehensive assessment of single nucleotide variants and CNVs in BRCA1/2, alongside other high and moderately penetrant genes associated with breast and ovarian cancer.
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Affiliation(s)
- Fernanda J Martin
- Unidad Asesoramiento Genético Oncológico, Fundación Arturo López Pérez, Santiago 7500921, Chile
- https://orcid.org/0000-0002-7167-8850
| | - Isabel M Saffie
- Cirugía de mama, Fundación Arturo López Pérez, Santiago 7500921, Chile
- https://orcid.org/0000-0002-4723-5750
| | - Mabel A Hurtado
- Unidad Asesoramiento Genético Oncológico, Fundación Arturo López Pérez, Santiago 7500921, Chile
- Cirugía de mama, Fundación Arturo López Pérez, Santiago 7500921, Chile
| | - Diana Avila-Jaque
- Sección de Genética, Hospital San Juan de Dios, Santiago 8350488, Chile
- https://orcid.org/0009-0002-7787-6847
| | - Rodrigo A Lagos
- Unidad estadística, Fundación Arturo López Pérez, Santiago 7500921, Chile
- https://orcid.org/0000-0002-5806-6227
| | - Carolina A Selman
- Subdirección Unidades Diagnósticas, Fundación Arturo López Pérez, Santiago 7500921, Chile
| | - Jonathan Z Huserman
- Departamento Genética, Hospital Base San José Osorno, Osorno 5311523, Chile
- https://orcid.org/0000-0002-9355-3282
| | - Valentina A Castillo
- Departamento Genética, Hospital Clínico Universidad de Chile, Santiago 8380453, Chile
- Departamento Genética, Hospital Dr. Sótero del Río, Santiago 8150000, Chile
| | - Badir J Chahuán
- Unidad Asesoramiento Genético Oncológico, Fundación Arturo López Pérez, Santiago 7500921, Chile
- Cirugía de mama, Fundación Arturo López Pérez, Santiago 7500921, Chile
- https://orcid.org/0000-0003-3133-6706
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25
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Abe A, Nomura H, Fusegi A, Yunokawa M, Ueki A, Habano E, Arakawa H, Kaneko K, Minoura Y, Inari H, Ueno T, Kanao H. Risk-reducing decisions regarding germline BRCA pathogenic variant: focusing on the timing of genetic testing and RRSO. J Med Genet 2024; 61:392-398. [PMID: 38124001 PMCID: PMC10982634 DOI: 10.1136/jmg-2023-109549] [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: 07/31/2023] [Accepted: 11/21/2023] [Indexed: 12/23/2023]
Abstract
BACKGROUND In Japan, the public insurance policy was revised in 2020 to cover hereditary breast and ovarian cancer (HBOC), including genetic testing and surveillance, for patients with breast cancer (BC). Consequently, the demand for risk-reducing salpingo-oophorectomy (RRSO) has increased. This study aimed to clarify the changes in the demand and timing of genetic testing and RRSO associated with public insurance coverage for HBOC in Japan. METHODS This retrospective analysis included 350 women with germline BRCA (gBRCA) pathogenic variants (PVs) who had visited gynaecologists; they received gBRCA genetic testing at 45.1±10.6 (20-74) years. The use of medical testing and preventive treatment was compared between the preinsurance and postinsurance groups using Mann-Whitney U and Fisher's exact tests. RESULTS The findings indicate that RRSO rates doubled from 31.4% to 62.6% among patients with gBRCA-PV. The implementation rate was 32.4% among unaffected carriers and 70.3% among BC-affected patients. Younger patients received genetic testing with significantly shorter intervals between BC diagnosis and genetic testing and between genetic testing and RRSO. CONCLUSION Overall, the insurance coverage for HBOC patients with BC has increased the frequency of RRSO in Japan. However, a comparison between the number of probands and family members indicated that the diagnosis among family members is inadequate. The inequality in the use of genetic services by socioeconomic groups is an issue of further concern.
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Affiliation(s)
- Akiko Abe
- Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Hidetaka Nomura
- Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Atsushi Fusegi
- Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Mayu Yunokawa
- Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Arisa Ueki
- Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Eri Habano
- Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Hiromi Arakawa
- Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Keika Kaneko
- Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yuko Minoura
- Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Hitoshi Inari
- Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Takayuki Ueno
- Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Hiroyuki Kanao
- Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
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Meshkani Z, Moradi N, Aboutorabi A, Farabi H, Moini N. A cost-benefit analysis of genetic screening test for breast cancer in Iran. BMC Cancer 2024; 24:279. [PMID: 38429685 PMCID: PMC10905849 DOI: 10.1186/s12885-024-12003-4] [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: 02/17/2023] [Accepted: 02/14/2024] [Indexed: 03/03/2024] Open
Abstract
BACKGROUND This study aimed to evaluate the implementation of the population- and family history (FH) -based screening for BReast CAncer (BRCA) in Iran, a country where less than 10% of breast cancer cases are attributable to a gene mutation. METHODS This was an economic evaluation study. The Benefit-Cost Ratio (BCR) for genetic screening test strategies in Iranian women older than 30 was calculated. To this end, the monetary value of the test was estimated using the willingness-to-pay (WTP) approach using the contingent valuation method (CVM) by payment card. From a healthcare perspective, direct medical and non-medical costs were considered and a decision model for the strategies was developed to simulate the costs. A one-way sensitivity analysis assessed the robustness of the analysis. The data were analyzed using Excel 2010. RESULTS 660 women were included for estimating WTP and 2,176,919 women were considered in the costing model. The cost per genetic screening test for population- and FH-based strategies was $167 and $8, respectively. The monetary value of a genetic screening test was $20 and it was $27 for women with a family history or gene mutation in breast cancer. The BCR for population-based and FH-based screening strategies was 0.12 and 3.37, respectively. Sensitivity analyses confirmed the robustness of the results. CONCLUSIONS This study recommends the implementation of a FH-based strategy instead of a population-based genetic screening strategy in Iran, although a cascade genetic screening test strategy should be evaluated in future studies.
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Affiliation(s)
- Zahra Meshkani
- Department of Health Economics, School of Health Management and Information Sciences, Iran University of Medical Sciences, Tehran, Iran.
- Health Management and Economics Research Center, Iran University of Medical Sciences, 13833-19967, Tehran, Iran.
| | - Najmeh Moradi
- Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK
| | - Ali Aboutorabi
- Department of Health Economics, School of Health Management and Information Sciences, Iran University of Medical Sciences, Tehran, Iran
| | - Hiro Farabi
- Barts and The London Pragmatic Clinical Trial Unit, Centre for Evaluation and Methods, Wolfson Institute of Population Health, Queen Mary University of London, London, UK
| | - Nazi Moini
- Breast Cancer Research Centre, Motamed Cancer Institute, ACECR, Tehran, Iran
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Tantray J, Patel A, Prajapati BG, Kosey S, Bhattacharya S. The Use of Lipid-based Nanocarriers to Improve Ovarian Cancer Treatment: An Overview of Recent Developments. Curr Pharm Biotechnol 2024; 25:2200-2217. [PMID: 38357950 DOI: 10.2174/0113892010279572240126052844] [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: 11/14/2023] [Revised: 01/08/2024] [Accepted: 01/16/2024] [Indexed: 02/16/2024]
Abstract
Ovarian cancer poses a formidable health challenge for women globally, necessitating innovative therapeutic approaches. This review provides a succinct summary of the current research status on lipid-based nanocarriers in the context of ovarian cancer treatment. Lipid-based nanocarriers, including liposomes, solid lipid nanoparticles (SLNs), and nanostructured lipid carriers (NLCs), offer a promising solution for delivering anticancer drugs with enhanced therapeutic effectiveness and reduced adverse effects. Their versatility in transporting both hydrophobic and hydrophilic medications makes them well-suited for a diverse range of anticancer drugs. Active targeting techniques like ligand-conjugation and surface modifications have been used to reduce off-target effects and achieve tumour-specific medication delivery. The study explores formulation techniques and adjustments meant to enhance drug stability and encapsulation in these nanocarriers. Encouraging results from clinical trials and preclinical investigations underscore the promise of lipid-based nanocarriers in ovarian cancer treatment, providing optimism for improved patient outcomes. Notwithstanding these advancements, challenges related to clearance, long-term stability, and scalable manufacturing persist. Successfully translating lipidbased nanocarriers into clinical practice requires addressing these hurdles. To sum up, lipidbased nanocarriers are a viable strategy to improve the effectiveness of therapy for ovarian cancer. With their more focused medication administration and lower systemic toxicity, they may completely change the way ovarian cancer is treated and increase patient survival rates. Lipidbased nanocarriers need to be further researched and developed to become a therapeutically viable treatment for ovarian cancer.
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Affiliation(s)
- Junaid Tantray
- Department of Pharmacology, NIMS Institute of Pharmacy, NIMS University, Rajasthan, India
| | - Akhilesh Patel
- Department of Pharmacology, NIMS Institute of Pharmacy, NIMS University, Rajasthan, India
| | - Bhupendra G Prajapati
- Department of Pharmaceutics and Pharmaceutical Technology, Shree S.K. Patel College of Pharmaceutical Education & Research, Ganpat University, Gujarat, India
| | - Sourabh Kosey
- Department of Pharmacy Practice, ISF College of Pharmacy, Punjab, India
| | - Sankha Bhattacharya
- School of Pharmacy & Technology, Management, SVKM'S NMIMS Deemed-to-be University, Shirpur, Maharashtra, 425405, India
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Liu T, Yu J, Gao Y, Ma X, Jiang S, Gu Y, Ming WK. Prophylactic Interventions for Hereditary Breast and Ovarian Cancer Risks and Mortality in BRCA1/2 Carriers. Cancers (Basel) 2023; 16:103. [PMID: 38201529 PMCID: PMC10778044 DOI: 10.3390/cancers16010103] [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: 11/13/2023] [Revised: 12/16/2023] [Accepted: 12/21/2023] [Indexed: 01/12/2024] Open
Abstract
BACKGROUND Hereditary breast and ovarian cancers (HBOCs) pose significant health risks worldwide and are mitigated by prophylactic interventions. However, a meta-analysis of their efficacy and the impact of different genetic variants on their effectiveness is lacking. METHODS A systematic review and meta-analysis were conducted, adhering to Cochrane guidelines. The review encompassed studies that involved prophylactic interventions for healthy women with BRCA variants, focusing on cancer incidence and mortality outcomes. The Newcastle-Ottawa Scale was used for risk of bias assessment. We pooled the extracted outcomes using random effects models and conducted subgroup analyses stratified by intervention, variant, and cancer types. RESULTS A total of 21 studies met the inclusion criteria. The meta-analysis revealed that prophylactic interventions significantly reduced cancer risk and mortality. The subgroup analysis showed a greater protective effect for BRCA2 than BRCA1 variant carriers. Risk-reducing surgeries (RRS) were more effective than chemoprevention, with RRS notably reducing cancer risk by 56% compared to 39% for chemoprevention. Prophylactic oophorectomy significantly reduced HBOC risks, while the effect of prophylactic mastectomy and chemoprevention on mortality was less conclusive. CONCLUSIONS Prophylactic interventions significantly reduce the risk of HBOC and associated mortality. This comprehensive analysis provides insights for future economic evaluations and clinical decision-making in HBOC interventions.
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Affiliation(s)
- Taoran Liu
- Department of Infectious Diseases and Public Health, City University of Hong Kong, Hong Kong 999077, China
| | - Jing Yu
- Department of Infectious Diseases and Public Health, City University of Hong Kong, Hong Kong 999077, China
| | - Yangyang Gao
- Department of Infectious Diseases and Public Health, City University of Hong Kong, Hong Kong 999077, China
| | - Xinyang Ma
- Department of Infectious Diseases and Public Health, City University of Hong Kong, Hong Kong 999077, China
| | - Shan Jiang
- Macquarie University Centre for the Health Economy, Macquarie Business School and Australian Institute of Health Innovation, Macquarie University, Sydney, NSW 2109, Australia
| | - Yuanyuan Gu
- Macquarie University Centre for the Health Economy, Macquarie Business School and Australian Institute of Health Innovation, Macquarie University, Sydney, NSW 2109, Australia
| | - Wai-kit Ming
- Department of Infectious Diseases and Public Health, City University of Hong Kong, Hong Kong 999077, China
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Zattarin E, Taglialatela I, Lobefaro R, Leporati R, Fucà G, Ligorio F, Sposetti C, Provenzano L, Azzollini J, Vingiani A, Ferraris C, Martelli G, Manoukian S, Pruneri G, de Braud F, Vernieri C. Breast cancers arising in subjects with germline BRCA1 or BRCA2 mutations: Different biological and clinical entities with potentially diverse therapeutic opportunities. Crit Rev Oncol Hematol 2023; 190:104109. [PMID: 37643668 DOI: 10.1016/j.critrevonc.2023.104109] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Revised: 08/11/2023] [Accepted: 08/23/2023] [Indexed: 08/31/2023] Open
Abstract
Breast cancers (BCs) arising in carriers of germline BRCA1 and BRCA2 pathogenic variants (PVs) have long been considered as indistinguishable biological and clinical entities. However, the loss of function of BRCA1 or BRCA2 proteins has different consequences in terms of tumor cell reliance on estrogen receptor signaling and tumor microenvironment composition. Here, we review accumulating preclinical and clinical data indicating that BRCA1 or BRCA2 inactivation may differentially affect BC sensitivity to standard systemic therapies. Based on a different crosstalk between BRCA1 or BRCA2 and the ER pathway, BRCA2-mutated Hormone Receptor-positive, HER2-negative advanced BC may be less sensitive to endocrine therapy (ET) plus CDK 4/6 inhibitors (CDK 4/6i), whereas BRCA2-mutated triple-negative breast cancer (TNBC) may be especially sensitive to immune checkpoint inhibitors. If validated in future prospective studies, these data may have relevant clinical implications, thus establishing different treatment paths in patients with BRCA1 or BRCA2 PVs.
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Affiliation(s)
- Emma Zattarin
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Ida Taglialatela
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Riccardo Lobefaro
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Rita Leporati
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Giovanni Fucà
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Francesca Ligorio
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; IFOM ETS, the AIRC Institute of Molecular Oncology, Milan, Italy
| | - Caterina Sposetti
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Leonardo Provenzano
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Jacopo Azzollini
- Unit of Medical Genetics, Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Andrea Vingiani
- Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy; Pathology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Cristina Ferraris
- Breast Unit, Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Gabriele Martelli
- Breast Unit, Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Siranoush Manoukian
- Unit of Medical Genetics, Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Giancarlo Pruneri
- Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy; Pathology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Filippo de Braud
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
| | - Claudio Vernieri
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; IFOM ETS, the AIRC Institute of Molecular Oncology, Milan, Italy.
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30
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Orji P, Sun H, Isali I, Bell S, Zaorsky N, Mishra K, Gupta S, Correa A, Smaldone M, Calaway A, Viterbo R, Bukavina L. Female sexual function evaluation and intraoperative vaginal reconstruction in bladder cancer. World J Urol 2023; 41:1751-1762. [PMID: 37419972 DOI: 10.1007/s00345-023-04502-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Accepted: 05/12/2023] [Indexed: 07/09/2023] Open
Abstract
RC significantly negatively impacts sexual function (SF) in both men and women. While significant research resources have been allocated to examine the deleterious effects of post prostatectomy erectile dysfunction, little attention has been directed towards female sexual function and organ preservation post cystectomy. These academic shortcomings often result in poor provider awareness and inadequate preoperative assessment. As such, it is crucial for all providers involved in female RC care to understand the necessary and available tools for preoperative evaluation, in addition to the anatomic and reconstructive techniques. This review aims to summarize the current preoperative evaluation and available tools of SF assessment and describe in detail the varying operative techniques in the preservation or restoration of SF in women after RC. The review explores the intricacies of preoperative evaluation tools, and intraoperative techniques for organ- and nerve-sparing during radical cystectomy in females. Particular emphasis on vaginal reconstruction after partial or complete resection is provided, including split-thickness skin (STF) graft vaginoplasy, pedicled flaps, myocutaneous flaps and use of bowel segments. In conclusion, this narrative review highlights the importance of understanding anatomic considerations and nerve-sparing strategies in promoting postoperative SF and quality of life. Furthermore, the review describes the advantages and limitations of each organ- and nerve-sparing technique and their impact on sexual function and overall well-being.
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Affiliation(s)
- Peace Orji
- Case Western Reserve School of Medicine, Cleveland, OH, USA
| | - Helen Sun
- Case Western Reserve School of Medicine, Cleveland, OH, USA
- Department of Urology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Ilaha Isali
- Case Western Reserve School of Medicine, Cleveland, OH, USA
- Department of Urology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Spencer Bell
- Department of Urologic Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA
| | - Nicholas Zaorsky
- Case Western Reserve School of Medicine, Cleveland, OH, USA
- Department of Urology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Kirtishri Mishra
- Case Western Reserve School of Medicine, Cleveland, OH, USA
- Department of Urology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Shubham Gupta
- Case Western Reserve School of Medicine, Cleveland, OH, USA
- Department of Urology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Andres Correa
- Department of Urologic Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA
| | - Marc Smaldone
- Department of Urologic Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA
| | - Adam Calaway
- Case Western Reserve School of Medicine, Cleveland, OH, USA
- Department of Urology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Rosalia Viterbo
- Department of Urologic Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA
| | - Laura Bukavina
- Department of Urologic Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA.
- Department of Urologic Oncology, Fox Chase Cancer Center, Temple Health Medical Center, Philadelphia, PA, 19111, USA.
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31
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Chan LN, Chen LM, Goldman M, Mak JS, Bauer DC, Boscardin J, Schembri M, Bae-Jump V, Friedman S, Jacoby VL. Changes in Bone Density in Carriers of BRCA1 and BRCA2 Pathogenic Variants After Salpingo-Oophorectomy. Obstet Gynecol 2023; Publish Ahead of Print:00006250-990000000-00775. [PMID: 37290104 DOI: 10.1097/aog.0000000000005236] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Accepted: 03/23/2023] [Indexed: 06/10/2023]
Abstract
OBJECTIVE To evaluate the effect of risk-reducing salpingo-oophorectomy (RRSO) on change in bone mineral density (BMD) in women aged 34-50 years with pathogenic variants in BRCA1 or BRCA2 (BRCA1/2). METHODS The PROSper (Prospective Research of Outcomes after Salpingo-oophorectomy) study is a prospective cohort of women aged 34-50 years with BRCA1 or two germline pathogenic variants that compares health outcomes after RRSO to a non-RRSO control group with ovarian conservation. Women aged 34-50 years, who were planning either RRSO or ovarian conservation, were enrolled for 3 years of follow-up. Spine and total hip BMD were measured by dual-energy X-ray absorptiometry (DXA) scans obtained at baseline before RRSO or at the time of enrollment for the non-RRSO group, and then at 1 and 3 years of study follow-up. Differences in BMD between the RRSO and non-RRSO groups, as well as the association between hormone use and BMD, were determined by using mixed effects multivariable linear regression models. RESULTS Of 100 PROSper participants, 91 obtained DXA scans (RRSO group: 40; non-RRSO group: 51). Overall, total spine, and hip BMD decreased significantly from baseline to 12 months after RRSO (estimated percent change -3.78%, 95% CI -6.13% to -1.43% for total spine; -2.96%, 95% CI -4.79% to -1.14% for total hip) and at 36 months (estimated percent change -5.71%, 95% CI -8.64% to -2.77% for total spine; -5.19%, 95% CI -7.50% to -2.87% for total hip. In contrast, total spine and hip BMD were not significantly different from baseline for the non-RRSO group. The differences in mean percent change in BMD from baseline between the RRSO and non-RRSO groups were statistically significant at both 12 and 36 months for spine BMD (12-month difference -4.49%, 95% CI -7.67% to -1.31%; 36-month difference -7.06%, 95% CI -11.01% to -3.11%) and at 36 months for total hip BMD (12-month difference -1.83%, 95% CI -4.23% to 0.56%; 36-month difference -5.14%, 95% CI -8.11% to -2.16%). Across the study periods, hormone use was associated with significantly less bone loss at both the spine and hip within the RRSO group compared with no hormone use (P<.001 at both 12 months and 36 months) but did not completely prevent bone loss (estimated percent change from baseline at 36 months -2.79%, 95% CI -5.08% to -0.51% for total spine BMD; -3.93%, 95% CI -7.27% to -0.59% for total hip BMD). CONCLUSION Women with pathogenic variants in BRCA1/2 who undergo RRSO before the age of 50 years have greater bone loss after surgery that is clinically significant when compared with those who retain their ovaries. Hormone use mitigates, but does not eliminate, bone loss after RRSO. These results suggest that women who undergo RRSO may benefit from routine screening for BMD changes to identify opportunities for prevention and treatment of bone loss. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, NCT01948609.
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Affiliation(s)
- Leslie N Chan
- School of Medicine, the Department of Obstetrics, Gynecology and Reproductive Sciences, the Helen Diller Family Comprehensive Cancer Center, the Department of Medicine, and the Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, San Francisco, California; the Division of Gynecology Oncology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; and Facing Our Risk of Cancer Empowered, Tampa, Florida
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32
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Stadler ZK, Schrag D. Genetic Testing for Cancer Susceptibility. JAMA 2023:2805797. [PMID: 37276548 DOI: 10.1001/jama.2023.9474] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/07/2023]
Affiliation(s)
- Zsofia K Stadler
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Deborah Schrag
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
- Associate Editor, JAMA
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33
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Goh V. Genitourinary Imaging in 2040. Radiology 2023; 307:e230223. [PMID: 37249430 PMCID: PMC10315527 DOI: 10.1148/radiol.230223] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 02/03/2023] [Accepted: 02/06/2023] [Indexed: 05/31/2023]
Affiliation(s)
- Vicky Goh
- From the Department of Cancer Imaging, School of Biomedical
Engineering and Imaging Sciences, King’s College London, SE1 7EH,
United Kingdom; and Department of Radiology, Guy’s & St
Thomas’ NHS Foundation Trust, Level 1, Lambeth Wing, St Thomas’
Hospital, Westminster Bridge Rd, London, United Kingdom
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34
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Onji M, Penninger JM. RANKL and RANK in Cancer Therapy. Physiology (Bethesda) 2023; 38:0. [PMID: 36473204 DOI: 10.1152/physiol.00020.2022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Receptor activator of nuclear factor-κB (RANK) and its ligand (RANKL) are key regulators of mammalian physiology such as bone metabolism, immune tolerance and antitumor immunity, and mammary gland biology. Here, we explore the multiple functions of RANKL/RANK in physiology and pathophysiology and discuss underlying principles and strategies to modulate the RANKL/RANK pathway as a therapeutic target in immune-mediated cancer treatment.
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Affiliation(s)
- Masahiro Onji
- Institute of Molecular Biotechnology of the Austrian Academy of Sciences, VBC-Vienna BioCenter, Vienna, Austria
| | - Josef M Penninger
- Institute of Molecular Biotechnology of the Austrian Academy of Sciences, VBC-Vienna BioCenter, Vienna, Austria.,Department of Medical Genetics, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada
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35
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Schünemann J, Strulik H, Trimborn T. Anticipation of deteriorating health and information avoidance. JOURNAL OF HEALTH ECONOMICS 2023; 89:102755. [PMID: 37004358 DOI: 10.1016/j.jhealeco.2023.102755] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Revised: 02/15/2023] [Accepted: 03/20/2023] [Indexed: 06/19/2023]
Abstract
We integrate anticipatory utility and endogenous beliefs about future negative health shocks into a life-cycle model of physiological aging. Individuals care about their future utility derived from their health status and form endogenous beliefs about the probability of a negative health shock. We calibrate the model with data from gerontology and use the model to predict medical testing decisions of individuals. We find that anticipation in combination with endogenous beliefs provides a quantitatively strong motive to avoid medical testing for Huntington's disease, which explains the low testing rates found empirically. We also study the case of breast and ovarian cancer and provide an explanation for why testing rates depend on the individual's income when treatment is available.
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Affiliation(s)
- Johannes Schünemann
- University of Fribourg, Department of Economics, Bd. de Perolles 90, 1700 Fribourg, Switzerland.
| | - Holger Strulik
- University of Goettingen, Department of Economics, Platz der Goettinger Sieben 3, 37073 Goettingen, Germany.
| | - Timo Trimborn
- Aarhus University, Department of Economics and Business Economics, Fuglesangs Allé 4, 8210 Aarhus V, Denmark.
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36
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Schwartz ZP, Li AJ, Walsh CS, Rimel BJ, Alvarado MM, Lentz SE, Cass I. Patterns of care and outcomes of risk reducing surgery in women with pathogenic variants in non-BRCA and Lynch syndrome ovarian cancer susceptibility genes. Gynecol Oncol 2023; 173:1-7. [PMID: 37030072 DOI: 10.1016/j.ygyno.2023.03.017] [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: 12/30/2022] [Revised: 03/22/2023] [Accepted: 03/23/2023] [Indexed: 04/10/2023]
Abstract
OBJECTIVES Guidelines recommend risk-reducing bilateral salpingo-oophorectomy (RRSO) for women with pathogenic variants of non-BRCA and Lynch syndrome-associated ovarian cancer susceptibility genes. Optimal timing and findings at the time of RRSO for these women remains unclear. We sought to characterize practice patterns and frequency of occult gynecologic cancers for these women at our two institutions. METHODS Women with germline ovarian cancer susceptibility gene pathogenic variants who underwent RRSO between 1/2000-9/2019 were reviewed in an IRB-approved study. All patients were asymptomatic with no suspicion for malignancy at time of RRSO. Clinico-pathologic characteristics were extracted from the medical records. RESULTS 26 Non-BRCA (9 BRIP1, 9 RAD51C, and 8 RAD51D) and 75 Lynch (36 MLH1, 18 MSH2, 21 MSH6) pathogenic variants carriers were identified. Median age at time of RRSO was 47. There were no occurrences of occult ovarian or fallopian tube cancer in either group. Two patients (3%) in the Lynch group had occult endometrial cancer. Median follow up was 18 and 35 months for non-BRCA and Lynch patients, respectively. No patient developed primary peritoneal cancer upon follow up. Post-surgical complications occurred in 9/101 (9%) of patients. Hormone replacement therapy (HRT) was rarely used despite reported post-menopausal symptoms in 6/25 (23%) and 7/75 (37%) patients, respectively. CONCLUSIONS No occult ovarian or tubal cancers were observed in either group. No recurrent or primary gynecologic-related cancers occurred upon follow-up. Despite frequent menopausal symptoms, HRT use was rare. Both groups experienced surgical complications when hysterectomy and/or concurrent colon surgery was performed suggesting concurrent surgeries should only be performed when indicated.
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Affiliation(s)
- Zachary P Schwartz
- Kaiser Permanente Panorama City Medical Center, Division of Gynecologic Oncology, 13640 Roscoe Blvd., Panorama City, CA 91402, USA.
| | - Andrew J Li
- Cedars-Sinai Medical Center, Samuel Oschin Cancer Center, 127 S. San Vicente Blvd., 7th Floor, Los Angeles, CA 90048, USA.
| | - Christine S Walsh
- University of Colorado Cancer Center, 1665 Aurora Court, Aurora, CO 80045, USA.
| | - B J Rimel
- Cedars-Sinai Medical Center, Samuel Oschin Cancer Center, 127 S. San Vicente Blvd., 7th Floor, Los Angeles, CA 90048, USA.
| | - Monica M Alvarado
- Kaiser Permanente Southern California Regional Genetic Services, 393 E. Walnut St. 6 SW, Pasadena, CA 91188, USA.
| | - Scott E Lentz
- Kaiser Permanente Los Angeles Medical Center, Gynecology Oncology Department, 4950 W., Sunset Blvd., Los Angeles, CA 90027, USA.
| | - Ilana Cass
- Dartmouth Hitchcock Medical Center, Department of Obstetrics and Gynecology, 1 Medical, Center Drive, Lebanon, NH 03756, USA.
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Terao Y. Cutting-edge Treatment for Gynecological Malignancies. JUNTENDO IJI ZASSHI = JUNTENDO MEDICAL JOURNAL 2023; 69:86-91. [PMID: 38854450 PMCID: PMC11153064 DOI: 10.14789/jmj.jmj22-0044-r] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Accepted: 01/16/2023] [Indexed: 06/11/2024]
Abstract
Gynecological malignant tumors can develop in the vulva, vagina, uterus, fallopian tubes, or ovaries in the female reproductive tract. The cervix, uterine body, and ovaries are particularly common sites for malignant tumors. Surgery, radiation, and drug therapy are the main treatment modalities for gynecological cancers, with surgery being the most important of them. We started laparoscopic surgery for uterine endometrial cancer as an advanced medical treatment in 2011 and contributed to its insurance coverage. We were able to reproduce our laparoscopic surgery more easily using the da Vinci Xi system for robotic surgery. We have now switched from laparoscopic surgery for endometrial cancer to robotic surgery and have been able to perform them safely and reliably. In the case of cervical cancer, the results of the Laparoscopic Approach to Cervical Cancer (LACC) trial, which compared the prognosis of two groups of radical hysterectomy for early-stage cervical cancer: conventional open surgery and laparoscopic/robotic (minimally invasive) surgery, showed that minimally invasive surgery resulted in more pelvic recurrences and had a worse prognosis compared with open surgery. The trend toward minimally invasive surgery for cervical cancer has stagnated worldwide. Ovarian cancer has few symptoms in the early stages and is often found at stage III or IV, when the cancer has spread throughout the abdominal cavity. As residual tumor after surgery correlates with prognosis in ovarian cancer, debulking surgery should be performed to achieve complete resection. Therefore, peritoneal or bowel resection is often required to remove disseminated or metastatic tumors. We also performed prophylactic salpingo-oophorectomy to prevent ovarian and fallopian tube cancers in patients with BRCA1/2 gene variants. The uterus and ovaries are organs necessary for pregnancy and childbirth, and cancer of the uterus or ovaries in women of childbearing age may result in infertility. Surgery and adjuvant treatment may affect marriage, childbirth, and sexual life; therefore, it is important to ensure the cure of cancer and to provide patients with treatment methods that allow them to live their lives as women.
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Gaba F, Blyuss O, Tan A, Munblit D, Oxley S, Khan K, Legood R, Manchanda R. Breast Cancer Risk and Breast-Cancer-Specific Mortality following Risk-Reducing Salpingo-Oophorectomy in BRCA Carriers: A Systematic Review and Meta-Analysis. Cancers (Basel) 2023; 15:cancers15051625. [PMID: 36900415 PMCID: PMC10001253 DOI: 10.3390/cancers15051625] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Revised: 02/20/2023] [Accepted: 03/02/2023] [Indexed: 03/09/2023] Open
Abstract
BACKGROUND Risk-reducing salpingo-oophorectomy (RRSO) is the gold standard method of ovarian cancer risk reduction, but the data are conflicting regarding the impact on breast cancer (BC) outcomes. This study aimed to quantify BC risk/mortality in BRCA1/BRCA2 carriers after RRSO. METHODS We conducted a systematic review (CRD42018077613) of BRCA1/BRCA2 carriers undergoing RRSO, with the outcomes including primary BC (PBC), contralateral BC (CBC) and BC-specific mortality (BCSM) using a fixed-effects meta-analysis, with subgroup analyses stratified by mutation and menopause status. RESULTS RRSO was not associated with a significant reduction in the PBC risk (RR = 0.84, 95%CI: 0.59-1.21) or CBC risk (RR = 0.95, 95%CI: 0.65-1.39) in BRCA1 and BRCA2 carriers combined but was associated with reduced BC-specific mortality in BC-affected BRCA1 and BRCA2 carriers combined (RR = 0.26, 95%CI: 0.18-0.39). Subgroup analyses showed that RRSO was not associated with a reduction in the PBC risk (RR = 0.89, 95%CI: 0.68-1.17) or CBC risk (RR = 0.85, 95%CI: 0.59-1.24) in BRCA1 carriers nor a reduction in the CBC risk in BRCA2 carriers (RR = 0.35, 95%CI: 0.07-1.74) but was associated with a reduction in the PBC risk in BRCA2 carriers (RR = 0.63, 95%CI: 0.41-0.97) and BCSM in BC-affected BRCA1 carriers (RR = 0.46, 95%CI: 0.30-0.70). The mean NNT = 20.6 RRSOs to prevent one PBC death in BRCA2 carriers, while 5.6 and 14.2 RRSOs may prevent one BC death in BC-affected BRCA1 and BRCA2 carriers combined and BRCA1 carriers, respectively. CONCLUSIONS RRSO was not associated with PBC or CBC risk reduction in BRCA1 and BRCA2 carriers combined but was associated with improved BC survival in BC-affected BRCA1 and BRCA2 carriers combined and BRCA1 carriers and a reduced PBC risk in BRCA2 carriers.
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Affiliation(s)
- Faiza Gaba
- Institute of Applied Health Sciences, University of Aberdeen, Aberdeen AB24 3FX, UK
- Department of Gynaecological Oncology, Barts Health NHS Trust, London E1 1FR, UK
| | - Oleg Blyuss
- Wolfson Institute of Population Health, Barts CRUK Cancer Centre, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK
- Department of Paediatrics and Paediatric Infectious Diseases, Institute of Child’s Health, Sechenov First Moscow State Medical University (Sechenov University), 29 Shmitovskiy Proezd, 123337 Moscow, Russia
| | - Alex Tan
- Wolfson Institute of Population Health, Barts CRUK Cancer Centre, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK
| | - Daniel Munblit
- Department of Paediatrics and Paediatric Infectious Diseases, Institute of Child’s Health, Sechenov First Moscow State Medical University (Sechenov University), 29 Shmitovskiy Proezd, 123337 Moscow, Russia
- Care for Long Term Conditions Division, Florence Nightingale Faculty of Nursing Midwifery and Palliative Care, King’s College London, London SE1 8WA, UK
- Solov’ev Research and Clinical Center for Neuropsychiatry, 43 Ulitsa Donskaya, 115419 Moscow, Russia
| | - Samuel Oxley
- Department of Gynaecological Oncology, Barts Health NHS Trust, London E1 1FR, UK
- Wolfson Institute of Population Health, Barts CRUK Cancer Centre, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK
| | - Khalid Khan
- Department of Preventive Medicine and Public Health, Universidad de Granada, 18071 Granada, Spain
| | - Rosa Legood
- Department of Health Services Research and Policy, London School of Hygiene & Tropical Medicine, London WC1H 9SH, UK
| | - Ranjit Manchanda
- Department of Gynaecological Oncology, Barts Health NHS Trust, London E1 1FR, UK
- Wolfson Institute of Population Health, Barts CRUK Cancer Centre, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK
- Department of Health Services Research and Policy, London School of Hygiene & Tropical Medicine, London WC1H 9SH, UK
- MRC Clinical Trials Unit, University College London, 90 High Holborn, London WC1V 6LJ, UK
- Department of Gynaecology, All India Institute of Medical Sciences, New Delhi 110029, India
- Correspondence:
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39
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AlHilli MM, Batur P, Hurley K, Al-Hilli Z, Coombs D, Schwarz G, Djohan R, Marquard J, Ashton K, Pederson HJ. Comprehensive Care of Women With Genetic Predisposition to Breast and Ovarian Cancer. Mayo Clin Proc 2023; 98:597-609. [PMID: 36870859 DOI: 10.1016/j.mayocp.2023.01.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Revised: 12/16/2022] [Accepted: 01/03/2023] [Indexed: 03/06/2023]
Abstract
Women at risk for hereditary breast and ovarian cancer syndromes are frequently seen in primary care and gynecology clinics. They present with a distinctive set of clinical and emotional needs that revolve around complex risk management discussions and decision making. The care of these women calls for the creation of individualized care plans that facilitate adjustment to the mental and physical changes associated with their choices. This article provides an update on comprehensive evidence-driven care of women with hereditary breast and ovarian cancer. The aim of this review is to aid clinicians in identifying those at risk for hereditary cancer syndromes and provide practical advice on patient-centered medical and surgical risk management. Topics of discussion include enhanced surveillance, preventive medications, risk-reducing mastectomy and reconstruction, risk-reducing bilateral salpingo-oophorectomy, fertility, sexuality, and menopausal management, with attention to the importance of psychological support. High-risk patients may benefit from a multidisciplinary team that provides realistic expectations with consistent messaging. The primary care provider must be aware of the special needs of these patients and the consequences of their risk management interventions.
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Affiliation(s)
- Mariam M AlHilli
- Department of Subspecialty Care for Women's Health, Division of Gynecologic Oncology, Ob/Gyn & Women's Health Institute, Cleveland Clinic, Cleveland, OH; Department of Subspecialty Care for Women's Health, Ob/Gyn & Women's Health Institute, Cleveland Clinic, Cleveland, OH.
| | - Pelin Batur
- Department of Subspecialty Care for Women's Health, Ob/Gyn & Women's Health Institute, Cleveland Clinic, Cleveland, OH
| | - Karen Hurley
- Center for Behavioral Health, Department of Psychiatry & Psychology, Neurological Institute, Cleveland Clinic, Cleveland, OH
| | - Zahraa Al-Hilli
- Department of General Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH
| | - Demetrius Coombs
- Center for Behavioral Health, Department of Psychiatry & Psychology, Neurological Institute, Cleveland Clinic, Cleveland, OH; Department of Plastic Surgery, Cleveland Clinic, Cleveland, OH
| | - Graham Schwarz
- Department of Plastic Surgery, Cleveland Clinic, Cleveland, OH
| | - Risal Djohan
- Department of Plastic Surgery, Cleveland Clinic, Cleveland, OH
| | | | - Kathleen Ashton
- Breast Center, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH
| | - Holly J Pederson
- Breast Center, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH
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40
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Manley K, Ryan N, Jenner A, Newton C, Hillard T. Counselling of path_ BRCA carriers who are considering risk-reducing oophorectomy. Post Reprod Health 2023; 29:42-52. [PMID: 36757900 DOI: 10.1177/20533691231156640] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/10/2023]
Abstract
path_BRCA 1/2 increases a woman's lifetime risk of breast and ovarian cancer. Interventions can be offered which manage cancer risk; annual breast screening from age 30, chemoprevention and, once a woman's family is complete, risk-reducing surgery. The latter is the most effective method of reducing cancer in path_BRCA carriers; salpingo-oophorectomy reduces breast and ovarian cancer, respectively, by up to 50% and 95%. Factors affecting a woman's decision to undergo risk-reducing surgery are complex; dominant factors include risks of surgery, effect on cancer outcomes and menopausal sequelae. Specific information relating to hormone replacement and non-hormonal alternatives are an important consideration for women but, are often overlooked. Informative counselling is required to enable satisfaction with the chosen intervention whilst improving survival outcomes. This review paper outlines the current data pertaining to these decision-making factors and provides a proforma to enable effective counselling.
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Affiliation(s)
- Kristyn Manley
- Department of Gynaecology, 1984University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK
- The Academic Women's Health Unit, Translational Women's Health Sciences, 152004University of Bristol, Bristol, UK
| | - Neil Ryan
- The Academic Women's Health Unit, Translational Women's Health Sciences, 152004University of Bristol, Bristol, UK
- Department of Gynaecology Oncology, Royal Infirmary of Edinburgh, Edinburgh
| | - Abigail Jenner
- Department of Gynaecology, 1984University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK
- Department of Oncology, 1556Royal United Hospitals Bath, Bath, UK
| | - Claire Newton
- Department of Gynaecology, 1984University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK
- The Academic Women's Health Unit, Translational Women's Health Sciences, 152004University of Bristol, Bristol, UK
| | - Timothy Hillard
- Department of Gynaecology, 6655University Hospitals Dorset, Poole, UK
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41
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Bahar-Shany K, Barnabas GD, Deutsch L, Deutsch N, Glick-Saar E, Dominissini D, Sapoznik S, Helpman L, Perri T, Blecher A, Katz G, Yagel I, Rosenblatt O, Shai D, Brandt B, Meyer R, Mohr-Sasson A, Volodarsky-Perel A, Zilberman I, Armon S, Jakobson-Setton A, Eitan R, Kadan Y, Beiner M, Josephy D, Brodsky M, Friedman E, Anafi L, Molchanov Y, Korach J, Geiger T, Levanon K. Proteomic signature for detection of high-grade ovarian cancer in germline BRCA mutation carriers. Int J Cancer 2023; 152:781-793. [PMID: 36214786 DOI: 10.1002/ijc.34318] [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: 03/15/2022] [Revised: 08/21/2022] [Accepted: 09/05/2022] [Indexed: 02/01/2023]
Abstract
No current screening methods for high-grade ovarian cancer (HGOC) guarantee effective early detection for high-risk women such as germline BRCA mutation carriers. Therefore, the standard-of-care remains risk-reducing salpingo-oophorectomy (RRSO) around age 40. Proximal liquid biopsy is a promising source of biomarkers, but sensitivity has not yet qualified for clinical implementation. We aimed to develop a proteomic assay based on proximal liquid biopsy, as a decision support tool for monitoring high-risk population. Ninety Israeli BRCA1 or BRCA2 mutation carriers were included in the training set (17 HGOC patients and 73 asymptomatic women), (BEDOCA trial; ClinicalTrials.gov Identifier: NCT03150121). The proteome of the microvesicle fraction of the samples was profiled by mass spectrometry and a classifier was developed using logistic regression. An independent cohort of 98 BRCA mutation carriers was used for validation. Safety information was collected for all women who opted for uterine lavage in a clinic setting. We present a 7-protein diagnostic signature, with AUC >0.97 and a negative predictive value (NPV) of 100% for detecting HGOC. The AUC of the biomarker in the independent validation set was >0.94 and the NPV >99%. The sampling procedure was clinically acceptable, with favorable pain scores and safety. We conclude that the acquisition of Müllerian tract proximal liquid biopsies in women at high-risk for HGOC and the application of the BRCA-specific diagnostic assay demonstrates high sensitivity, specificity, technical feasibility and safety. Similar classifier for an average-risk population is warranted.
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Affiliation(s)
- Keren Bahar-Shany
- Sheba Cancer Research Center, Chaim Sheba Medical Center, Ramat Gan, Israel
| | - Georgina D Barnabas
- Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel
| | - Lisa Deutsch
- BioStats, Statistical Consulting Ltd, Modiin, Israel
| | | | - Efrat Glick-Saar
- Sheba Cancer Research Center, Chaim Sheba Medical Center, Ramat Gan, Israel
| | - Dan Dominissini
- Sheba Cancer Research Center, Chaim Sheba Medical Center, Ramat Gan, Israel.,Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Israel
| | - Stav Sapoznik
- Sheba Cancer Research Center, Chaim Sheba Medical Center, Ramat Gan, Israel
| | - Limor Helpman
- Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Israel.,Department of Gynecologic Oncology, Chaim Sheba Medical Center, Ramat Gan, Israel
| | - Tamar Perri
- Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Israel.,Department of Gynecologic Oncology, Chaim Sheba Medical Center, Ramat Gan, Israel
| | - Anna Blecher
- Department of Gynecologic Oncology, Chaim Sheba Medical Center, Ramat Gan, Israel
| | - Guy Katz
- Department of Gynecologic Oncology, Chaim Sheba Medical Center, Ramat Gan, Israel
| | - Itai Yagel
- Department of Gynecologic Oncology, Chaim Sheba Medical Center, Ramat Gan, Israel
| | - Orgad Rosenblatt
- Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Israel.,Department of Gynecologic Oncology, Chaim Sheba Medical Center, Ramat Gan, Israel
| | - Daniel Shai
- Department of Gynecologic Oncology, Chaim Sheba Medical Center, Ramat Gan, Israel
| | - Benny Brandt
- Department of Gynecologic Oncology, Chaim Sheba Medical Center, Ramat Gan, Israel
| | - Raanan Meyer
- Division of Obstetrics and Gynecology, Chaim Sheba Medical Center, Ramat Gan, Israel
| | - Aya Mohr-Sasson
- Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Israel.,Division of Obstetrics and Gynecology, Chaim Sheba Medical Center, Ramat Gan, Israel
| | | | - Itamar Zilberman
- Division of Obstetrics and Gynecology, Chaim Sheba Medical Center, Ramat Gan, Israel
| | - Shunit Armon
- Department of Obstetrics & Gynecology, Shaare Zedek Medical Center, Jerusalem, Israel
| | - Ariella Jakobson-Setton
- Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Israel.,Department of Gynecologic Oncology, Rabin Medical Center, Petah Tikva, Israel
| | - Ram Eitan
- Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Israel.,Department of Gynecologic Oncology, Rabin Medical Center, Petah Tikva, Israel
| | - Yfat Kadan
- Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Israel.,Division of Gynecologic Oncology, Meir Medical Center, Kfar Saba, Israel
| | - Mario Beiner
- Division of Gynecologic Oncology, Meir Medical Center, Kfar Saba, Israel
| | - Dana Josephy
- Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Israel.,Division of Gynecologic Oncology, Meir Medical Center, Kfar Saba, Israel
| | - Malka Brodsky
- Meirav Breast Health Center, Chaim Sheba Medical Center, Ramat Gan, Israel
| | - Eitan Friedman
- Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Israel.,The Susanne-Levy Gertner Oncogenetics Unit, Chaim Sheba Medical Center, Ramat Gan, Israel
| | - Liat Anafi
- Department of Pathology, Chaim Sheba Medical Center, Ramat Gan, Israel
| | - Yossef Molchanov
- Department of Pathology, Chaim Sheba Medical Center, Ramat Gan, Israel
| | - Jacob Korach
- Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Israel.,Department of Gynecologic Oncology, Chaim Sheba Medical Center, Ramat Gan, Israel
| | - Tamar Geiger
- Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel.,Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
| | - Keren Levanon
- Sheba Cancer Research Center, Chaim Sheba Medical Center, Ramat Gan, Israel.,Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Israel
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42
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Robson M. Testing for Inherited Susceptibility to Breast Cancer. Hematol Oncol Clin North Am 2023; 37:17-31. [PMID: 36435609 DOI: 10.1016/j.hoc.2022.08.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
When BRCA1 and BRCA2 were first identified, the initial models for delivering testing were shaped by concepts of genetic exceptionalism and a lack of data regarding therapeutic implications and the effectiveness of risk reduction. Since then, interventions have been effective, and treatment implications have become clear. The sensitivity of guideline-based testing is incomplete, leading to calls for universal testing. Completely universal testing, however, is not necessary to identify the great majority of BRCA1 or BRCA2 variants. Broader testing (both in terms of eligibility and genes tested) will identify more variants, particularly in moderate penetrance genes, but the clinical implications remain less clear for these variants.
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Affiliation(s)
- Mark Robson
- Breast Medicine Service, Department of Medicine, Memorial Hospital for Treatment of Cancer and Allied Disease, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, 300 East 66th Street, Room 813, New York, NY 10065, USA.
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43
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Hayashi T, Konishi I. Molecular Histopathology for Establishing Diagnostic Method and Clinical Therapy for Ovarian Carcinoma. J Clin Med Res 2023; 15:68-75. [PMID: 36895622 PMCID: PMC9990723 DOI: 10.14740/jocmr4853] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2022] [Accepted: 02/11/2023] [Indexed: 03/04/2023] Open
Abstract
Ovarian carcinoma (OC) is considered the deadliest gynecological malignancy. It is typically diagnosed in the advanced stages of the disease, with metastatic sites widely disseminated within the abdominal cavity. OC treatment is challenging due to the high rate of disease recurrence, which is further complicated by acquired chemoresistance caused by the reversion of the pathological variant. Therefore, more effective treatments are still being sought. Histologically, OC is classified into serous, mucinous, endometrioid, clear cell, and transitional cell carcinomas and malignant Brenner tumor. Recent clinicopathological and molecular biological studies demonstrated that these subtypes differ in histogenesis and anti-tumor agent sensitivity. In Japan, the incidence rates of the histological types of OC, namely, serous carcinoma, mucinous carcinoma, endometrioid carcinoma, and clear cell adenocarcinoma, are 39%, 12%, 16%, and 23%, respectively. Serous carcinoma is classified as high or low grade, with the former accounting for the overwhelming majority. In this study, the molecular pathological classification of OC has been described based on the characteristics of the two types of OC, types 1 and 2. Compared with Europe and the United States, Japan has a higher prevalence of type 1 OC and a lower prevalence of type 2 OC. The prevalence of each type of OC varies by race. It has been elucidated that the prevalence rate of each type of ovarian cancer in Asian countries is similar to that in Japan. Thus, OC is a heterogeneous disease. Furthermore, OC has been attributed to molecular biological mechanisms that vary among tissue subtypes. Therefore, it is necessary to conduct treatment based on accurate diagnoses of each tissue type and establish an optimal treatment strategy, and now is the transition period.
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Affiliation(s)
- Takuma Hayashi
- National Hospital Organization Kyoto Medical Center, Fukakusa Mukaihata-cho, Kyoto 612-8555, Japan
| | - Ikuo Konishi
- National Hospital Organization Kyoto Medical Center, Fukakusa Mukaihata-cho, Kyoto 612-8555, Japan
- Kyoto University, Graduate School of Medicine, Sakyo-ku, Kyoto 606-8507, Japan
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44
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Long-Term Non-Cancer Risks in People with BRCA Mutations following Risk-Reducing Bilateral Salpingo-Oophorectomy and the Role of Hormone Replacement Therapy: A Review. Cancers (Basel) 2023; 15:cancers15030711. [PMID: 36765666 PMCID: PMC9913268 DOI: 10.3390/cancers15030711] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Revised: 01/19/2023] [Accepted: 01/21/2023] [Indexed: 01/26/2023] Open
Abstract
Risk-reducing bilateral salpingo-oophorectomy (RRBSO) is the gold standard preventative option for BRCA mutation carriers at high risk for ovarian and breast cancer. However, when performed at the recommended ages of 35-45 years, RRBSO induces immediate premature surgical menopause, along with the accompanying adverse psychosocial, cardiovascular, bone, and cognitive health consequences. While these health consequences have been thoroughly studied in the general population, little is known about the long-term health outcomes in the BRCA population. Hormone replacement therapy (HRT) until the average age of natural menopause can help mitigate these health risks, yet the initiation of HRT is a complex decision among BRCA carriers due to concern of increasing the already high risk of breast cancer in these people. This review summarizes the current research on long-term non-cancer risks in BRCA carriers following RRBSO-induced premature surgical menopause, and highlights the existing evidence in support of HRT use in this population.
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45
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Global Oncology Medical Diplomacy Working Group Inaugural Meeting: Defining Worldwide Barriers to Germline Genomics in Cancer Prevention and Management. Ann Glob Health 2023; 89:16. [PMID: 36843667 PMCID: PMC9951627 DOI: 10.5334/aogh.3967] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2022] [Accepted: 12/22/2022] [Indexed: 02/23/2023] Open
Abstract
We convened an international working group to examine the issues that challenge equity and inclusion in genetic medicine. Specifically, 72 internationally known experts in oncology and cancer genetics from 34 countries (the Global Oncology Medical Diplomacy Working Group), gathered virtually on January 4-5, 2022, for the "Humanity Cancer Germline Convergence and Divergence Cancer Predispositions" conference hosted by Memorial Sloan Kettering Cancer Center, in collaboration with the United Arab Emirates Ministry of Health and the Al Jalila Foundation. The goal of the conference was to broaden transnational understanding of the current state of genetics in preventive and therapeutic cancer medicine, and to define barriers to increased uptake of germline genomics to decrease the international burden of cancer. Here, we highlight the overarching barriers that were defined through this effort. These global barriers to incorporating germline genomics into optimal cancer care can inform ongoing research, collaboration, and advocacy for equitable, cost-effective genomic medicine for populations worldwide.
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46
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Abe A, Imoto I, Ueki A, Nomura H, Kanao H. Moderate-Risk Genes for Hereditary Ovarian Cancers Involved in the Homologous Recombination Repair Pathway. Int J Mol Sci 2022; 23:11790. [PMID: 36233090 PMCID: PMC9570179 DOI: 10.3390/ijms231911790] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Revised: 09/29/2022] [Accepted: 09/30/2022] [Indexed: 11/17/2022] Open
Abstract
Approximately 20% of cases of epithelial ovarian cancer (EOC) are hereditary, sharing many causative genes with breast cancer. The lower frequency of EOC compared to breast cancer makes it challenging to estimate absolute or relative risk and verify the efficacy of risk-reducing surgery in individuals harboring germline pathogenic variants (GPV) in EOC predisposition genes, particularly those with relatively low penetrance. Here, we review the molecular features and hereditary tumor risk associated with several moderate-penetrance genes in EOC that are involved in the homologous recombination repair pathway, i.e., ATM, BRIP1, NBN, PALB2, and RAD51C/D. Understanding the molecular mechanisms underlying the expression and function of these genes may elucidate trends in the development and progression of hereditary tumors, including EOC. A fundamental understanding of the genes driving EOC can help us accurately estimate the genetic risk of developing EOC and select appropriate prevention and treatment strategies for hereditary EOC. Therefore, we summarize the functions of the candidate predisposition genes for EOC and discuss the clinical management of individuals carrying GPV in these genes.
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Affiliation(s)
- Akiko Abe
- Department of Gynecologic Oncology, Cancer Institute Hospital of JFCR, Tokyo 135-8550, Japan
| | - Issei Imoto
- Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan
| | - Arisa Ueki
- Clinical Genetic Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan
| | - Hidetaka Nomura
- Department of Gynecologic Oncology, Cancer Institute Hospital of JFCR, Tokyo 135-8550, Japan
| | - Hiroyuki Kanao
- Department of Gynecologic Oncology, Cancer Institute Hospital of JFCR, Tokyo 135-8550, Japan
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47
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Smallwood KG, Crockett S, Huang V, Cullimore V, Davies J, Satti G, Phillips A. Changing patterns of referral into a family history clinic and detection of ovarian cancer: a retrospective 10-year review. J OBSTET GYNAECOL 2022; 42:2652-2658. [PMID: 35980980 DOI: 10.1080/01443615.2022.2111253] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
This study examines whether a change in the criteria for genetic testing for ovarian cancer risk changed the nature of referrals into our Familial Cancer service. This is a retrospective review of 273 women who underwent risk reducing surgery (RRS). The primary outcome was to establish whether there was an increase in women having RRS with a confirmed genetic mutation. Secondary outcomes included the incidence of occult cancer and of subsequent primary peritoneal cancer. The results showed an increase in women being offered RRS based on genetic diagnosis; 91% versus 32% before the criteria change. Four occult malignancies (1.5%) and two peritoneal cancers (0.7%) were noted.We have demonstrated a change in the nature of referrals to the familial cancer service from perceived risk to genetic diagnosis. We can now counsel women more accurately. With a defined risk we are enabling them to make an informed decision regarding risk reduction.
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Affiliation(s)
- K G Smallwood
- Department of Obstetrics and Gynaecology, University Hospitals of Derby and Burton, Derby, UK
| | - S Crockett
- Department of Familial Cancer, University Hospitals of Derby and Burton, Derby, UK
| | - V Huang
- Medical School, University of Nottingham, Nottingham, UK
| | - V Cullimore
- Department of Obstetrics and Gynaecology, University Hospitals of Derby and Burton, Derby, UK
| | - J Davies
- Department of Obstetrics and Gynaecology, University Hospitals of Derby and Burton, Derby, UK
| | - G Satti
- Department of Obstetrics and Gynaecology, University Hospitals of Derby and Burton, Derby, UK
| | - A Phillips
- Department of Obstetrics and Gynaecology, University Hospitals of Derby and Burton, Derby, UK
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48
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Ghose A, Bolina A, Mahajan I, Raza SA, Clarke M, Pal A, Sanchez E, Rallis KS, Boussios S. Hereditary Ovarian Cancer: Towards a Cost-Effective Prevention Strategy. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph191912057. [PMID: 36231355 PMCID: PMC9565024 DOI: 10.3390/ijerph191912057] [Citation(s) in RCA: 47] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/04/2022] [Revised: 09/20/2022] [Accepted: 09/21/2022] [Indexed: 05/25/2023]
Abstract
Ovarian cancer (OC) is the most lethal gynaecological malignancy. The search for a widely affordable and accessible screening strategy to reduce mortality from OC is still ongoing. This coupled with the late-stage presentation and poor prognosis harbours significant health-economic implications. OC is also the most heritable of all cancers, with an estimated 25% of cases having a hereditary predisposition. Advancements in technology have detected multiple mutations, with the majority affecting the BRCA1 and/or BRCA2 genes. Women with BRCA mutations are at a significantly increased lifetime risk of developing OC, often presenting with a high-grade serous pathology, which is associated with higher mortality due to its aggressive characteristic. Therefore, a targeted, cost-effective approach to prevention is paramount to improve clinical outcomes and mortality. Current guidelines offer multiple preventive strategies for individuals with hereditary OC (HOC), including genetic counselling to identify the high-risk women and risk-reducing interventions (RRI), such as surgical management or chemoprophylaxis through contraceptive medications. Evidence for sporadic OC is abundant as compared to the existing dearth in the hereditary subgroup. Hence, our review article narrates an overview of HOC and explores the RRI developed over the years. It attempts to compare the cost effectiveness of these strategies with women of the general population in order to answer the crucial question: what is the most prudent clinically and economically effective strategy for prevention amongst high-risk women?
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Affiliation(s)
- Aruni Ghose
- Department of Medical Oncology, Barts Cancer Centre, St. Bartholomew’s Hospital, Barts Health NHS Trust, London E1 1BB, UK
- Department of Medical Oncology, Mount Vernon Cancer Centre, East and North Hertfordshire NHS Trust, London SG1 4AB, UK
- Department of Medical Oncology, Medway NHS Foundation Trust, Gillingham ME7 5NY, UK
| | - Anita Bolina
- Department of Medical Oncology, Clatterbridge Cancer Centre, Clatterbridge Cancer Centre NHS Foundation Trust, Liverpool CH63 4JY, UK
| | - Ishika Mahajan
- Department of Medical Oncology, Apollo Cancer Centre, Chennai 600001, India
| | - Syed Ahmer Raza
- Department of Internal Medicine, St. Thomas’ Hospital, Guy’s and St. Thomas’ NHS Foundation Trust, London SE1 7EH, UK
| | - Miranda Clarke
- Department of Internal Medicine, Royal London Hospital, Barts Health NHS Trust, London E1 1BB, UK
| | - Abhinanda Pal
- Department of Internal Medicine, IQ City Medical College and Narayana Hospital, Durgapur 713206, India
| | - Elisabet Sanchez
- Department of Medical Oncology, Medway NHS Foundation Trust, Gillingham ME7 5NY, UK
| | - Kathrine Sofia Rallis
- Cancer Research Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
- Centre for Experimental Cancer Medicine, Barts Cancer Institute, Queen Mary University of London, London E1 4NS, UK
| | - Stergios Boussios
- Department of Medical Oncology, Medway NHS Foundation Trust, Gillingham ME7 5NY, UK
- Faculty of Life Sciences & Medicine, School of Cancer & Pharmaceutical Sciences, King’s College London, London WC2R 2LS, UK
- AELIA Organization, 9th Km Thessaloniki—Thermi, 57001 Thessaloniki, Greece
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49
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Bernstein-Molho R, Friedman E, Evron E. Controversies and Open Questions in Management of Cancer-Free Carriers of Germline Pathogenic Variants in BRCA1/BRCA2. Cancers (Basel) 2022; 14:cancers14194592. [PMID: 36230512 PMCID: PMC9559251 DOI: 10.3390/cancers14194592] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Revised: 09/06/2022] [Accepted: 09/19/2022] [Indexed: 11/16/2022] Open
Abstract
Females harboring germline BRCA1/BRCA2 (BRCA) P/LPV are offered a tight surveillance scheme from the age of 25−30 years, aimed at early detection of specific cancer types, in addition to risk-reducing strategies. Multiple national and international surveillance guidelines have been published and updated over the last two decades from geographically diverse countries. We searched for guidelines published between 1 January 2015 and 1 May 2022. Differences between guidelines on issues such as primary prevention, mammography screening in young (<30 years) carriers, MRI screening in carriers above age 65 years, breast imaging (if any) after risk-reducing bilateral mastectomy, during pregnancy, and breastfeeding, and hormone-replacement therapy, are just a few notable examples. Beyond formal guidelines, BRCA carriers’ concerns also focus on the timing of risk-reducing surgeries, fertility preservation, management of menopausal symptoms in cancer survivors, and pancreatic cancer surveillance, issues that, for some, there are no data to support evidence-based recommendations. This review discusses these unsettled issues, emphasizing the importance of future studies to enable global guideline harmonization for optimal surveillance strategies. Moreover, it raises the unmet need for personalized risk stratification and surveillance in BRCA P/LPV carriers.
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Affiliation(s)
- Rinat Bernstein-Molho
- The Oncogenetics Unit, Chaim Sheba Medical Center, Tel-Hashomer, The Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 5265601, Israel
| | - Eitan Friedman
- Assuta Medical Center, Tel-Aviv, Israel, The Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 8436322, Israel
| | - Ella Evron
- Oncology, Kaplan Medical Institute, Rehovot, Hadassah Medical School, The Hebrew University, Jerusalem 9190501, Israel
- Correspondence: or ; Tel.: +972-502-056-171
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Musanabaganwa C, Jansen S, Wani A, Rugamba A, Mutabaruka J, Rutembesa E, Uwineza A, Fatumo S, Hermans EJ, Souopgui J, Wildman DE, Uddin M, Roozendaal B, Njemini R, Mutesa L. Community engagement in epigenomic and neurocognitive research on post-traumatic stress disorder in Rwandans exposed to the 1994 genocide against the Tutsi: lessons learned. Epigenomics 2022; 14:887-895. [PMID: 36004496 PMCID: PMC9475497 DOI: 10.2217/epi-2022-0079] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Epigenomic and neurocognitive studies have provided new perspectives on post-traumatic stress disorder and its intergenerational transmission. This article outlines the lessons learned from community engagement (CE) in such research on Rwandan genocide survivors. A strong trauma-related response was observed within the research project-targeted community (genocide survivors) during explanation of the project. CE also revealed privacy concerns, as community members worried that any leakage of genetic/(epi)genomic data could affect not only themselves but also their close relatives. Adopting a culture of CE in the process of research implementation enables the prioritization of targeted community needs and interests. Furthermore, CE has stimulated the development of mental healthcare interventions, which married couples can apply to protect their offspring and thus truly break the cycle of inherited vulnerability.
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Affiliation(s)
- Clarisse Musanabaganwa
- Center for Human Genetics, College of Medicine & Health Sciences, University of Rwanda, Kigali, PO BOX 4285, Rwanda.,Department of Clinical Psychology, College of Medicine & Health Sciences, University of Rwanda, PO BOX 4285, Rwanda.,Genomics Program, College of Public Health, University of South Florida, FL 33612, USA.,Department of Cognitive Neuroscience, Radboud University Medical Center, 6500HB, Nijmegen, and Donders Institute for Brain, Cognition & Behaviour, Radboud University, Nijmegen, 6525EN, The Netherlands.,Frailty in Ageing Research Department, Vrije Universiteit Brussel, Jette Campus, 1090, Belgium
| | - Stefan Jansen
- Department of Clinical Psychology, College of Medicine & Health Sciences, University of Rwanda, PO BOX 4285, Rwanda.,Directorate of Research & Innovation, College of Medicine & Health Sciences, University of Rwanda, Kigali, PO-BOX 4285, Rwanda
| | - Agaz Wani
- Genomics Program, College of Public Health, University of South Florida, FL 33612, USA
| | - Alex Rugamba
- Center for Human Genetics, College of Medicine & Health Sciences, University of Rwanda, Kigali, PO BOX 4285, Rwanda
| | - Jean Mutabaruka
- Department of Clinical Psychology, College of Medicine & Health Sciences, University of Rwanda, PO BOX 4285, Rwanda
| | - Eugene Rutembesa
- Department of Clinical Psychology, College of Medicine & Health Sciences, University of Rwanda, PO BOX 4285, Rwanda
| | - Annette Uwineza
- Center for Human Genetics, College of Medicine & Health Sciences, University of Rwanda, Kigali, PO BOX 4285, Rwanda
| | - Segun Fatumo
- London School of Hygiene & Tropical Medicine, Bloomsbury, London, WC1E 7HT, UK.,The African Computational Genomics (TACG) Research Group, MRC/UVRI & LSHTM, Entebbe, 31302, Uganda
| | - Erno J Hermans
- Department of Cognitive Neuroscience, Radboud University Medical Center, 6500HB, Nijmegen, and Donders Institute for Brain, Cognition & Behaviour, Radboud University, Nijmegen, 6525EN, The Netherlands
| | - Jacob Souopgui
- Department of Molecular Biology, Institute of Biology & Molecular Medicine (IBMM), Université Libre de Bruxelles, Gosselies Campus, Gosselies, 126040, Belgium
| | - Derek E Wildman
- Genomics Program, College of Public Health, University of South Florida, FL 33612, USA
| | - Monica Uddin
- Genomics Program, College of Public Health, University of South Florida, FL 33612, USA
| | - Benno Roozendaal
- Department of Cognitive Neuroscience, Radboud University Medical Center, 6500HB, Nijmegen, and Donders Institute for Brain, Cognition & Behaviour, Radboud University, Nijmegen, 6525EN, The Netherlands
| | - Rose Njemini
- Frailty in Ageing Research Department, Vrije Universiteit Brussel, Jette Campus, 1090, Belgium
| | - Leon Mutesa
- Center for Human Genetics, College of Medicine & Health Sciences, University of Rwanda, Kigali, PO BOX 4285, Rwanda
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