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Poorolajal J, Doosti-Irani A, Karami AM, Fattahi-Darghlou M. A dose-response meta-analysis of the relationship between number of pregnancies and risk of gynecological cancers. Arch Gynecol Obstet 2024; 310:2783-2790. [PMID: 39397087 DOI: 10.1007/s00404-024-07774-x] [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: 03/29/2024] [Accepted: 10/05/2024] [Indexed: 10/15/2024]
Abstract
BACKGROUND Despite several investigations, the association between the number of pregnancies and gynecological cancers remains inconclusive. To address this issue, we conducted a dose-response meta-analysis of observational studies. METHODS We searched PubMed, Web of Science, and Scopus databases up to Jun 8, 2023, to identify observational studies that examined the association between the number of pregnancies and gynecologic cancers. To assess the heterogeneity across studies, we used the χ2 test and I2 statistics. We also explored the possibility of publication bias using Begg's and Egger's tests. The overall effect sizes were reported as odds ratios (ORs) with a 95% confidence interval (CI) using a random-effects model. RESULTS Out of the 87,255 studies initially identified, a total of 101 studies involving 8,230,754 participants were included in the final meta-analysis. Our analysis revealed a positive trend between the number of pregnancies and cervical cancer; however, this association was not found to be statistically significant except for fifth pregnancy. Conversely, our findings showed a significant decreasing trend between the number of pregnancies and the risk of endometrial and ovarian cancers. There was insufficient evidence to establish a relationship between the number of pregnancies and the risk of vaginal, vulvar, and fallopian tube cancers. CONCLUSIONS Our study found a positive trend between the number of pregnancies and cervical cancer and a significant decreasing trend between the number of pregnancies and endometrial and ovarian cancers. These findings may have implications for counseling women about their reproductive health and the potential risks and benefits of pregnancy.
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Affiliation(s)
- Jalal Poorolajal
- Department of Epidemiology, School of Public Health, Hamadan University of Medical Sciences, Hamadan, Iran
- Modeling of Noncommunicable Diseases Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
- Research Center for Health Sciences, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Amin Doosti-Irani
- Department of Epidemiology, School of Public Health, Hamadan University of Medical Sciences, Hamadan, Iran
- Research Center for Health Sciences, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Ali Mohammad Karami
- Department of Epidemiology, School of Public Health, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Marzieh Fattahi-Darghlou
- Department of Epidemiology, School of Public Health, Hamadan University of Medical Sciences, Hamadan, Iran.
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Jahanfar S, Mortazavi J, Lapidow A, Cu C, Al Abosy J, Morris K, Becerra-Mateus JC, Steinfeldt M, Maurer O, Bohang J, Andrenacci P, Badawy M, Ali M. Assessing the impact of contraceptive use on reproductive cancer risk among women of reproductive age-a systematic review. Front Glob Womens Health 2024; 5:1487820. [PMID: 39606555 PMCID: PMC11599208 DOI: 10.3389/fgwh.2024.1487820] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Accepted: 10/24/2024] [Indexed: 11/29/2024] Open
Abstract
Background Contraceptives play a crucial role in women's reproductive health, their hormonal components may be linked to cancer risks, specifically breast, and gynecological cancers. Given the high usage rates of hormonal contraceptives, it is vital to systematically evaluate their potential impact on cancer outcomes, especially among women with a family history of gynecological cancers. Objectives This study aims to evaluate the evidence on the association between modern contraceptive use and the risk of breast and reproductive cancers (ovarian, endometrial, and cervical cancer) among women of reproductive age, to inform healthcare providers, women, and program managers about cancer outcomes related to contraceptive use. Methods A systematic review was conducted according to PRISMA guidelines. Searches were performed in databases such as CINAHL, OVID Medline, EMBASE, and more from inception to February 2022. Eligible studies included randomized controlled trials, cohort studies, and case-control studies that compared cancer outcomes between contraceptive users and non-users. Data extraction, quality assessment, and meta-analyses were conducted following predefined protocols. Subgroup and sensitivity analyses examined variations in contraceptive methods, doses, and duration. Results A total of 51 studies were included, comprising 2 RCTs and 49 observational studies. The review identified a significant reduction in ovarian and endometrial cancer incidence among contraceptive users. Hormonal contraceptive users had a 36% lower risk of ovarian cancer (RR 0.64, 95% CI 0.60-0.68), with specific reductions seen in combined oral contraceptive users (RR 0.62, 95% CI 0.57-0.68) and hormonal IUD users (RR 0.68, 95% CI 0.48-0.96). The rate ratio of cervical cancer was higher among non- users compared to hormonal contraceptive users when we pooled the results (1.28, 95% CI 1.21, 1.35). No significant association was found between contraceptive use and breast cancer risk among healthy women (RR 1.00, 95% CI 0.94-1.06). However, BRCA1/2 mutation carriers using oral contraceptives showed a heightened risk of breast cancer (HR 1.39, 95% CI 1.15-1.67). Conclusion This systematic review highlights the protective effects of modern contraceptives against ovarian and endometrial cancers while identifying an increased risk of cervical. No significant breast cancer risk was found for healthy women, but BRCA1/2 mutation carriers faced increased risks. These findings underscore the need for personalized contraceptive counselling that considers cancer risk factors. Further research is needed to explore contraceptive impacts across different genetic profiles and dosing regimens. Systematic Review Registration https://www.crd.york.ac.uk/prospero/, Prospero (CRD42022332647).
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Affiliation(s)
- Shayesteh Jahanfar
- Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, MA, United States
| | - Julie Mortazavi
- Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, MA, United States
| | - Amy Lapidow
- Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, MA, United States
| | - Cassandra Cu
- Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, MA, United States
- School of Medicine, Tufts University School of Medicine, Boston, MA, United States
| | - Jude Al Abosy
- Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, MA, United States
| | - Kathyrn Morris
- Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, MA, United States
| | | | - Meredith Steinfeldt
- Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, MA, United States
| | - Olivia Maurer
- Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, MA, United States
| | - Jiang Bohang
- Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, MA, United States
| | | | | | - Moazzam Ali
- WHO Department of Sexual and Reproductive Health and Research, World Health Organization, Geneva, Switzerland
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Gersekowski K, Na R, Alsop K, Delahunty R, Goode EL, Cunningham JM, Winham SJ, Pharoah PD, Song H, Webb PM. Risk Factors for Ovarian Cancer by BRCA Status: A Collaborative Case-Only Analysis. Cancer Epidemiol Biomarkers Prev 2024; 33:586-592. [PMID: 38300121 PMCID: PMC11268497 DOI: 10.1158/1055-9965.epi-23-0984] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Revised: 11/20/2023] [Accepted: 01/30/2024] [Indexed: 02/02/2024] Open
Abstract
BACKGROUND Women with an inherited pathogenic variant in BRCA1 or BRCA2 have a greatly increased risk of developing ovarian cancer, but the importance of behavioral factors is less clear. We used a case-only design to compare the magnitude of associations with established reproductive, hormonal, and lifestyle risk factors between BRCA mutation carriers and noncarriers. METHODS We pooled data from five studies from the Ovarian Cancer Association Consortium including 637 BRCA carriers and 4,289 noncarriers. Covariate-adjusted generalized linear mixed models were used to estimate interaction risk ratios (IRR) and 95% confidence intervals (CI), with BRCA (carrier vs. noncarrier) as the response variable. RESULTS IRRs were above 1.0 for known protective factors including ever being pregnant (IRR = 1.29, 95% CI; 1.00-1.67) and ever using the oral contraceptive pill (1.30, 95% CI; 1.07-1.60), suggesting the protective effects of these factors may be reduced in carriers compared with noncarriers. Conversely, the IRRs for risk factors including endometriosis and menopausal hormone therapy were below 1.0, suggesting weaker positive associations among BRCA carriers. In contrast, associations with lifestyle factors including smoking, physical inactivity, body mass index, and aspirin use did not appear to differ by BRCA status. CONCLUSIONS Our results suggest that associations with hormonal and reproductive factors are generally weaker for those with a pathogenic BRCA variant than those without, while associations with modifiable lifestyle factors are similar for carriers and noncarriers. IMPACT Advice to maintain a healthy weight, be physically active, and refrain from smoking will therefore benefit BRCA carriers as well as noncarriers.
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Affiliation(s)
- Kate Gersekowski
- Population Health Program, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia
| | - Renhua Na
- Population Health Program, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia
- University of Queensland, School of Public Health, Brisbane, Queensland, Australia
| | - Kathryn Alsop
- Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
- Sir Peter MacCallum Department of Oncology, The University of Melbourne, Victoria, Australia
| | - Rachel Delahunty
- Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
- Sir Peter MacCallum Department of Oncology, The University of Melbourne, Victoria, Australia
| | - Ellen L. Goode
- Division of Epidemiology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota
| | - Julie M. Cunningham
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
| | - Stacey J. Winham
- Division of Computational Biology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota
| | - Paul D.P. Pharoah
- Department of Computational Biomedicine, Cedars-Sinai Medical Center, West Hollywood, California
- Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, United Kingdom
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
| | - Honglin Song
- Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
| | - Penelope M. Webb
- Population Health Program, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia
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Kojima R, Toyoshima M, Yamamoto A, Suzuki S. Preoperative screening endometrial cytology discovered incidental gynaecological malignancy in two patients undergoing risk-reducing salpingo-oophorectomy. BMJ Case Rep 2023; 16:e254484. [PMID: 36918214 PMCID: PMC10016279 DOI: 10.1136/bcr-2022-254484] [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] [Accepted: 03/02/2023] [Indexed: 03/16/2023] Open
Abstract
Pelvic ultrasonography and measurement of serum cancer antigen 125 (CA-125) are recommended for preoperative evaluation before performing risk-reducing salpingo-oophorectomy (RRSO). We report our experience with two patients in whom an incidental gynaecological malignancy was found using endometrial cytology as a preoperative screening test for RRSO. Patient 1 was an early 50s woman with a pathologic variant of BRCA1 Transvaginal ultrasonography showed no endometrial abnormalities, but preoperative endometrial cytology revealed high-grade serous carcinoma. The patient underwent total hysterectomy, bilateral adnexectomy, pelvic and para-aortic lymph node dissection, and omentectomy. Patient 2 was a late 40s woman with a pathological variant of BRCA1 Transvaginal ultrasonography showed mild enlargement of the left ovary, and her CA-125 level was elevated. Preoperative endometrial cytology revealed high-grade serous cancer. She underwent total hysterectomy, bilateral adnexectomy and omentectomy. These case reports illustrate the importance of preoperative screening-including endometrial cytology-before performing RRSO.
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Affiliation(s)
- Riho Kojima
- OB-GY, Nippon Medical School, Bunkyo-ku, Tokyo, Japan
| | | | | | - Shunji Suzuki
- OB-GY, Nippon Medical School, Bunkyo-ku, Tokyo, Japan
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van Bommel MHD, IntHout J, Veldmate G, Kets CM, de Hullu JA, van Altena AM, Harmsen MG. Contraceptives and cancer risks in BRCA1/2 pathogenic variant carriers: a systematic review and meta-analysis. Hum Reprod Update 2023; 29:197-217. [PMID: 36383189 PMCID: PMC9976973 DOI: 10.1093/humupd/dmac038] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Revised: 09/20/2022] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND Increasing numbers of BReast CAncer (BRCA) 1 or 2 pathogenic variant (PV) carriers, who have an inherited predisposition to breast and ovarian cancer, are being identified. Among these women, data regarding the effects of contraception on cancer risks are unclear and various guidelines provide various recommendations. OBJECTIVE AND RATIONALE We aim to optimize counselling regarding contraception for BRCA1/2-PV carriers. Therefore, we performed a systematic review and meta-analysis. We investigated the risk ratio for developing breast cancer or ovarian cancer in BRCA1/2-PV carriers who have used any form of contraception versus non-users. Second, we analysed breast and ovarian cancer risk among BRCA1/2-PV carriers as influenced by the duration of contraceptive use and by the time since last use. In addition, we provide an overview of all relevant international guidelines regarding contraceptive use for BRCA1/2-PV carriers. SEARCH METHODS A systematic search in the Medline database and Cochrane library identified studies describing breast and/or ovarian cancer risk in BRCA1/2-PV carriers as modified by contraception until June 2021. The search included medical subject headings, keywords and synonyms related to BRCA and contraceptives (any kind). PRISMA guidance was followed. Risk Of Bias In Non-randomized Studies of Interventions and Grading of Recommendations, Assessment, Development and Evaluations assessments were performed. Random-effects meta-analyses were used to estimate pooled effects for breast and ovarian cancer risk separately. Subgroup analyses were conducted for BRCA1 versus BRCA2 and for the various contraceptive methods. OUTCOMES Results of the breast cancer risk with oral contraceptive pill (OCP) analysis depended on the outcome measure. Meta-analyses of seven studies with 7525 women revealed a hazard ratio (HR) of 1.55 (95% CI: 1.36-1.76) and of four studies including 9106 women resulted in an odds ratio (OR) of 1.06 (95% CI: 0.90-1.25), heterogeneity (I2) 0% and 52%, respectively. Breast cancer risk was still increased in ever-users compared with never-users >10 years after last OCP use. In contrast, ovarian cancer risk was decreased among OCP users: HR 0.62 (95% CI: 0.52-0.74) based on two studies including 10 981 women (I2: 0%), and OR 0.49 (95% CI: 0.38-0.63) based on eight studies including 10 390 women (I2: 64%). The protective effect vanished after cessation of use. Tubal ligation also protects against ovarian cancer: one study including 3319 women (I2: 0%): HR: 0.44 (95% CI: 0.26-0.74) and three studies with 7691 women (I2: 44%): OR: 0.74 (95% CI: 0.53-1.03). Data regarding other contraceptives were unavailable. No differences were observed between BRCA1 and BRCA2-PV carriers. The quality of evidence was either low or very low. WIDER IMPLICATIONS The OCP potentially increases breast cancer risk, while ovarian cancer risk decreases with either the OCP and tubal ligation in BRCA1/2-PV carriers. Counselling of BRCA1/2-PV carriers should be personalized; the genetic and non-genetic factors (like prior risk-reducing surgeries, prior breast cancer and age) and patients' preferences (reversibility, ease of use, reliability and effect on menstrual cycle) should be balanced. To further optimize counselling for high-risk women, future research should focus on other (commonly used) contraceptive methods and cancer risks in this specific population, and on the potential impact of changing formulations over time.
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Affiliation(s)
- Majke H D van Bommel
- Department of Obstetrics and Gynaecology, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, the Netherlands
| | - Joanna IntHout
- Department for Health Evidence, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, the Netherlands
| | - Guus Veldmate
- Department of Obstetrics and Gynaecology, Gelderse Vallei Hospital, Ede, the Netherlands
| | - C Marleen Kets
- Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Joanne A de Hullu
- Department of Obstetrics and Gynaecology, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, the Netherlands
| | - Anne M van Altena
- Department of Obstetrics and Gynaecology, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, the Netherlands
| | - Marline G Harmsen
- Department of Obstetrics and Gynaecology, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, the Netherlands
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Barańska A, Kanadys W. Oral Contraceptive Use and Breast Cancer Risk for BRCA1 and BRCA2 Mutation Carriers: Systematic Review and Meta-Analysis of Case–Control Studies. Cancers (Basel) 2022; 14:cancers14194774. [PMID: 36230696 PMCID: PMC9564239 DOI: 10.3390/cancers14194774] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2022] [Revised: 09/15/2022] [Accepted: 09/25/2022] [Indexed: 11/16/2022] Open
Abstract
Oral contraceptive use is one of the major modifiable risk factors for breast cancer. To investigate the effect of oral contraceptive taking on breast cancer risk by BRCA 1 and BRCA 2 mutation status, we conducted a systematic review and meta-analysis of case-controlled studies. Therefore, English language articles were retrieved by searching MEDLINE (PubMed), EMBASE and the Cochrane Library up to August 2021. Data were pooled from none case–control studies, comprising a total of 33,162 subjects, including 23,453 who had never used oral contraceptives. Overall meta-analysis indicated a statistically insignificant risk reduction: OR = 0.86, 95% CI: 0.70 to 1.06, p = 0.1594. However, increased breast cancer risk was associated with age at first use of OCs ≥20 years: OR = 1.21, 95% CI:1.07 to 1.36, p = 0.002. Multivariable meta-regression with covariates of age of first OC use (β = 0.21, 95% CI: −0.25 to 0.67, p = 0.3767), duration of OC use (β = −0.08, 95% CI; −0.51 to 0.34, p = 0.7093), and time since last OC use (β = 0.32, 95% CI: −0.22 to 0.85, p = 0.2461) did not have a significant effect on the breast cancer risk. This meta-analysis suggests a diverse effect of oral contraceptive use against breast cancer in BRCA carrier mutation. The association between OC use and breast and ovarian cancers needs more investigation.
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Affiliation(s)
- Agnieszka Barańska
- Department of Medical Informatics and Statistics with E-Learning Lab, Medical University of Lublin, 20-954 Lublin, Poland
- Correspondence:
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Park KJ, Broach V, Chi DS, Linkov I, Stanczyk FZ, Patel P, Jotwani A, Pearce CL, Pike MC, Kauff ND. Proliferation of the Fallopian Tube Fimbriae and Cortical Inclusion Cysts: Effects of the Menstrual Cycle and the Levonorgestrel Intrauterine Contraceptive System. Cancer Epidemiol Biomarkers Prev 2022; 31:1823-1829. [PMID: 35700017 PMCID: PMC9444882 DOI: 10.1158/1055-9965.epi-22-0217] [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: 02/27/2022] [Revised: 05/03/2022] [Accepted: 06/09/2022] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND The objectives of this study were (i) to explore whether differences in cell proliferation may help explain why most high-grade serous ovarian cancers (HGSOC) arise in the fallopian tube fimbriae (FTF) rather than in ovarian cortical inclusion cysts (CIC); (ii) to compare premenopausal and postmenopausal FTF proliferation as a reason why the age incidence of HGSOC increases at a slower rate after menopause; and (iii) to compare FTF proliferation in cycling women and women using the levonorgestrel intrauterine contraceptive system (Lng-IUS) to see whether proliferation on the Lng-IUS was lower. METHODS We studied 60 women undergoing a salpingo-oophorectomy. We used Ki67, paired-box gene 8 (PAX8, Müllerian marker), and calretinin (mesothelial marker) to study FTF and CIC proliferation. RESULTS FTF Ki67%+ was greater in the follicular than in the luteal phase (4.9% vs. 1.5%; P = 0.003); postmenopausal Ki67%+ was 1.7%. Ki67%+ in PAX8 negative (PAX8-) CICs was extremely low. Proliferation in PAX8+ CICs did not vary by menstrual phase or menopausal status. Follicular Ki67%+ was 2.6-fold higher in FTF than PAX8+ CICs. FTF Ki67%+ from 10 women using the Lng-IUS was not lower than in cycling women. CONCLUSIONS Overall FTF Ki67%+ is greater than overall CIC Ki67%+. Overall FTF Ki67%+ in postmenopausal women is lower than in premenopausal women. The Lng-IUS is not associated with lower FTF Ki67%+. IMPACT Ki67%+ provides an explanation of the preponderance of FTF-derived HGSOCs, and of the slower increase of HGSOCs after menopause. The Lng-IUS may not be associated with a protective effect against HGSOCs.
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Affiliation(s)
- Kay J. Park
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Vance Broach
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Dennis S. Chi
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Irina Linkov
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Frank Z Stanczyk
- Departments of Obstetrics and Gynecology and Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, California
| | - Prusha Patel
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Anjali Jotwani
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Celeste Leigh Pearce
- Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, Michigan
| | - Malcolm C. Pike
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Noah D. Kauff
- Division of Cancer Genetics, Northwell Health Cancer Institute, Lake Success, New York, New York
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Lee A, Yang X, Tyrer J, Gentry-Maharaj A, Ryan A, Mavaddat N, Cunningham AP, Carver T, Archer S, Leslie G, Kalsi J, Gaba F, Manchanda R, Gayther S, Ramus SJ, Walter FM, Tischkowitz M, Jacobs I, Menon U, Easton DF, Pharoah P, Antoniou AC. Comprehensive epithelial tubo-ovarian cancer risk prediction model incorporating genetic and epidemiological risk factors. J Med Genet 2022; 59:632-643. [PMID: 34844974 PMCID: PMC9252860 DOI: 10.1136/jmedgenet-2021-107904] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Accepted: 05/18/2021] [Indexed: 12/31/2022]
Abstract
BACKGROUND Epithelial tubo-ovarian cancer (EOC) has high mortality partly due to late diagnosis. Prevention is available but may be associated with adverse effects. A multifactorial risk model based on known genetic and epidemiological risk factors (RFs) for EOC can help identify women at higher risk who could benefit from targeted screening and prevention. METHODS We developed a multifactorial EOC risk model for women of European ancestry incorporating the effects of pathogenic variants (PVs) in BRCA1, BRCA2, RAD51C, RAD51D and BRIP1, a Polygenic Risk Score (PRS) of arbitrary size, the effects of RFs and explicit family history (FH) using a synthetic model approach. The PRS, PV and RFs were assumed to act multiplicatively. RESULTS Based on a currently available PRS for EOC that explains 5% of the EOC polygenic variance, the estimated lifetime risks under the multifactorial model in the general population vary from 0.5% to 4.6% for the first to 99th percentiles of the EOC risk distribution. The corresponding range for women with an affected first-degree relative is 1.9%-10.3%. Based on the combined risk distribution, 33% of RAD51D PV carriers are expected to have a lifetime EOC risk of less than 10%. RFs provided the widest distribution, followed by the PRS. In an independent partial model validation, absolute and relative 5-year risks were well calibrated in quintiles of predicted risk. CONCLUSION This multifactorial risk model can facilitate stratification, in particular among women with FH of cancer and/or moderate-risk and high-risk PVs. The model is available via the CanRisk Tool (www.canrisk.org).
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Affiliation(s)
- Andrew Lee
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
| | - Xin Yang
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
| | - Jonathan Tyrer
- Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK
| | - Aleksandra Gentry-Maharaj
- MRC Clinical Trials Unit, Institute of Clinical Trials & Methodology, University College London, London, UK
| | - Andy Ryan
- MRC Clinical Trials Unit, Institute of Clinical Trials & Methodology, University College London, London, UK
| | - Nasim Mavaddat
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
| | - Alex P Cunningham
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
| | - Tim Carver
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
| | - Stephanie Archer
- The Primary Care Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
| | - Goska Leslie
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
| | - Jatinder Kalsi
- Department of Women's Cancer, University College London Institute for Women's Health, London, UK
- Department of Epidemiology and Public Health, University College London Research, London, UK
| | - Faiza Gaba
- CRUK Barts Cancer Centre, Wolfson Institute of Preventive Medicine, London, UK
| | - Ranjit Manchanda
- CRUK Barts Cancer Centre, Wolfson Institute of Preventive Medicine, London, UK
- Department of Gynaecological Oncology, Barts Health NHS Trust, London, UK
- Department of Health Services Research, London School of Hygiene & Tropical Medicine, London, UK
| | - Simon Gayther
- Center for Bioinformatics and Functional Genomics, Cedars-Sinai Medical Center Samuel Oschin Comprehensive Cancer Institute, Los Angeles, California, USA
| | - Susan J Ramus
- University of New South Wales, School of Women's and Children's Health, Randwick, New South Wales, Australia
- Adult Cancer Program, Lowy Cancer Research Centre, University of New South Wales, Sydney, New South Wales, Australia
| | - Fiona M Walter
- The Primary Care Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
| | - Marc Tischkowitz
- Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, University of Cambridge, Cambridge, UK
| | - Ian Jacobs
- Department of Women's Cancer, University College London Institute for Women's Health, London, UK
- University of New South Wales, School of Women's and Children's Health, Randwick, New South Wales, Australia
| | - Usha Menon
- MRC Clinical Trials Unit, Institute of Clinical Trials & Methodology, University College London, London, UK
| | - Douglas F Easton
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
- Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK
| | - Paul Pharoah
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
- Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK
| | - Antonis C Antoniou
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
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9
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Xia YY, Kotsopoulos J. Beyond the pill: contraception and the prevention of hereditary ovarian cancer. Hered Cancer Clin Pract 2022; 20:21. [PMID: 35668475 PMCID: PMC9169328 DOI: 10.1186/s13053-022-00227-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Accepted: 05/05/2022] [Indexed: 12/04/2022] Open
Abstract
BRCA1 and BRCA2 mutation carriers face an elevated lifetime risk of developing ovarian cancer. Oral contraceptives have been shown to significantly decrease the risk of ovarian cancer by approximately 50% in this high-risk population. Changes in contraceptive formulations and patterns of use over time have introduced lower hormonal dosages, different steroid types and non-oral routes of administration. Specifically, there has been a considerable shift in patterns of contraceptive use and the increase in the uptake of non-oral, long-acting, reversible contraception (e.g., intrauterine devices, implants, injections) has corresponded to a decline in oral contraceptive pill use. Whether or not these other methods confer a protective effect against ovarian cancer in the general population is not clear. To our knowledge, there have been no such studies conducted among BRCA mutation carriers. Furthermore, the impact of these changes on the risk of developing ovarian cancer is not known. In this article, we will review the existing epidemiologic evidence regarding the role of contraceptives and the risk of ovarian cancer with a focus on women with a BRCA1 or BRCA2 mutation. We will discuss recent findings and gaps in the knowledge while extrapolating from studies conducted among women from the noncarrier population.
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Affiliation(s)
- Yue Yin Xia
- Women's College Research Institute, Women's College Hospital, 76 Grenville Street, 6th Floor, Toronto, ON, M5S 1B2, Canada
- Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada
| | - Joanne Kotsopoulos
- Women's College Research Institute, Women's College Hospital, 76 Grenville Street, 6th Floor, Toronto, ON, M5S 1B2, Canada.
- Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
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Park J, Huang D, Chang YJ, Lim MC, Myung SK. Oral contraceptives and risk of breast cancer and ovarian cancer in women with a BRCA1 or BRCA2 mutation: A meta-analysis of observational studies. Carcinogenesis 2021; 43:231-242. [PMID: 34958358 DOI: 10.1093/carcin/bgab107] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 10/10/2021] [Accepted: 11/01/2021] [Indexed: 11/14/2022] Open
Abstract
It remains inconclusive whether the use of oral contraceptives (OCs) alters the risks of breast or ovarian cancer in women with a BRCA1 or BRCA2 mutation. We investigated the association between OC use and the risks of breast or ovarian cancer in this group by using a meta-analysis. PubMed and EMBASE were searched using keywords until February 2021 to identify relevant studies that evaluated the association between OC ever use and the risks of breast or ovarian cancer in women with a BRCA1 or BRCA2 mutation. Twelve studies for breast cancer and eight studies for ovarian cancer were identified. In the random-effects meta-analysis, the ever use of OCs was significantly associated with an increased risk of breast cancer [odds ratio (OR), relative risk (RR), or hazard ration (HR) = 1.24; 95% confidence interval (CI) 1.08 - 1.41] and a decreased risk of ovarian cancer (OR/RR/HR = 0.53, 95% CI 0.41 - 0.67). Consistent findings were observed, when BRCA1 and BRCA2 mutation carriers were analyzed separately. The increased risk of breast cancer was observed only in the long-term (>5 years) users of OCs, while the decrease risk of ovarian cancer was observed regardless of the duration of OC use. The current study suggests that the ever use of OCs in BRCA mutation carriers is significantly associated with an increased risk of breast cancer and a decreased risk of ovarian cancer. Therefore, the use of OCs as chemoprevention of ovarian cancer should be cautious in BRCA mutation carriers.
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Affiliation(s)
- Junli Park
- Center for Cancer Prevention and Detection, Hospital, National Cancer Center, Goyang, Korea.,Department of Family Medicine, Myongji Hospital, Goyang, Korea
| | - Dan Huang
- Division of Cancer Control & Policy, National Cancer Control Institute, National Cancer Center, Goyang, Korea.,Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Yoon Jung Chang
- Division of Cancer Control & Policy, National Cancer Control Institute, National Cancer Center, Goyang, Korea.,Department of Cancer Control and Population Health, National Cancer Center Graduate School of Cancer Science and Policy, Goyang, Korea.,Department of Family Medicine, Hospital, National Cancer Center, Goyang, Korea
| | - Myong Cheol Lim
- Department of Cancer Control and Population Health, National Cancer Center Graduate School of Cancer Science and Policy, Goyang, Korea.,Center for Gynecologic Cancer, Hospital, National Cancer Center, Goyang, Korea.,Division of Tumor Immunology, Research Institute, National Cancer Center, Goyang, Korea
| | - Seung-Kwon Myung
- Department of Family Medicine, Hospital, National Cancer Center, Goyang, Korea.,Department of Cancer Biomedical Science, National Cancer Center Graduate School of Cancer Science and Policy, Goyang, Korea.,Division of Cancer Epidemiology and Management, Research Institute, National Cancer Center, Goyang, Korea
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11
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Eoh KJ, Park EY, Chang YJ, Ha HI, Hong J, Huang D, Nam EJ, Lim MC. The preventive effect of breastfeeding against ovarian cancer in BRCA1 and BRCA2 mutation carriers: A systematic review and meta-analysis. Gynecol Oncol 2021; 163:142-147. [PMID: 34304906 DOI: 10.1016/j.ygyno.2021.07.028] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2021] [Revised: 07/02/2021] [Accepted: 07/15/2021] [Indexed: 10/20/2022]
Abstract
OBJECTIVE A recent study showed that even a few months of breastfeeding is associated with a significant decrease in the risk of ovarian cancer in the general population. This study aimed to perform a systematic review and meta-analysis to determine the significance of the length of the breastfeeding period on ovarian cancer risk in BRCA1/2 mutation carriers. METHODS PubMed, EMBASE, and Cochrane databases were searched up to June 1, 2021. We included case-control and cohort studies that contained information on breastfeeding and the risk of ovarian cancer in BRCA1/2 mutation carriers. Odds ratios (OR) were meta-analytically pooled using a fixed-effects model.dd RESULTS: Five studies, including one cohort study and four case-control studies, were included in this meta-analysis. Of the 14,601 BRCA1/2 mutation carriers, the overall pooled OR of ever having performed breastfeeding in patients who had ovarian cancer was 0.767 (95% confidence interval [CI], 0.688-0.856) and 0.817 (95% CI, 0.650-1.028) for patients with BRCA1 and BRCA2 mutation, respectively. Breastfeeding for >1 year acted as a protective factor in both BRCA1 [OR: 0.787 (95% CI, 0.682-0.907)] and BRCA2 [OR: 0.567 (95% CI, 0.400-0.802)] mutation carriers. No significant heterogeneity was present (I2 = 0%), and the funnel plot was also properly distributed, showing no publication bias. CONCLUSIONS Breastfeeding is a preventive, modifiable factor for ovarian cancer in BRCA1/2 mutation carriers. Ever having performed breastfeeding was significantly preventive for ovarian cancer in the BRCA1 mutation carriers, however a period of 1 year or more of breastfeeding is required for a reduced ovarian cancer risk in BRCA2 mutation carriers.
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Affiliation(s)
- Kyung Jin Eoh
- Department of Obstetrics and Gynecology, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Republic of Korea
| | - Eun Young Park
- Biostatistics Collaboration Team, Research Core Center, National Cancer Center, Goyang, Republic of Korea; Department of Statistics and Data Science, College of Commerce and Economics, Yonsei University, Seoul, Republic of Korea
| | - Yoon Jung Chang
- Department of Cancer Control and Population Health, National Cancer Center Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Republic of Korea; Division of Cancer Control and Policy, National Cancer Control Institute, National Cancer Center, Goyang, Republic of Korea
| | - Hyeong In Ha
- Department of Obstetrics and Gynecology, Pusan National University Yangsan Hospital, Pusan National school of medicine, Yangsan, Republic of Korea
| | - Juhye Hong
- Division of Cancer Control and Policy, National Cancer Control Institute, National Cancer Center, Goyang, Republic of Korea
| | - Dan Huang
- Division of Cancer Control and Policy, National Cancer Control Institute, National Cancer Center, Goyang, Republic of Korea
| | - Eun Ji Nam
- Department of Obstetrics and Gynecology, Institute of Women's Medical Life Science, Yonsei Cancer Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Myong Cheol Lim
- Department of Cancer Control and Population Health, National Cancer Center Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Republic of Korea; Division of Tumor Immunology and Center for Gynecologic Cancer, Research Institute and Hospital, Goyang, Republic of Korea.
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12
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Schrijver LH, Antoniou AC, Olsson H, Mooij TM, Roos-Blom MJ, Azarang L, Adlard J, Ahmed M, Barrowdale D, Davidson R, Donaldson A, Eeles R, Evans DG, Frost D, Henderson A, Izatt L, Ong KR, Bonadona V, Coupier I, Faivre L, Fricker JP, Gesta P, van Engelen K, Jager A, Menko FH, Mourits MJE, Singer CF, Tan YY, Foretova L, Navratilova M, Schmutzler RK, Ellberg C, Gerdes AM, Caldes T, Simard J, Olah E, Jakubowska A, Rantala J, Osorio A, Hopper JL, Phillips KA, Milne RL, Beth Terry M, Noguès C, Engel C, Kast K, Goldgar DE, van Leeuwen FE, Easton DF, Andrieu N, Rookus MA. Oral contraceptive use and ovarian cancer risk for BRCA1/2 mutation carriers: an international cohort study. Am J Obstet Gynecol 2021; 225:51.e1-51.e17. [PMID: 33493488 PMCID: PMC8278569 DOI: 10.1016/j.ajog.2021.01.014] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Revised: 10/30/2020] [Accepted: 01/19/2021] [Indexed: 01/24/2023]
Abstract
BACKGROUND Ovarian cancer risk in BRCA1 and BRCA2 mutation carriers has been shown to decrease with longer duration of oral contraceptive use. Although the effects of using oral contraceptives in the general population are well established (approximately 50% risk reduction in ovarian cancer), the estimated risk reduction in mutation carriers is much less precise because of potential bias and small sample sizes. In addition, only a few studies on oral contraceptive use have examined the associations of duration of use, time since last use, starting age, and calendar year of start with risk of ovarian cancer. OBJECTIVE This study aimed to investigate in more detail the associations of various characteristics of oral contraceptive use and risk of ovarian cancer, to provide healthcare providers and carriers with better risk estimates. STUDY DESIGN In this international retrospective study, ovarian cancer risk associations were assessed using oral contraceptives data on 3989 BRCA1 and 2445 BRCA2 mutation carriers. Age-dependent-weighted Cox regression analyses were stratified by study and birth cohort and included breast cancer diagnosis as a covariate. To minimize survival bias, analyses were left truncated at 5 years before baseline questionnaire. Separate analyses were conducted for each aspect of oral contraceptive use and in a multivariate analysis, including all these aspects. In addition, the analysis of duration of oral contraceptive use was stratified by recency of use. RESULTS Oral contraceptives were less often used by mutation carriers who were diagnosed with ovarian cancer (ever use: 58.6% for BRCA1 and 53.5% BRCA2) than by unaffected carriers (ever use: 88.9% for BRCA1 and 80.7% for BRCA2). The median duration of use was 7 years for both BRCA1 and BRCA2 carriers who developed ovarian cancer and 9 and 8 years for unaffected BRCA1 and BRCA2 carriers with ovarian cancer, respectively. For BRCA1 mutation carriers, univariate analyses have shown that both a longer duration of oral contraceptive use and more recent oral contraceptive use were associated with a reduction in the risk of ovarian cancer. However, in multivariate analyses, including duration of use, age at first use, and time since last use, duration of oral contraceptive use proved to be the prominent protective factor (compared with <5 years: 5-9 years [hazard ratio, 0.67; 95% confidence interval, 0.40-1.12]; >10 years [hazard ratio, 0.37; 95% confidence interval, 0.19-0.73]; Ptrend=.008). The inverse association between duration of use and ovarian cancer risk persisted for more than 15 years (duration of ≥10 years; BRCA1 <15 years since last use [hazard ratio, 0.24; 95% confidence interval, 0.14-0.43]; BRCA1 >15 years since last use [hazard ratio, 0.56; 95% confidence interval, 0.18-0.59]). Univariate results for BRCA2 mutation carriers were similar but were inconclusive because of limited sample size. CONCLUSION For BRCA1 mutation carriers, longer duration of oral contraceptive use is associated with a greater reduction in ovarian cancer risk, and the protection is long term.
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Affiliation(s)
- Lieske H Schrijver
- Department of Epidemiology, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Antonis C Antoniou
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
| | - Håkan Olsson
- Department of Oncology, Lund University Hospital, Lund, Sweden
| | - Thea M Mooij
- Department of Epidemiology, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Marie-José Roos-Blom
- Department of Epidemiology, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Leyla Azarang
- Department of Epidemiology, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Julian Adlard
- Yorkshire Regional Genetics Service, Chapel Allerton Hospital, Leeds, United Kingdom
| | - Munaza Ahmed
- North East Thames Regional Genetics Service, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom
| | - Daniel Barrowdale
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
| | - Rosemarie Davidson
- Department of Clinical Genetics, South Glasgow University Hospitals, Glasgow, United Kingdom
| | - Alan Donaldson
- Department of Clinical Genetics, St. Michael's Hospital, Bristol, United Kingdom
| | - Ros Eeles
- Oncogenetics Team, The Institute of Cancer Research, London, United Kingdom
| | - D Gareth Evans
- Division of Evolution and Genomic Sciences, Department of Genomic Medicine, Manchester Academic Health Sciences Centre, Manchester University, Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom
| | - Debra Frost
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
| | - Alex Henderson
- Centre for Life, Institute of Genetic Medicine, Newcastle upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, United Kingdom
| | - Louise Izatt
- Clinical Genetics, Guy's and St. Thomas' NHS Foundation Trust, London, United Kingdom
| | - Kai-Ren Ong
- West Midlands Regional Genetics Service, Birmingham Women's and Children's NHS Foundation Trust, Edgbaston, Birmingham, United Kingdom
| | - Valérie Bonadona
- Université Claude Bernard Lyon 1, Villeurbanne, France; Centre National de la Recherche Scientifique, Unités Mixtes de Recherche, Lyon, France; Centre Léon Bérard, Unité de Prévention et Epidémiologie Génétique, Lyon, France
| | - Isabelle Coupier
- Centre Hospitalier Universitaire de Montpellier, Hôpital Arnaud de Villeneuve, Montpellier, France; Service de Génétique médicale et Oncogénétique, Montpellier, France; Institut National de la Santé et de la Recherche Médicale, Centre de Recherche en Cancérologie de Marseille Val d'Aurel, Montpellier, France
| | - Laurence Faivre
- Genomic and Immunotherapy Medical Institute, Hôpital d'Enfants, Centre Hospitalier Universitaire de Dijon, Dijon, France; Unité d'Oncogénétique, Centre de Lutte Contre le Cancer Georges François Leclerc, Dijon, France
| | | | - Paul Gesta
- Service d'Oncogénétique Régional Poitou-Charentes, Centre Hospitalier Georges Renon, Niort, France
| | - Klaartje van Engelen
- Department of Clinical Genetics, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
| | - Agnes Jager
- Department of Medical Oncology, Family Cancer Clinic, Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands
| | - Fred H Menko
- Family Cancer Clinic, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Marian J E Mourits
- Department of Gynaecology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Christian F Singer
- Department of Obstetrics and Gynecology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
| | - Yen Y Tan
- Department of Obstetrics and Gynecology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
| | - Lenka Foretova
- Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic
| | - Marie Navratilova
- Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic
| | - Rita K Schmutzler
- Medical Faculty, University of Cologne and University Hospital Cologne, Cologne, Germany
| | - Carolina Ellberg
- Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden
| | | | - Trinidad Caldes
- Molecular Oncology Laboratory, Hospital Clinico San Carlos, Instituto de Investigación Hospital Clínico San Carlos, Centro de Investigación Biomédica en Red de Cáncer, Martin Lagos, Madrid, Spain
| | - Jacques Simard
- Genomics Center, Centre Hospitalier Universitaire de Québec - Université Laval Research Center, Québec City, Québec, Canada
| | - Edith Olah
- Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary
| | - Anna Jakubowska
- Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland; Independent Laboratory of Molecular Biology and Genetic Diagnostics, Pomeranian Medical University, Szczecin, Poland
| | - Johanna Rantala
- Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden
| | - Ana Osorio
- Human Genetics Group, Centro Nacional De Investigaciones Oncologicas, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras, Madrid, Spain
| | - John L Hopper
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia
| | - Kelly-Anne Phillips
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia; Department of Oncology, Peter MacCallum Cancer Centre, University of Melbourne, Parkville, Australia; Department of Medical Oncology, Peter MacCallum Cancer Centre, Victoria, Australia
| | - Roger L Milne
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia; Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia
| | - Mary Beth Terry
- Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY
| | - Catherine Noguès
- Département d'Anticipation et de Suivi des Cancers, Oncogénétique Clinique, Institut Paoli-Calmettes, Marseille, France; Institut National de la Santé et de la Recherche Médicale, Institut de Recherche pour le Développement, Sciences Economiques and Sociales de la Santé and Traitement de l'Information Médicale, Aix-Marseille University, Marseille, France
| | - Christoph Engel
- Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Germany
| | - Karin Kast
- Department of Gynecology and Obstetrics, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany
| | - David E Goldgar
- Department of Dermatology, University of Utah School of Medicine, Salt Lake City, UT
| | - Flora E van Leeuwen
- Department of Epidemiology, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Douglas F Easton
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
| | - Nadine Andrieu
- Institut National de la Santé et de la Recherche Médicale, Paris, France; Institut Curie, Paris, France; Mines ParisTech, Fontainebleau, Paris, France; Paris Sciences et Lettres University, Paris, France
| | - Matti A Rookus
- Department of Epidemiology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
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Sim EJ, Ko KP, Ahn C, Park SM, Surh YJ, An S, Kim SW, Lee MH, Lee JW, Lee JE, Kim KS, Yom CK, Kim HA, Park SK. Isoflavone intake on the risk of overall breast cancer and molecular subtypes in women at high risk for hereditary breast cancer. Breast Cancer Res Treat 2020; 184:615-626. [DOI: 10.1007/s10549-020-05875-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Accepted: 08/10/2020] [Indexed: 01/10/2023]
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Breastfeeding and the risk of epithelial ovarian cancer among women with a BRCA1 or BRCA2 mutation. Gynecol Oncol 2020; 159:820-826. [PMID: 33010967 DOI: 10.1016/j.ygyno.2020.09.037] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Accepted: 09/21/2020] [Indexed: 02/02/2023]
Abstract
OBJECTIVE BRCA mutation carriers face a high lifetime risk of developing ovarian cancer. The strong inverse association between breastfeeding and the risk of ovarian cancer is established in the general population but is less well studied among women with a germline BRCA1 or BRCA2 mutation. METHOD Thus, we conducted a matched case-control analysis to evaluate the association between breastfeeding history and the risk of developing ovarian cancer. After matching for year of birth, country of residence, BRCA gene and personal history of breast cancer, a total of 1650 cases and 2702 controls were included in the analysis. Conditional logistic regression was used to estimate the odds ratio (OR) and 95% confidence intervals (CI) associated with various breastfeeding exposures. RESULTS A history of ever-breastfeeding was associated with a 23% reduction in risk (OR = 0.77; 95%CI 0.66-0.90; P = 0.001). The protective effect increased with breastfeeding from one month to seven months after which the association was relatively stable. Compared to women who never breastfed, breastfeeding for seven or more months was associated with a 32% reduction in risk (OR = 0.68; 95%CI 0.57-0.81; P < 0.0001) and did not vary by BRCA gene or age at diagnosis. The combination of breastfeeding and oral contraceptive use was strongly protective (0.47; 95%CI 0.37-0.58; P < 0.0001). CONCLUSIONS These findings support a protective effect of breastfeeding for at least seven months among women with a BRCA1 or BRCA2 mutation, that is independent of oral contraceptive use.
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High frequency of BRCA recurrent mutations in a consecutive series of unselected ovarian cancer patients. REV ROMANA MED LAB 2020. [DOI: 10.2478/rrlm-2020-0026] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Abstract
Hereditary predisposition to breast and ovarian cancer (HBOC) is diagnosed by molecular analysis of deleterious mutations in BRCA genes, allowing oncogenetic follow-up of patients and of their families. BRCA testing addresses only to HBOC families, using restrictive inclusion criteria based on familial history of cancer and age at diagnosis. Sporadic ovarian cancer has high incidence and mortality in Romania, with low median age of diagnosis and possibly a higher magnitude of hereditary contribution comparing to othe populations. However, sporadic ovarian cancers do not qualify for BRCA testing according to inclusion criteria, and a complete BRCA screening of all cancers is neither feasible nor recommended. Despite the large diversity of BRCA mutations worldwide, some recurrent mutations have higher frequencies in diverse populations. Precisely screening for recurrent mutations in a target population allows to rapidly identifying mutation carriers without sequencing the entire BRCA genes. In Romanian population and neighboring countries, several recurrent mutations have already been described. In a consecutive series of 50 sporadic ovarian cancer patients, not qualifying for BRCA complete testing, we screened for 9 most common BRCA mutations, by multiplex-PCR, RFLP and targeted Sanger sequencing. Our results revealed 6 different BRCA mutations in 8 unrelated patients, with a frequency of 16%, much higher than expected. We further recommend screening for the identified mutations in larger series of cancer patients. The results are highly beneficial to cancer patients, healthy relatives, and overall, considering prevention in cancer a priority, to public health system and future of oncogenetics in Romania
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Huber D, Seitz S, Kast K, Emons G, Ortmann O. Use of oral contraceptives in BRCA mutation carriers and risk for ovarian and breast cancer: a systematic review. Arch Gynecol Obstet 2020; 301:875-884. [PMID: 32140806 PMCID: PMC8494665 DOI: 10.1007/s00404-020-05458-w] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2019] [Accepted: 01/27/2020] [Indexed: 11/28/2022]
Abstract
PURPOSE BRCA mutation carriers have an increased risk of developing breast or ovarian cancer. Oral contraception (OC) is known to increase breast cancer and reduce ovarian cancer risk in the general population. This review analyses the published data on OC and risk of cancer in BRCA mutation carriers. METHODS We included all relevant articles published in English from 1995 to 2018. Literature was identified through a search on PubMed and Cochrane Library. RESULTS We included four meta-analyses, one review, one case-control study and one retrospective cohort study on the association between ovarian cancer and OC in BRCA mutation carriers. All report a risk reduction for the OC users and several also describe an inverse correlation with duration of use. Regarding breast cancer, we included four meta-analyses, one review, one case-control study, two case-only studies, one prospective and one retrospective cohort study. Some studies report a risk elevation, while others did not find an association between OC use and breast cancer in BRCA mutation carriers. In other studies, the association was limited to early-onset breast cancer and/or associated with young age at first start of OC. CONCLUSION Oral contraception leads to a risk reduction of ovarian cancer also in BRCA mutation carriers. An increase in breast cancer risk due to OC cannot be excluded. Women with BRCA mutation who consider OC use have to be informed about possible increase in breast cancer risk and alternative contraceptive methods. OC should not be used for the prevention of ovarian cancer in this population.
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Affiliation(s)
- D Huber
- Department of Gynecology and Obstetrics, University Medical Center Regensburg, Regensburg, Germany
| | - S Seitz
- Department of Gynecology and Obstetrics, University Medical Center Regensburg, Regensburg, Germany
| | - K Kast
- Department of Gynecology and Obstetrics, Medical Faculty and University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany
| | - G Emons
- Department of Gynecology and Obstetrics, Georg August University Göttingen, University Medicine, Göttingen, Germany
| | - O Ortmann
- Department of Gynecology and Obstetrics, University Medical Center Regensburg, Regensburg, Germany.
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Non-Surgical Cancer Risk Reduction in BRCA1 Mutation Carriers: Disabling the Remote Control. Cancers (Basel) 2020; 12:cancers12030547. [PMID: 32120796 PMCID: PMC7139938 DOI: 10.3390/cancers12030547] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Revised: 02/21/2020] [Accepted: 02/24/2020] [Indexed: 11/23/2022] Open
Abstract
Women-specific cancers are a major health issue, particularly those associated with the BRCA1 germline mutation carrier state, which include triple-negative basal breast carcinomas and high-grade serous ovarian carcinomas (referred to as extra-uterine Müllerian carcinomas). Whereas many chronic diseases can currently be prevented (e.g., cardiovascular diseases), no recent tangible progress was made in cancer prevention of BRCA1 mutation carriers apart from surgical resections of at-risk organs. This lack of progress is largely due to (1) poor understanding of the initiating events triggered by known risk factors in the development of these cancers, (2) the fact that current preventive measures rely on evidence obtained from adjuvant breast cancer treatment that fail to protect against poor prognostic cancers, and (3) problems with using cancer incidence in high-risk women as an ethically justifiable endpoint in cancer prevention trials. Here, we propose that cancer predisposition in BRCA1 mutation carriers is driven, at least in part, by cell-nonautonomous mechanisms (i.e., driven by consequences of this carrier state on hormonal and other systemic factors controlled in organs other than those that are cancer-prone) and that biomarkers of epigenomic reprogramming, hypothesized to be a direct consequence of such cell-nonautonomous mechanisms, are attractive as intermediate surrogate endpoints to assess the efficacy of cancer risk-reducing strategies targeting these mechanisms.
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Otsuka I, Matsuura T. Screening and Prevention for High-Grade Serous Carcinoma of the Ovary Based on Carcinogenesis-Fallopian Tube- and Ovarian-Derived Tumors and Incessant Retrograde Bleeding. Diagnostics (Basel) 2020; 10:E120. [PMID: 32098383 PMCID: PMC7168061 DOI: 10.3390/diagnostics10020120] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2019] [Revised: 02/18/2020] [Accepted: 02/19/2020] [Indexed: 02/06/2023] Open
Abstract
High-grade serous carcinoma (HGSC) is the most common and lethal subtype of ovarian carcinoma. Many HGSCs are now believed to originate in the fallopian tube epithelium; ovarian surface epithelium is another possible origin. Thus, current screening methods, i.e., ultrasonography and serum CA-125 measurements, have a limitation in their early detection. Recently, circulating biomarkers, such as tumor DNA, autoantibody, and microRNA, have been investigated to detect HGSCs. As cancer cells in the fallopian tube flow into the endometrial cavity, the detection of exfoliated cells, tumor DNA, and proteome from samples obtained from the endometrial cavity or the cervix may be useful. The risk of ovarian serous carcinoma is affected by the use of oral contraceptive and menopausal hormone therapy (MHT). MHT regimens causing endometrial bleeding increase serous carcinoma risk, hence, incessant retrograde bleeding from the endometrial cavity into the Douglas pouch appears to play an important role in high-grade serous carcinogenesis. In this review, we provide an overview of current and novel screening methods and prevention approaches for ovarian and fallopian tube HGSC.
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Affiliation(s)
- Isao Otsuka
- Department of Obstetrics and Gynecology, Kameda Medical Center, Kamogawa 296-8602, Japan;
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19
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Ma YN, Bu HL, Jin CJ, Wang X, Zhang YZ, Zhang H. Peritoneal cancer after bilateral mastectomy, hysterectomy, and bilateral salpingo-oophorectomy with a poor prognosis: A case report and review of the literature. World J Clin Cases 2019; 7:3872-3880. [PMID: 31799317 PMCID: PMC6887594 DOI: 10.12998/wjcc.v7.i22.3872] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2019] [Revised: 09/19/2019] [Accepted: 10/05/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Primary peritoneal cancer (PPC) patients with BRCA mutations have a good prognosis; however, for patients with BRCA mutations who are diagnosed with PPC after prophylactic salpingo-oophorectomy (PSO), the prognosis is poor, and survival information is scarce.
CASE SUMMARY We treated a 56-year-old woman with PPC after bilateral mastectomy, hysterectomy, and bilateral salpingo-oophorectomy. This patient had primary drug resistance and died 12 mo after the diagnosis of PPC. The genetic test performed on this patient indicated the presence of a germline BRCA1 mutation. We searched the PubMed, Scopus, and Cochrane databases and extracted studies of patients with BRCA mutations who developed PPC after PSO. After a detailed literature search, we found 30 cases, 7 of which had a history of breast cancer, 14 of which had no history of breast cancer, and 9 of which had an unknown history. The average age of PSO patients was 48.86 years old (range, 31-64 years). The average time interval between the diagnosis of PPC and preventive surgery was 61.03 mo (range, 12-292 mo). The 2-year survival rate for this patient population was 78.26% (18/23), the 3-year survival rate was 50.00% (9/18), and the 5-year survival rate was 6.25% (1/16).
CONCLUSION Patients with BRCA mutations who are diagnosed with PPC after preventative surgery have a poor prognosis. Prevention measures and treatments for these patients need more attention.
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Affiliation(s)
- Ya-Na Ma
- Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan 250012, Shandong Province, China
| | - Hua-Lei Bu
- Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan 250012, Shandong Province, China
| | - Cheng-Juan Jin
- Department of Obstetrics and Gynecology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 201620, China
| | - Xia Wang
- Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan 250012, Shandong Province, China
| | - You-Zhong Zhang
- Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan 250012, Shandong Province, China
| | - Hui Zhang
- Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan 250012, Shandong Province, China
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20
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Kyo S, Ishikawa N, Nakamura K, Nakayama K. The fallopian tube as origin of ovarian cancer: Change of diagnostic and preventive strategies. Cancer Med 2019; 9:421-431. [PMID: 31769234 PMCID: PMC6970023 DOI: 10.1002/cam4.2725] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2019] [Revised: 11/06/2019] [Accepted: 11/08/2019] [Indexed: 01/20/2023] Open
Abstract
Ovarian cancer is the leading cause of gynecologic cancer death in the world, and its prevention and early diagnosis remain the key to its treatment, especially for high‐grade serous carcinoma (HGSC). Accumulating epidemiological and molecular evidence has shown that HGSC originates from fallopian tube secretory cells through serous tubal intraepithelial carcinoma. Comprehensive molecular analyses and mouse studies have uncovered the key driver events for serous carcinogenesis, providing novel molecular targets. Risk‐reducing bilateral salpingo‐oophorectomy (RRSO) has been proposed to reduce the subsequent occurrence of serous carcinoma in high‐risk patients with BRCA mutations. However, there is no management strategy for isolated precursors detected at RRSO, and the role of subsequent surgery or chemotherapy in preventing serous carcinoma remains unclear. Surgical menopause due to RRSO provides a variety of problems related to patients’ quality of life, and the risks and benefits of hormone replacement are under investigation, especially for women without a previous history of breast cancer. An additional surgical option, salpingectomy with delayed oophorectomy, has been proposed to prevent surgical menopause. The number of opportunistic salpingectomies at the time of surgery for benign disease to prevent the future occurrence of HGSC has increased worldwide. Thus, the changing concept of the origin of serous carcinoma has provided us a great opportunity to develop novel diagnostic and therapeutic approaches.
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Affiliation(s)
- Satoru Kyo
- Department of Obstetrics and Gynecology, Shimane University Faculty of Medicine, Izumo, Shimane, Japan
| | - Noriyoshi Ishikawa
- Department of Pathology, Shimane University Faculty of Medicine, Izumo, Shimane, Japan
| | - Kohei Nakamura
- Department of Obstetrics and Gynecology, Shimane University Faculty of Medicine, Izumo, Shimane, Japan
| | - Kentaro Nakayama
- Department of Obstetrics and Gynecology, Shimane University Faculty of Medicine, Izumo, Shimane, Japan
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21
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Madariaga A, Lheureux S, Oza AM. Tailoring Ovarian Cancer Treatment: Implications of BRCA1/2 Mutations. Cancers (Basel) 2019; 11:E416. [PMID: 30909618 PMCID: PMC6468364 DOI: 10.3390/cancers11030416] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2019] [Revised: 03/13/2019] [Accepted: 03/18/2019] [Indexed: 02/07/2023] Open
Abstract
High grade serous ovarian cancer (HGSOC) is the most common epithelial ovarian cancer, harbouring more than 20% germline or somatic mutations in the tumour suppressor genes BRCA1 and BRCA2. These genes are involved in both DNA damage repair process via homologous recombination (HR) and transcriptional regulation. BRCA mutation confers distinct characteristics, including an increased response to DNA-damaging agents, such us platinum chemotherapy and poly-ADP ribose polymerase inhibitors (PARPi). However, several mechanisms of resistance to these agents have been described, including increased HR capacity through reverse BRCA mutations, non-homologous end-joint (NHEJ) repair alterations and drug efflux pumps. Current treatments of ovarian cancer including surgery, chemotherapy, targeted treatment and maintenance strategies, as well as resistance mechanisms will be reviewed, focusing on future trends with respect to BRCA mutation carriers.
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Affiliation(s)
- Ainhoa Madariaga
- Division of Medical Oncology & Hematology, Princess Margaret Cancer Center, Toronto, ON M5G 2M9, Canada.
| | - Stephanie Lheureux
- Division of Medical Oncology & Hematology, Princess Margaret Cancer Center, Toronto, ON M5G 2M9, Canada.
| | - Amit M Oza
- Division of Medical Oncology & Hematology, Princess Margaret Cancer Center, Toronto, ON M5G 2M9, Canada.
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Abstract
High grade serous ovarian cancer (HGSOC) is the most common epithelial ovarian cancer, harbouring more than 20% germline or somatic mutations in the tumour suppressor genes BRCA1 and BRCA2. These genes are involved in both DNA damage repair process via homologous recombination (HR) and transcriptional regulation. BRCA mutation confers distinct characteristics, including an increased response to DNA-damaging agents, such us platinum chemotherapy and poly-ADP ribose polymerase inhibitors (PARPi). However, several mechanisms of resistance to these agents have been described, including increased HR capacity through reverse BRCA mutations, non-homologous end-joint (NHEJ) repair alterations and drug efflux pumps. Current treatments of ovarian cancer including surgery, chemotherapy, targeted treatment and maintenance strategies, as well as resistance mechanisms will be reviewed, focusing on future trends with respect to BRCA mutation carriers.
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23
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Madariaga A, Lheureux S, Oza AM. Tailoring Ovarian Cancer Treatment: Implications of BRCA1/2 Mutations. Cancers (Basel) 2019. [PMID: 30909618 DOI: 10.3390/cancers11030416]+[] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
High grade serous ovarian cancer (HGSOC) is the most common epithelial ovarian cancer, harbouring more than 20% germline or somatic mutations in the tumour suppressor genes BRCA1 and BRCA2. These genes are involved in both DNA damage repair process via homologous recombination (HR) and transcriptional regulation. BRCA mutation confers distinct characteristics, including an increased response to DNA-damaging agents, such us platinum chemotherapy and poly-ADP ribose polymerase inhibitors (PARPi). However, several mechanisms of resistance to these agents have been described, including increased HR capacity through reverse BRCA mutations, non-homologous end-joint (NHEJ) repair alterations and drug efflux pumps. Current treatments of ovarian cancer including surgery, chemotherapy, targeted treatment and maintenance strategies, as well as resistance mechanisms will be reviewed, focusing on future trends with respect to BRCA mutation carriers.
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Affiliation(s)
- Ainhoa Madariaga
- Division of Medical Oncology & Hematology, Princess Margaret Cancer Center, Toronto, ON M5G 2M9, Canada.
| | - Stephanie Lheureux
- Division of Medical Oncology & Hematology, Princess Margaret Cancer Center, Toronto, ON M5G 2M9, Canada.
| | - Amit M Oza
- Division of Medical Oncology & Hematology, Princess Margaret Cancer Center, Toronto, ON M5G 2M9, Canada.
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24
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Williams WV, Mitchell LA, Carlson SK, Raviele KM. Association of Combined Estrogen-Progestogen and Progestogen-Only Contraceptives with the Development of Cancer. LINACRE QUARTERLY 2019; 85:412-452. [PMID: 32431377 DOI: 10.1177/0024363918811637] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Combined estrogen-progestogen contraceptives (oral contraceptives or OCs) and progestogen-only contraceptives (POCs) are synthetic steroids that bind to steroid hormone receptors, which are widespread throughout the body. They have a profound effect on cellular physiology. Combined OCs have been classified by the International Agency for Research on Cancer (IARC) as Group 1 carcinogens, but their findings have not been updated recently. In order to update the information and better understand the impact that OCs and POCs have on the risk of development of cancers, a comprehensive literature search was undertaken, focusing on more recently published papers. In agreement with the IARC, the recent literature confirms an increased risk of breast cancer and cervical cancer with the use of OCs. The recent literature also confirms the IARC conclusion that OCs decrease the risk of ovarian and endometrial cancers. However, there is little support from recent studies for the IARC conclusion that OCs decrease the risk of colorectal cancer or increase the risk of liver cancer. For liver cancer, this may be due to the recent studies having been performed in areas where hepatitis is endemic. In one large observational study, POCs also appear to increase the overall risk of developing cancer. OCs and POCs appear to increase the overall risk of cancer when carefully performed studies with the least intrinsic bias are considered. Summary OCs have been classified as cancer-causing agents, especially leading to increases in breast cancer and cervical cancer. A review of the recent scientific literature was performed to see whether this still appears to be the case. The recent literature supports the cancer-causing role of OCs especially for breast cancer and cervical cancer. Studies also indicate that progesterone-only contraceptives (such as implants and vaginal rings) also can cause cancer. This is especially true for breast cancer and cervical cancer.
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Affiliation(s)
- William V Williams
- BriaCell Therapeutics Corporation, West Vancouver, British Columbia, Canada.,University of Pennsylvania, Philadelphia, PA, USA
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25
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Gockley AA, Elias KM. Fallopian tube tumorigenesis and clinical implications for ovarian cancer risk-reduction. Cancer Treat Rev 2018; 69:66-71. [DOI: 10.1016/j.ctrv.2018.06.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2018] [Revised: 06/04/2018] [Accepted: 06/09/2018] [Indexed: 12/20/2022]
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Prophylactic bilateral salpingectomy for the prevention of ovarian cancers: What is happening in Italy? Eur J Cancer Prev 2018; 25:410-5. [PMID: 26275007 DOI: 10.1097/cej.0000000000000191] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
In 2011, the Society of Gynecologic Oncology of Canada encouraged physicians to discuss with their patients the risks and benefits of prophylactic bilateral salpingectomy (PBS) at the time of hysterectomy or tubal ligation for prevention of ovarian cancers (OCs). The aim of this study was to examine obstetrician-gynaecologists' knowledge, opinions and practice patterns relating to opportunistic salpingectomy in the general population. An anonymous electronic survey was sent to residents, academic and hospital staff in Italian OBGYN departments. The survey included questions on demographics, knowledge and attitudes in terms of the implementation of PBS in women at average population risk of OC. At least 80% of the 479 respondents reported performing PBS during hysterectomy for benign indications, chiefly with the intent of OC risk reduction but also to decrease the risk of reoperation and subsequent tubal pathologies. Among the 86 colleagues who do not routinely perform PBS, more than 50% stated that they have doubts regarding the benefits associated with the procedure. Most of the respondents declared that they were familiar with the literature on the topic and were aware of the data reporting the safety of the procedure, and only 21 (4.53%) had never heard of PBS. Over 40% of the respondents worked in hospitals in southern Italy. PBS as a prophylactic measure to reduce the incidence of OC is a well-known strategy among the Italian OBGYNs interviewed. Given the unequal distribution of respondents, however, wider educational initiatives should be undertaken, at least in Italy, to increase the implementation of salpingectomy among OBGYNs.
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27
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Chene G, Lamblin G. [Exclusive salpingectomy or prophylactic salpingo-oophorectomy? Critical analysis of the latest French guidelines]. ACTA ACUST UNITED AC 2017; 46:1-3. [PMID: 29203396 DOI: 10.1016/j.gofs.2017.10.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2017] [Indexed: 11/26/2022]
Affiliation(s)
- G Chene
- Département de gynécologie, hôpital Femme-Mère-Enfant, HFME, hospices civils de Lyon, 59, boulevard Pinel, 69000 Lyon, France; Université Claude-Bernard Lyon 1, EMR 3738, 69000 Lyon, France.
| | - G Lamblin
- Département de gynécologie, hôpital Femme-Mère-Enfant, HFME, hospices civils de Lyon, 59, boulevard Pinel, 69000 Lyon, France
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28
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Abstract
Ovarian carcinoma is the most lethal malignancy of the female genital tract. Population-based trials in the general population have not demonstrated that screening improves early detection or survival. Therefore, application of prevention strategies is vital to improving outcomes from this disease. Surgical prevention reduces risk and prophylactic risk-reducing salpingo-oophorectomy is the most effective means to prevent ovarian carcinoma in the high-risk patient although the risks do not outweigh the benefits in average risk patients. Other surgical and medical options have unknown or limited efficacy in the high-risk patient. In this review, we define the patient at high risk for ovarian cancer, discuss how to identify these women and weigh their available ovarian cancer prevention strategies.
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Affiliation(s)
- Sarah M. Temkin
- Virginia Commonwealth University, Department of Obstetrics and Gynecology, Richmond, VA, USA
| | - Jennifer Bergstrom
- Johns Hopkins School of Medicine, Kelly Gynecologic Oncology Service, Baltimore, MD, USA
| | - Goli Samimi
- Division of Cancer Prevention, National Cancer Institute, Bethesda, MD, USA
| | - Lori Minasian
- Division of Cancer Prevention, National Cancer Institute, Bethesda, MD, USA
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29
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De Felice F, Marchetti C, Boccia SM, Romito A, Sassu CM, Porpora MG, Muzii L, Tombolini V, Benedetti Panici P. Risk-reducing salpingo-oophorectomy in BRCA1 and BRCA2 mutated patients: An evidence-based approach on what women should know. Cancer Treat Rev 2017; 61:1-5. [PMID: 29028552 DOI: 10.1016/j.ctrv.2017.09.005] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2017] [Revised: 09/18/2017] [Accepted: 09/20/2017] [Indexed: 12/12/2022]
Abstract
This review is focused on the ovarian cancer risk reduction management in BRCA mutation carriers and is intended to assist with clinical decision-making. Obviously, treatment decisions must be based on the available evidence. Despite risk-reducing salpingo-oophorectomy is firmly recommended, several separate questions can be raised to address the variety of intense controversy of this approach. A special emphasis lies in the effective preventive surgical measure against ovarian cancer risk, in an attempt to detect the optimal timing and mitigate the impact on patients. The long term implications of risk-reducing salpingo-oophorectomy as well as hormone replacement therapy are also actively debated. This is expected to represent an opportunity for improved management modelling of BRCA mutated patients.
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Affiliation(s)
- F De Felice
- Department of Radiotherapy, Policlinico Umberto I, "Sapienza" University of Rome, Rome, Italy.
| | - C Marchetti
- Department of Gynecological and Obstetrical Sciences and Urological Sciences, "Sapienza" University of Rome, Rome, Italy.
| | - S M Boccia
- Department of Gynecological and Obstetrical Sciences and Urological Sciences, "Sapienza" University of Rome, Rome, Italy.
| | - A Romito
- Department of Gynecological and Obstetrical Sciences and Urological Sciences, "Sapienza" University of Rome, Rome, Italy.
| | - C M Sassu
- Department of Gynecological and Obstetrical Sciences and Urological Sciences, "Sapienza" University of Rome, Rome, Italy.
| | - M G Porpora
- Department of Gynecological and Obstetrical Sciences and Urological Sciences, "Sapienza" University of Rome, Rome, Italy.
| | - L Muzii
- Department of Gynecological and Obstetrical Sciences and Urological Sciences, "Sapienza" University of Rome, Rome, Italy.
| | - V Tombolini
- Department of Radiotherapy, Policlinico Umberto I, "Sapienza" University of Rome, Rome, Italy.
| | - P Benedetti Panici
- Department of Gynecological and Obstetrical Sciences and Urological Sciences, "Sapienza" University of Rome, Rome, Italy.
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30
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Paterson R, Phillips KA. Genetic testing in women with breast cancer: implications for treatment. Expert Rev Anticancer Ther 2017; 17:991-1002. [PMID: 28853307 DOI: 10.1080/14737140.2017.1374175] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
INTRODUCTION Mutations in either the BRCA1 or BRCA2 genes are responsible for approximately 42,000 cases of breast cancer annually. Identifying these germline mutations in a woman with breast cancer is important because it can influence her immediate and long-term management and has important implications for other family members. Areas covered: This review highlights how treatment-focussed genetic testing for BRCA1 and BRCA2 mutations can potentially influence cancer treatment and secondary prevention decisions in women with breast cancer. Expert commentary: Testing women with breast cancer for BRCA1 and BRCA2 germline mutations has the potential to decrease cancer burden and improve cancer outcomes. It can help optimise surgical and systemic therapy approaches. Clinicians should actively consider whether genetic testing is appropriate for each woman with breast cancer, and if so should instigate it early in the treatment trajectory when it can most influence cancer care.
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Affiliation(s)
- Robin Paterson
- a Australia and New Zealand Breast Cancer Trials Group , Newcastle , Australia.,b School of Medicine and Public Health , University of Newcastle , Newcastle , Australia
| | - Kelly-Anne Phillips
- a Australia and New Zealand Breast Cancer Trials Group , Newcastle , Australia.,c Division of Cancer Medicine , Peter MacCallum Cancer Centre , Melbourne , Australia.,d Sir Peter MacCallum Department of Oncology , University of Melbourne , Parkville , Australia.,e School of Population and Global Health , University of Melbourne , Carlton , Australia
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31
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Family Communication, Risk Perception and Cancer Knowledge of Young Adults from BRCA1/2 Families: a Systematic Review. J Genet Couns 2017; 26:1179-1196. [DOI: 10.1007/s10897-017-0125-4] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2016] [Accepted: 06/05/2017] [Indexed: 12/19/2022]
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32
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Karnezis AN, Cho KR, Gilks CB, Pearce CL, Huntsman DG. The disparate origins of ovarian cancers: pathogenesis and prevention strategies. Nat Rev Cancer 2017; 17:65-74. [PMID: 27885265 DOI: 10.1038/nrc.2016.113] [Citation(s) in RCA: 219] [Impact Index Per Article: 27.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Ovarian cancer is the fifth cause of cancer-related death in women and comprises a histologically and genetically broad range of tumours, including those of epithelial, sex cord-stromal and germ cell origin. Recent evidence indicates that high-grade serous ovarian carcinoma, clear cell carcinoma and endometrioid carcinoma primarily arise from tissues that are not normally present in the ovary. These histogenetic pathways are informing risk-reduction strategies for the prevention of ovarian and ovary-associated cancers and have highlighted the importance of the seemingly unique ovarian microenvironment.
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Affiliation(s)
- Anthony N Karnezis
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V5Z 1M9, Canada
| | - Kathleen R Cho
- Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
| | - C Blake Gilks
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V5Z 1M9, Canada
| | - Celeste Leigh Pearce
- Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan 48109, USA
| | - David G Huntsman
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V5Z 1M9, Canada
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Suh DH, Kim M, Kim HJ, Lee KH, Kim JW. Major clinical research advances in gynecologic cancer in 2015. J Gynecol Oncol 2016; 27:e53. [PMID: 27775259 PMCID: PMC5078817 DOI: 10.3802/jgo.2016.27.e53] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2016] [Accepted: 10/17/2016] [Indexed: 02/07/2023] Open
Abstract
In 2015, fourteen topics were selected as major research advances in gynecologic oncology. For ovarian cancer, high-level evidence for annual screening with multimodal strategy which could reduce ovarian cancer deaths was reported. The best preventive strategies with current status of evidence level were also summarized. Final report of chemotherapy or upfront surgery (CHORUS) trial of neoadjuvant chemotherapy in advanced stage ovarian cancer and individualized therapy based on gene characteristics followed. There was no sign of abating in great interest in immunotherapy as well as targeted therapies in various gynecologic cancers. The fifth Ovarian Cancer Consensus Conference which was held in November 7-9 in Tokyo was briefly introduced. For cervical cancer, update of human papillomavirus vaccines regarding two-dose regimen, 9-valent vaccine, and therapeutic vaccine was reviewed. For corpus cancer, the safety concern of power morcellation in presumed fibroids was explored again with regard to age and prevalence of corpus malignancy. Hormone therapy and endometrial cancer risk, trabectedin as an option for leiomyosarcoma, endometrial cancer and Lynch syndrome, and the radiation therapy guidelines were also discussed. In addition, adjuvant therapy in vulvar cancer and the updated of targeted therapy in gynecologic cancer were addressed. For breast cancer, palbociclib in hormone-receptor-positive advanced disease, oncotype DX Recurrence Score in low-risk patients, regional nodal irradiation to internal mammary, supraclavicular, and axillary lymph nodes, and cavity shave margins were summarized as the last topics covered in this review.
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Affiliation(s)
- Dong Hoon Suh
- Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Miseon Kim
- Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Hak Jae Kim
- Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea
| | - Kyung Hun Lee
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
| | - Jae Weon Kim
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea.
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34
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Webb PM, Jordan SJ. Epidemiology of epithelial ovarian cancer. Best Pract Res Clin Obstet Gynaecol 2016; 41:3-14. [PMID: 27743768 DOI: 10.1016/j.bpobgyn.2016.08.006] [Citation(s) in RCA: 628] [Impact Index Per Article: 69.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2016] [Accepted: 08/17/2016] [Indexed: 02/08/2023]
Abstract
Globally, ovarian cancer is the seventh most common cancer in women and the eighth most common cause of cancer death, with five-year survival rates below 45%. Although age-standardised rates are stable or falling in most high-income countries, they are rising in many low and middle income countries. Furthermore, with increasing life-expectancy, the number of cases diagnosed each year is increasing. To control ovarian cancer we need to understand the causes. This will allow better prediction of those at greatest risk for whom screening might be appropriate, while identification of potentially modifable causes provides an opportunity for intervention to reduce rates. In this paper we will summarise the current state of knowledge regarding the known and possible causes of epithelial ovarian cancer and discuss some of the main theories of ovarian carcinogenesis. We will also briefly review the relationship between lifestyle and survival after a diagnosis of ovarian cancer.
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Affiliation(s)
- Penelope M Webb
- QIMR Berghofer Medical Research Institute, Locked Bag 2000 Royal Brisbane Hospital, Brisbane, Queensland 4029, Australia; School of Public Health, The University of Queensland, Public Health Building, Corner of Herston Road & Wyndham Street, Herston, Queensland 4006, Australia.
| | - Susan J Jordan
- QIMR Berghofer Medical Research Institute, Locked Bag 2000 Royal Brisbane Hospital, Brisbane, Queensland 4029, Australia; School of Public Health, The University of Queensland, Public Health Building, Corner of Herston Road & Wyndham Street, Herston, Queensland 4006, Australia.
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35
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Milne RL, Antoniou AC. Modifiers of breast and ovarian cancer risks for BRCA1 and BRCA2 mutation carriers. Endocr Relat Cancer 2016; 23:T69-84. [PMID: 27528622 DOI: 10.1530/erc-16-0277] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2016] [Accepted: 08/15/2016] [Indexed: 12/20/2022]
Abstract
Pathogenic mutations in BRCA1 and BRCA2 are associated with high risks of breast and ovarian cancer. However, penetrance estimates for mutation carriers have been found to vary substantially between studies, and the observed differences in risk are consistent with the hypothesis that genetic and environmental factors modify cancer risks for women with these mutations. Direct evidence that this is the case has emerged in the past decade, through large-scale international collaborative efforts. Here, we describe the methodological challenges in the identification and characterisation of these risk-modifying factors, review the latest evidence on genetic and lifestyle/hormonal risk factors that modify breast and ovarian cancer risks for women with BRCA1 and BRCA2 mutations and outline the implications of these findings for cancer risk prediction. We also review the unresolved issues in this area of research and identify strategies of clinical implementation so that women with BRCA1 and BRCA2 mutations are no longer counselled on the basis of 'average' risk estimates.
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Affiliation(s)
- Roger L Milne
- Cancer Epidemiology CentreCancer Council Victoria, Melbourne, Australia Centre for Epidemiology and BiostatisticsMelbourne School of Population and Global Health, University of Melbourne, Parkville, Victoria, Australia
| | - Antonis C Antoniou
- Centre for Cancer Genetic EpidemiologyDepartment of Public Health and Primary Care, University of Cambridge, Cambridge, UK
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Weiderpass E, Tyczynski JE. Epidemiology of Patients with Ovarian Cancer with and Without a BRCA1/2 Mutation. Mol Diagn Ther 2016; 19:351-64. [PMID: 26476542 DOI: 10.1007/s40291-015-0168-x] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
Ovarian cancer survival rates have improved only slightly in recent decades; however, treatment of this disease is expected to undergo rapid change as strategies incorporating molecular-targeted therapies enter clinical practice. Carriers of deleterious mutations (defined as a harmful mutation) in either the BRCA1 or BRCA2 gene (BRCAm) have a significantly increased risk of developing ovarian cancer. Epidemiology data in large (>500 patients) unselected ovarian cancer populations suggest that the expected incidence rate for BRCAm in this population is 12-14 %. Patients with a BRCAm are typically diagnosed at a younger age than those without a BRCAm. Associations with BRCAm vary according to ethnicity, with women of Ashkenazi Jewish descent being 10 times more likely to have a BRCAm than the general population. In terms of survival, patients with invasive epithelial ovarian cancer who have a BRCAm may have improved overall survival compared with patients who do not carry a BRCAm. Although genetic testing for BRCAm remains relatively uncommon in ovarian cancer patients, testing is becoming cheaper and increasingly accessible; however, this approach is not without numerous social, ethical and policy issues. Current guidelines recommend BRCAm testing in specific ovarian cancer patients only; however, with the emergence of treatments that are targeted at patients with a BRCAm, genetic testing of all patients with high-grade serous ovarian cancer may lead to improved patient outcomes in this patient population. Knowledge of BRCAm status could, therefore, help to inform treatment decisions and identify relatives at increased risk of developing cancer.
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Affiliation(s)
- Elisabete Weiderpass
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, PO Box 281, 171 77, Stockholm, Sweden. .,Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway. .,Department of Research, Cancer Registry of Norway, Oslo, Norway. .,Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland.
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Jordan SJ, Wilson LF, Nagle CM, Green AC, Olsen CM, Bain CJ, Pandeya N, Whiteman DC, Webb PM. Cancers in Australia in 2010 attributable to total breastfeeding durations of 12 months or less by parous women. Aust N Z J Public Health 2016; 39:418-21. [PMID: 26437725 PMCID: PMC4606743 DOI: 10.1111/1753-6405.12457] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2015] [Revised: 05/01/2015] [Accepted: 06/01/2015] [Indexed: 01/23/2023] Open
Abstract
Objectives To estimate the proportion and number of cancers occurring in Australia in 2010 attributable to parous women having breastfed for total durations of ≤12 months. Methods We estimated the population attributable fraction (PAF) of breast cancers (the only cancer site with convincing evidence of causal association) associated with women breastfeeding for ≤12 months in total, using standard formulae incorporating breastfeeding prevalence data, relative risks associated with breastfeeding and cancer incidence. We also estimated the proportion change in disease incidence (potential impact fraction [PIF]) that might have occurred under two hypothetical scenarios of women breastfeeding for longer durations. Results An estimated 235 (1.7%) breast cancer cases that occurred in Australian in 2010 could be attributed to women breastfeeding for total durations of ≤12 months. Assuming a hypothetical increase in breastfeeding, we estimated that the number of breast cancers prevented would range from 36 to 51 (prevented fraction = 0.3% to 0.4%). Conclusions More than 200 breast cancers were attributable to women breastfeeding for total durations of ≤12 months. Implications Policies to increase breastfeeding duration may help prevent breast cancers in the future.
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Affiliation(s)
- Susan J Jordan
- QIMR Berghofer Medical Research Institute, Queensland.,School of Public Health, The University of Queensland
| | | | - Christina M Nagle
- QIMR Berghofer Medical Research Institute, Queensland.,School of Public Health, The University of Queensland
| | - Adele C Green
- QIMR Berghofer Medical Research Institute, Queensland.,School of Public Health, The University of Queensland.,Cancer Research UK, Manchester Institute and Institute of Inflammation and Repair, University of Manchester, United Kingdom
| | - Catherine M Olsen
- QIMR Berghofer Medical Research Institute, Queensland.,School of Public Health, The University of Queensland
| | - Christopher J Bain
- QIMR Berghofer Medical Research Institute, Queensland.,National Centre for Epidemiology and Population Health, Research School of Population Health, Australian National University, Australian Capital Territory
| | - Nirmala Pandeya
- QIMR Berghofer Medical Research Institute, Queensland.,School of Public Health, The University of Queensland
| | - David C Whiteman
- QIMR Berghofer Medical Research Institute, Queensland.,School of Public Health, The University of Queensland
| | - Penelope M Webb
- QIMR Berghofer Medical Research Institute, Queensland.,School of Public Health, The University of Queensland
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Weitzel JN. The Genetics of Breast Cancer: What the Surgical Oncologist Needs to Know. Surg Oncol Clin N Am 2016; 24:705-32. [PMID: 26363538 DOI: 10.1016/j.soc.2015.06.011] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
This article summarizes the impact of germline predisposition to breast cancer on the surgical management of breast cancer and breast cancer risk. Surgical implications of germline predisposition to breast cancer are now more nuanced due to the application of increasingly more complicated next-generation sequencing-based tests. The rapid pace of change will continue to challenge paradigms for genetic cancer risk assessment, which can influence the medical and surgical management of breast cancer risk as well as strategies for screening and for risk reduction.
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Affiliation(s)
- Jeffrey N Weitzel
- Division of Clinical Cancer Genetics, City of Hope Comprehensive Cancer Center, 1500 East Duarte Road, Duarte, CA 91010, USA.
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James PA, Sawyer S, Boyle S, Young MA, Kovalenko S, Doherty R, McKinley J, Alsop K, Beshay V, Harris M, Fox S, Lindeman GJ, Mitchell G. Large genomic rearrangements in the familial breast and ovarian cancer gene BRCA1 are associated with an increased frequency of high risk features. Fam Cancer 2016; 14:287-95. [PMID: 25678442 DOI: 10.1007/s10689-015-9785-0] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Large genomic rearrangements (LGRs) account for at least 10% of the mutations in BRCA1 and 5% of BRCA2 mutations in outbred hereditary breast and ovarian cancer (HBOC) families. Data from some series suggest LGRs represent particularly penetrant mutations. 1,034 index cases from HBOC families underwent comprehensive BRCA1 and BRCA2 mutation testing, including screening for LGRs. The personal and family history of 254 identified mutation carriers were compared based on mutation type. Thirty-six LGRs were detected; 32/122 (26%) BRCA1 and 4/132 (3%) BRCA2 mutations. High risk features (bilateral breast cancer, diagnosis <40 years, ovarian cancer, male breast cancer) were more commonly associated with an LGR than a non-LGR mutation (p = 0.008), In families with a BRCA1 LGR the mean age of breast cancer diagnosis was younger than in families with a non-LGR BRCA1 mutation (42.5 vs. 46.1 years, p = 0.007). Across the entire group of mutation positive families the number of relatives affected by breast or ovarian cancer was increased [LGR 3.7 vs. non- LGR 2.8 per family, p value (adjusted for genotype) = 0.047]. Excluding index cases, the odds ratio for breast cancer in BRCA1 families with an LGR was 1.42 (95% CI 1.24-1.63) and for ovarian cancer 1.66 (95% CI 1.10-2.49). The increased cancer risk was reflected in significantly higher risk assessments by mutation prediction tools. LGRs are associated with higher cancer risks. If validated, LGRs could be included in cancer risk prediction tools to improve personalised cancer risk prediction estimates and may guide cost-minimising mutation screening strategies in some healthcare settings.
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Affiliation(s)
- Paul A James
- Familial Cancer Centre, Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne, VIC, 3002, Australia
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Prophylactic salpingectomy and prophylactic salpingoophorectomy for adnexal high-grade serous epithelial carcinoma: A reappraisal. Surg Oncol 2015; 24:335-44. [DOI: 10.1016/j.suronc.2015.09.008] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2015] [Revised: 09/27/2015] [Accepted: 09/30/2015] [Indexed: 01/22/2023]
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Chowdhury R, Sinha B, Sankar MJ, Taneja S, Bhandari N, Rollins N, Bahl R, Martines J. Breastfeeding and maternal health outcomes: a systematic review and meta-analysis. Acta Paediatr 2015; 104:96-113. [PMID: 26172878 PMCID: PMC4670483 DOI: 10.1111/apa.13102] [Citation(s) in RCA: 630] [Impact Index Per Article: 63.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2015] [Revised: 06/16/2015] [Accepted: 06/18/2015] [Indexed: 12/12/2022]
Abstract
AIM To evaluate the effect of breastfeeding on long-term (breast carcinoma, ovarian carcinoma, osteoporosis and type 2 diabetes mellitus) and short-term (lactational amenorrhoea, postpartum depression, postpartum weight change) maternal health outcomes. METHODS A systematic literature search was conducted in PubMed, Cochrane Library and CABI databases. Outcome estimates of odds ratios or relative risks or standardised mean differences were pooled. In cases of heterogeneity, subgroup analysis and meta-regression were explored. RESULTS Breastfeeding >12 months was associated with reduced risk of breast and ovarian carcinoma by 26% and 37%, respectively. No conclusive evidence of an association between breastfeeding and bone mineral density was found. Breastfeeding was associated with 32% lower risk of type 2 diabetes. Exclusive breastfeeding and predominant breastfeeding were associated with longer duration of amenorrhoea. Shorter duration of breastfeeding was associated with higher risk of postpartum depression. Evidence suggesting an association of breastfeeding with postpartum weight change was lacking. CONCLUSION This review supports the hypothesis that breastfeeding is protective against breast and ovarian carcinoma, and exclusive breastfeeding and predominant breastfeeding increase the duration of lactational amenorrhoea. There is evidence that breastfeeding reduces the risk of type 2 diabetes. However, an association between breastfeeding and bone mineral density or maternal depression or postpartum weight change was not evident.
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Affiliation(s)
- Ranadip Chowdhury
- Centre for Health Research and Development, Society for Applied StudiesNew Delhi, India
| | - Bireshwar Sinha
- Centre for Health Research and Development, Society for Applied StudiesNew Delhi, India
| | - Mari Jeeva Sankar
- Newborn Health Knowledge Centre, ICMR Centre for Advanced Research in Newborn Health, Department of Paediatrics, All India Institute of Medical SciencesNew Delhi, India
| | - Sunita Taneja
- Centre for Health Research and Development, Society for Applied StudiesNew Delhi, India
| | - Nita Bhandari
- Centre for Health Research and Development, Society for Applied StudiesNew Delhi, India
| | - Nigel Rollins
- Department of Maternal, Newborn, Child and Adolescent Health, World Health OrganizationGeneva, Switzerland
| | - Rajiv Bahl
- Department of Maternal, Newborn, Child and Adolescent Health, World Health OrganizationGeneva, Switzerland
| | - Jose Martines
- Centre for Intervention Science in Maternal and Child Health, Centre for International Health, University of BergenBergen, Norway
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Abstract
As the testing criteria for BRCA expand, we are identifying a greater number of young women at significant risk for breast and ovarian cancer. Fortunately, there is strong evidence to support risk reduction from mastectomy and oophorectomy. However, these surgeries come with significant psychological and physical health consequences. For breast cancer, screening with mammogram and magnetic resonance imaging may be a reasonable approach for a woman who does not desire surgery. However, there is no evidence to suggest any efficacy in screening for ovarian cancer, and women electing to not undergo surgery must have a detailed discussion with their physician regarding the risks and benefits of different management strategies. As more women are electing to undergo surgical risk reduction, providers must also be able to counsel and care for these women who will face unique health challenges after surgical menopause at a young age. A review of the current evidence behind management of the BRCA woman follows, with a focus on areas of controversy and current research.
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Abstract
PURPOSE OF REVIEW As more women with an inherited increased risk of gynecologic cancer are identified, the clinician will be challenged to counsel these women on risk-reducing strategies. RECENT FINDINGS Although there are some recent studies that show potential for ovarian cancer surveillance strategies, there remains no definitive evidence that surveillance leads to a stage shift or a reduction in mortality. Recent studies support the following conclusions: first, oral contraceptive use reduces ovarian cancer risk without significantly increasing breast cancer risk, second, salpingo-oophorectomy leads to a reduction in ovarian cancer, breast cancer, and overall mortality for women who are carriers of BRCA1 and BRCA2 mutations, and third, the 'ovarian cancers' associated with BRCA mutations actually include fallopian tube and peritoneal cancer and may have a precursor lesion in the fallopian tube; this observation has prompted the provocative suggestion of removing the fallopian tube to reduce ovarian cancer risk. SUMMARY Because of the interplay between the hormonal impact of ovarian function on breast cancer risk, the risk reduction associated with oophorectomy, and the impact of early menopause on other health outcomes, an integrated multidisciplinary approach is required to aid in the increasingly complex decisions faced by women with high inherited risk of developing gynecologic cancers.
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Präventive operative Optionen für Frauen mit einer familiären Brust- und Eierstockkrebsbelastung. MED GENET-BERLIN 2015. [DOI: 10.1007/s11825-015-0046-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Zusammenfassung
Für das familiäre Mamma- und Ovarialkarzinom ist seit der Entdeckung der beiden Hochrisikogene BRCA1 und BRCA2 in den 1990er-Jahren die genetische Testung und die damit einhergehende individuelle Risikobestimmung möglich. In den zurückliegenden 20 Jahren waren im Rahmen der Betreuung von BRCA-Mutationsträgerinnen und ihren Familien die Bestimmung der Inzidenz und des Phänotyps der Karzinome sowie der Nachweis der Effizienz von prophylaktischen Operationen, intensivierter Brustkrebsfrüherkennung und zielgerichteter Therapieverfahren möglich. Dies versetzt uns heute in die Lage, bei Ratsuchenden individuelle Risikokalkulationen durchzuführen und sie im Rahmen nicht direktiver Beratungsgespräche auf dem Weg zu einer informierten und präferenzsensiblen Entscheidung in Bezug auf die Inanspruchnahme risikoadaptierter Präventionsmaßnahmen zu begleiten. Aktuell und zukünftig gilt es die Herausforderungen z. B. im Zusammenhang mit der Zulassung des ersten PARP-Inhibitors sowie mit der Entdeckung neuer Risikogene zu bewältigten. Schwerpunkt dieses Artikels ist der Nachweis, dass v. a. Frauen mit Mutationen in den Hochrisikogenen BRCA1/2 von operativen Maßnahmen profitieren.
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Snyder CL, Casey MJ, Lynch HT. Should risk-reducing surgery in women from hereditary breast ovarian cancer families be confined to removal of the fallopian tubes with ovarian conservation? WOMENS HEALTH 2015; 11:423-7. [PMID: 26246179 DOI: 10.2217/whe.15.26] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Affiliation(s)
- Carrie L Snyder
- Department of Preventive Medicine & Public Health, Creighton University, HLSB Room 202, 2500 California Plaza, Omaha, NE 68178, USA
| | - Murray Joseph Casey
- Department of Preventive Medicine & Public Health, Creighton University, HLSB Room 202, 2500 California Plaza, Omaha, NE 68178, USA.,Department of Obstetrics & Gynecology, Creighton University, Omaha, NE 68178, USA
| | - Henry T Lynch
- Department of Preventive Medicine & Public Health, Creighton University, HLSB Room 202, 2500 California Plaza, Omaha, NE 68178, USA.,Department of Internal Medicine, Creighton University, Omaha, NE 68178, USA
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Walker JL, Powell CB, Chen LM, Carter J, Bae Jump VL, Parker LP, Borowsky ME, Gibb RK. Society of Gynecologic Oncology recommendations for the prevention of ovarian cancer. Cancer 2015; 121:2108-20. [PMID: 25820366 DOI: 10.1002/cncr.29321] [Citation(s) in RCA: 180] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2014] [Revised: 12/22/2014] [Accepted: 01/20/2015] [Indexed: 12/25/2022]
Abstract
Mortality from ovarian cancer may be dramatically reduced with the implementation of attainable prevention strategies. The new understanding of the cells of origin and the molecular etiology of ovarian cancer warrants a strong recommendation to the public and health care providers. This document discusses potential prevention strategies, which include 1) oral contraceptive use, 2) tubal sterilization, 3) risk-reducing salpingo-oophorectomy in women at high hereditary risk of breast and ovarian cancer, 4) genetic counseling and testing for women with ovarian cancer and other high-risk families, and 5) salpingectomy after childbearing is complete (at the time of elective pelvic surgeries, at the time of hysterectomy, and as an alternative to tubal ligation). The Society of Gynecologic Oncology has determined that recent scientific breakthroughs warrant a new summary of the progress toward the prevention of ovarian cancer. This review is intended to emphasize the importance of the fallopian tubes as a potential source of high-grade serous cancer in women with and without known genetic mutations in addition to the use of oral contraceptive pills to reduce the risk of ovarian cancer.
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Affiliation(s)
- Joan L Walker
- Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
| | - C Bethan Powell
- Northern California Gynecologic Cancer Program, Kaiser Permanente San Francisco, San Francisco, California
| | - Lee-May Chen
- Gynecology/Oncology Division, University of California San Francisco/Mt. Zion Cancer Center, San Francisco, California
| | - Jeanne Carter
- Gynecology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York
| | - Victoria L Bae Jump
- Division of Gynecologic Oncology, University of North Carolina, Chapel Hill, North Carolina
| | | | - Mark E Borowsky
- Helen F. Graham Cancer Center, Christiana Care Health System, Newark, Delaware
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Perri T, Lifshitz D, Sadetzki S, Oberman B, Meirow D, Ben-Baruch G, Friedman E, Korach J. Fertility treatments and invasive epithelial ovarian cancer risk in Jewish Israeli BRCA1 or BRCA2 mutation carriers. Fertil Steril 2015; 103:1305-12. [PMID: 25792249 DOI: 10.1016/j.fertnstert.2015.02.011] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2014] [Revised: 02/07/2015] [Accepted: 02/09/2015] [Indexed: 10/23/2022]
Abstract
OBJECTIVE To determine whether BRCA mutation carriers who undergo fertility treatments are at increased risk of developing invasive epithelial ovarian cancer (IEOC). DESIGN Historical cohort study. SETTING Tertiary university-affiliated medical center and the National Cancer Registry. PATIENT(S) A total of 1,073 Jewish Israeli BRCA mutation carriers diagnosed in a single institution between 1995 and 2013, including 164 carriers (15.2%) who had fertility treatments that included clomiphene citrate (n = 82), gonadotropin (n = 69), in vitro fertilization (IVF) (n = 66), or a combination (n = 50), and 909 carriers not treated for infertility. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Odds ratios (OR) and 95% confidence intervals (CI) for IEOC association with fertility treatments and other hormone and reproductive variables. RESULT(S) In 175 (16.3%) mutation carriers, IEOC was diagnosed; 139 women carried BRCA1, 33 carried BRCA2, and 3 had unknown mutations. Fertility treatments were not associated with IEOC risk (age-adjusted OR 0.63; 95% CI, 0.38-1.05) regardless of treatment type (with clomiphene citrate, OR 0.87; 95% CI, 0.46-1.63; with gonadotropin, OR 0.59; 95% CI, 0.26-1.31; with IVF, OR 1.08, 95% CI, 0.57-2.06). Multivariate analysis indicated an increased risk of IEOC with hormone-replacement therapy (OR 2.22; 95% CI, 1.33-3.69) and a reduced risk with oral contraceptives (OR 0.19; 95% CI, 0.13-0.28) in both BRCA1 and BRCA2 mutation carriers. Parity was a risk factor for IEOC by univariate but not multivariate analysis. CONCLUSION(S) According to our results, treatments for infertile BRCA mutation carriers should not be contraindicated or viewed as risk modifiers for IEOC. Parity as a risk factor in BRCA mutation carriers warrants further investigation.
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Affiliation(s)
- Tamar Perri
- Department of Gynecologic Oncology, Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
| | - Dror Lifshitz
- Department of Gynecologic Oncology, Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Siegal Sadetzki
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Cancer and Radiation Epidemiology Unit, Gertner Institute, Sheba Medical Center, Tel Hashomer, Israel
| | - Bernice Oberman
- Cancer and Radiation Epidemiology Unit, Gertner Institute, Sheba Medical Center, Tel Hashomer, Israel
| | - Dror Meirow
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Fertility Preservation Center and IVF Unit, Sheba Medical Center, Tel Hashomer, Israel
| | - Gilad Ben-Baruch
- Department of Gynecologic Oncology, Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Eitan Friedman
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Susanne Levy-Gertner Oncogenetics Unit, Danek Gertner Institute of Human Genetics, Sheba Medical Center, Tel Hashomer, Israel
| | - Jacob Korach
- Department of Gynecologic Oncology, Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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Li DP, Du C, Zhang ZM, Li GX, Yu ZF, Wang X, Li PF, Cheng C, Liu YP, Zhao YS. Breastfeeding and ovarian cancer risk: a systematic review and meta-analysis of 40 epidemiological studies. Asian Pac J Cancer Prev 2015; 15:4829-37. [PMID: 24998548 DOI: 10.7314/apjcp.2014.15.12.4829] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
The present systematic review and meta-analysis was conducted to assess any association between breastfeeding and the risk of ovarian cancer. A systematic search of published studies was performed in PUBMED and EMBASE and by reviewing reference lists from retrieved articles through March 2013. Data extraction was conducted independently by two authors. Pooled relative risk ratios were calculated using random-effect models. Totals of 5 cohort studies and 35 case-control studies including 17,139 women with ovarian cancer showed a 30% reduced risk of ovarian cancer when comparing the women who had breastfed with those who had never breastfed (pooled RR = 0.70, 95% CI: 0.64-0.76; p = 0.00), with significant heterogeneity in the studies (p = 0.00; I2 = 76.29%). A significant decreasd in risk of epithelial ovarian cancer was also observed (pooled RR = 0.68, 95% CI: 0.61-0.76). When the participants were restricted to only parous women, there was a slightly attenuated but still significant risk reduction of ovarian cancer (pooled RR = 0.76, 95% CI: 0.69-0.83). For total breastfeeding duration, the pooled RRs in the < 6 months, 6-12 months and > 12 months of breastfeeding subgroups were 0.85 (95% CI: 0.77-0.93), 0.73 (95% CI: 0.65-0.82) and 0.64 (95%CI: 0.56-0.73), respectively. Meta-regression of total breastfeeding duration indicated an increasing linear trend of risk reduction of ovarian cancer with the increasing total breastfeeding duration (p = 0.00). Breastfeeding was inversely associated with the risk of ovarian cancer, especially long-term breastfeeding duration that demonstrated a stronger protective effect.
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Affiliation(s)
- Da-Peng Li
- Department of Epidemiology, School of Public Health, Harbin Medical University, Harbin, China E-mail : ,
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Daly MB, Dresher CW, Yates MS, Jeter JM, Karlan BY, Alberts DS, Lu KH. Salpingectomy as a means to reduce ovarian cancer risk. Cancer Prev Res (Phila) 2015; 8:342-8. [PMID: 25586903 DOI: 10.1158/1940-6207.capr-14-0293] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2014] [Accepted: 12/29/2014] [Indexed: 12/21/2022]
Abstract
Bilateral salpingo-oophorectomy (BSO) has become the standard-of-care for risk reduction in women at hereditary risk of ovarian cancer. Although this procedure significantly decreases both the incidence of and mortality from ovarian cancer, it affects quality of life, and the premature cessation of ovarian function may have long-term health hazards. Recent advances in our understanding of the molecular pathways of ovarian cancer point to the fallopian tube epithelium as the origin of most high-grade serous cancers (HGSC). This evolving appreciation of the role of the fallopian tube in HGSC has led to the consideration of salpingectomy alone as an option for risk management, especially in premenopausal women. In addition, it is postulated that bilateral salpingectomy with ovarian retention (BSOR), may have a public health benefit for women undergoing benign gynecologic surgery. In this review, we provide the rationale for salpingectomy as an ovarian cancer risk reduction strategy.
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Affiliation(s)
- Mary B Daly
- Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
| | - Charles W Dresher
- Department of Translational Outcomes Research Group of the Translational Research Program of the Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
| | - Melinda S Yates
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Joanne M Jeter
- Department of Medicine, University of Arizona, Tucson, Arizona
| | - Beth Y Karlan
- Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, California
| | | | - Karen H Lu
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas
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