British Gynaecological Cancer Society (BGCS) ovarian, tubal and primary peritoneal cancer guidelines: Recommendations for practice update 2024

Recommendations are graded as per the Royal College of Obstetricians and Gynaecologists document, Clinical Governance Advice No. 1: Guidance for the Development of RCOG Green-top Guidelines, available on the RCOG website at (see Supplementary Tables 1 and 2 below and at www.rcog.org.uk/rcog). Definitions for certainty of evidence based on formal GRADE assessment within systematic reviews are given in Supplementary Table 3 [682GRADE Handbook.: GRADE Working Group; 2013. Available from: https://gdt.gradepro.org/app/handbook/handbook.html#h.svwngs6pm0f2.Google Scholar]. This guideline is for healthcare professionals who care for women, non-binary and trans people with different types of tubo-ovarian cancer. Within this document we use the terms woman and women's health. However, it is important to acknowledge that it is not only women for whom it is necessary to access women's health and reproductive services in order to maintain their gynaecological health and reproductive wellbeing. Gynaecological services and delivery of care must therefore be appropriate, inclusive and sensitive to the needs of those individuals whose gender identity does not align with the sex they were assigned at birth [1Gribble KD, Bewley S, Bartick MC, Mathisen R, Walker S, Gamble J, et al. Effective Communication About Pregnancy, Birth, Lactation, Breastfeeding and Newborn Care: The Importance of Sexed Language. Frontiers in Global Women's Health. 2022;3.Google Scholar]. The guideline development process is detailed below:•Chair, officers, council and guidelines committee (GC) nominated a lead for each guideline topic;•Lead then identified a team called the guideline team (GT) to develop the 1st draft;•1st draft was submitted to the GC;•GC approved draft and recommended changes;•Changes were accepted by the GT who produced the guidelines;•2nd draft was then submitted to council members and officers;•Council and officers approved 2nd draft and recommended changes;•Changes were then accepted by GC and GT;•3rd draft was sent to BGCS membership, national and international peer review and to public consultation, including relevant charities and patient support groups;•GT then made changes based on peer review comments;•Final draft approved by council and officers. Ovarian cancer remains the 6th most common cancer in females in the UK with 7,495 new cases annually (2016–18), equating to a lifetime risk of 1 in 50 UK females [2Ovarian Cancer Statistics [Internet]. 2017 [cited 09.02.2022]. Available from: https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/ovarian-cancer.Google Scholar]. The crude all-age incidence rate is 22.8/100,000 (2016–18). However, changes in the age of the population at diagnosis has resulted in the peak age incidence rising from 60-64 years to 75–79 years. Ovarian cancer incidence rates have been falling over the past decade, with the greatest fall being seen in the 60 to 69-year-old population, falling from 60.7/100,000 in 2001–3, to 46.7/100,000 in 2016–18. No clear differences have been identified in incidence with deprivation [3Cancer Intelligence Team at Cancer Research UK. Based on method reported in National Cancer Intelligence Network Cancer by Deprivation in England Incidence, 1996-2010 Mortality, 1997-2011(link is external) . Using cancer incidence data 2013-2017 (Public Health England) and population data 2013-2017 (Office for National Statistics) by Indices of Multiple Deprivation 2015 income domain quintile, cancer type, sex, and five-year age band. 2020.Google Scholar]. The incidence of ovarian cancer appears to be lower in Asian, Black and Mixed/Multiple ethnicity populations as compared to the White ethnic group [4Delon C. Brown K.F. Payne N.W.S. Kotrotsios Y. Vernon S. Shelton J. Differences in cancer incidence by broad ethnic group in England, 2013–2017.Br J Cancer. 2022; 126: 1765-1773Crossref PubMed Scopus (32) Google Scholar]. Along with changing incidence rates, ovarian cancer mortality has also changed over time. The peak age for ovarian cancer mortality is 85–89 years, and nearly half of all ovarian cancer deaths occur in patients over the age of 75 years (2017–19). Mortality rates have decreased by 23 % over the past five decades, and have accelerated in the past few years and are now at 12.2/100,000 for 2017–19, equating to 4142 deaths annually (2017–19), and are projected to fall even further [5Smittenaar C.R. Petersen K.A. Stewart K. Moitt N. Cancer incidence and mortality projections in the UK until 2035.Br J Cancer. 2016; 115: 1147-1155Crossref PubMed Scopus (347) Google Scholar]. The greatest fall in mortality rates is seen in the age 60–69-year age group, from 42.2/100,000 (1988–90) to 24.5/100,000 (2017–19). Many factors have been reported to contribute to the changing ovarian cancer landscape, for example increasing contraception use, risk-reducing surgery and evolving treatment options; these will be discussed in the subsequent chapters. There is a great need for accurate Cancer Registry data, without which it would not be possible to explore and understand the trends in ovarian cancer care within the UK as exemplified in the BGCS, Target Ovarian Cancer and Ovarian Cancer Action NCRAS Ovarian Cancer Audit Feasibility Pilot [6Ovarian Cancer Audit Feasibility Pilot Study Group Ovarian Cancer Audit Feasibility Pilot. Disease Profile in England: Incidence, mortality, stage and survival for ovary, fallopian tube and primary peritoneal carcinomas. Public Health England, London2020 10 Jan 2020Google Scholar]. Recommendations There is currently no role for screening women considered at low or population level risk of development of ovarian cancer. (Grade A) The role of ovarian cancer surveillance in women at high risk of ovarian cancer has shown good performance characteristics and significant downstaging. However, there is no available information demonstrating a survival benefit. Although surveillance is not an alternative to risk-reducing surgery in high risk women, there may be a potential role for considering four-monthly surveillance using a longitudinal biomarker algorithm, as an interim risk management strategy in women delaying risk-reducing surgery, following careful counselling. (Grade C) Women who carry a pathogenic or likely pathogenic variant in a high to moderate risk ovarian cancer susceptibility gene (BRCA1, BRCA2, RAD51C, RAD51D, BRIP1, PALB2) should be offered informed counselling for bilateral risk-reducing salpingo-oophorectomy (RRSO) for ovarian cancer prevention, once their family is complete. (Grade A) Women with Lynch syndrome should be offered risk-reducing surgery in the form of a bilateral salpingo-oophorectomy and total hysterectomy to reduce their risk of ovarian and endometrial cancer. The timing of surgery should be individualised, based on the gene-specific risk, once their family is complete. (Grade A) Risk-reducing early salpingectomy and delayed oophorectomy (RRESDO) as a two-stage surgical prevention procedure in women at increased risk of ovarian cancer should only be undertaken within the context of a research trial. (Grade C) Women with a lifetime risk of ovarian cancer equal to or above 4–5 % can be offered surgical prevention in the form of bilateral risk reducing salpingo-oophorectomy (RRSO). (Grade B) All women being offered surgical prevention should be reviewed by a specialist, with the support of a multidisciplinary team, to discuss risk reducing surgery. (Grade B) A SEE-FIM protocol should be used for histopathological assessment for women undergoing RRSO. (Grade A) Women diagnosed with a STIC or invasive cancer on histology should be referred to a specialist gynaecological cancer MDT for consideration of treatment options. (Grade A) If isolated STIC is diagnosed at bilateral early salpingectomy alone, cytology is negative and imaging normal, completion bilateral oophorectomy is strongly advised. (Grade C) For women undergoing prophylactic oophorectomy, consideration should be given to HRT, and consultation of the joint BGCS/British Menopause Society guidelines is recommended. Women without a personal history of breast cancer (or contra-indications to the use of HRT) who undergo risk-reducing surgery that leads to an iatrogenic menopause should be offered HRT till the average age of the natural menopause. Maintaining HRT compliance is necessary to minimise the detrimental consequences of premature menopause. (Grade B). HRT is usually contraindicated in women with a personal history of breast cancer and should avoided in women with ER + or PR + breast cancer. (Grade B) Some women at increased risk of ovarian cancer may not be at increased risk of breast cancer (e.g. BRIP1/Lynch syndrome). HRT use beyond the age of the natural menopause in these women may be governed by the same principles as women at population-based risk. (Grade C). Opportunistic bilateral salpingectomy may be considered at the time of intra-abdominal surgery for women who have completed their family. (Grade C) Women undergoing opportunistic salpingectomy should be recruited to prospective studies with long-term follow up. (Grade D) The aim of a screening program is to identify individuals with a condition, or at an increased risk of a condition or health problem, at a time point whereby a timely intervention can be offered to make informed decisions to improve health outcomes [7Shieh Y. Eklund M. Sawaya G.F. Black W.C. Kramer B.S. Esserman L.J. Population-based screening for cancer: hope and hype.Nat Rev Clin Oncol. 2016; 13: 550-565Crossref PubMed Scopus (96) Google Scholar]. Screening can be universal, whereby an ill-defined population (for example females over a certain age) is enrolled or can be case finding in which only those with defined risk factors are screened [8Moyer VA, Force USPST. Screening for cervical cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2012;156(12):880-91, W312.Google Scholar]. The principles of a screening programme were formalised by Wilson and Jungner in 1968 [9Wilson J.M. Jungner Y.G. Principles and practice of mass screening for disease.Bol Oficina Sanit Panam. 1968; 65: 281-393PubMed Google Scholar]. The UK National Screening Committee (UK NSC) have also established clear criteria and guidance for evaluating a population screening program [10UK National Screening Committee. Criteria for a population screening programme United Kingdom: UK National Screening Committee 2022 [Available from: https://www.gov.uk/government/publications/evidence-review-criteria-national-screening-programmes/criteria-for-appraising-the-viability-effectiveness-and-appropriateness-of-a-screening-programme.Google Scholar]. Twin studies suggest that inherited genetic factors contribute around 22 % towards ovarian cancer risk [11Lichtenstein P. Holm N.V. Verkasalo P.K. Iliadou A. Kaprio J. Koskenvuo M. et al.Environmental and heritable factors in the causation of cancer–analyses of cohorts of twins from Sweden, Denmark, and Finland.N Engl J Med. 2000; 343: 78-85Crossref PubMed Scopus (3354) Google Scholar]. BRCA1/BRCA2 genes account for most of the known inheritable component of risk of ovarian cancer. Around 15–22 % of ovarian cancers are caused by pathogenic or likely pathogenic variants (called 'pathogenic variants' or 'PVs') in cancer susceptibility genes (CSGs) [12Walsh T. Casadei S. Lee M.K. Pennil C.C. Nord A.S. Thornton A.M. et al.Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing.Proc Natl Acad Sci U S A. 2011; 108: 18032-18037Crossref PubMed Scopus (775) Google Scholar, 13Chandrasekaran D. Sobocan M. Blyuss O. Miller R.E. Evans O. Crusz S.M. et al.Implementation of Multigene Germline and Parallel Somatic Genetic Testing in Epithelial Ovarian Cancer: SIGNPOST Study.Cancers (Basel). 2021; 13Crossref Scopus (26) Google Scholar]. These include BRCA1, BRCA2, RAD51C, RAD51D, BRIP1, PALB2 and MMR (mismatch repair) genes. Together these PVs account for up to 40 % of the inheritable component of ovarian cancer risk. However, these data are from majority Caucasian populations. Lynch syndrome, an inherited deficiency within the mismatch repair system, also leads to an increased lifetime risk of ovarian cancer [14Ryan N.A. McMahon R.F. Ramchander N.C. Seif M.W. Evans D.G. Crosbie E.J. Lynch syndrome for the gynaecologist.Obstet Gynaecol. 2021; 23: 9-20Crossref PubMed Google Scholar], and it is the second most common hereditary cause of ovarian cancer being associated with around 0.5–2 % of cases [15Crosbie E.J. Ryan N.A.J. McVey R.J. Lalloo F. Bowers N. Green K. et al.Assessment of mismatch repair deficiency in ovarian cancer.J Med Genet. 2021; 58: 687-691Crossref PubMed Scopus (13) Google Scholar, 16Pal T. Akbari M.R. Sun P. Lee J.H. Fulp J. Thompson Z. et al.Frequency of mutations in mismatch repair genes in a population-based study of women with ovarian cancer.Br J Cancer. 2012; 107: 1783-1790Crossref PubMed Scopus (65) Google Scholar]. Of note, the biology of Lynch syndrome-associated ovarian cancer is different and it is often diagnosed at an earlier stage and may be less likely to metastasise [17Ryan N.A.J. Evans D.G. Green K. Crosbie E.J. Pathological features and clinical behavior of Lynch syndrome-associated ovarian cancer.Gynecol Oncol. 2017; 144: 491-495Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar]. A list of common CSGs associated with ovarian cancer risk are summarised in Table 1. In addition to moderate/high penetrance CSGs, a number of common genetic variants called SNPs may be associated with ovarian cancer risk with odds ratios (OR) varying from 0.8 to 1.4. Around 36 validated SNPs have been identified for ovarian cancer through Genome-wide association studies (GWAS). These explain around 6 % of heritability of ovarian cancer [18Kar S.P. Berchuck A. Gayther S.A. Goode E.L. Moysich K.B. Pearce C.L. et al.Common Genetic Variation and Susceptibility to Ovarian Cancer: Current Insights and Future Directions.Cancer Epidemiol Biomarkers Prev. 2018; 27: 395-404Crossref PubMed Scopus (29) Google Scholar]. Multiple SNPs can be combined into a polygenic risk score (PRS) which can be used to refine risk stratification, both in general population women and in women with high-risk CSGs, leading to improved risk estimation and more informed decision making with respect to targeted prevention [19Barnes D.R. Rookus M.A. McGuffog L. Leslie G. Mooij T.M. Dennis J. et al.Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants.Genet Med. 2020; 22: 1653-1666Abstract Full Text Full Text PDF PubMed Scopus (81) Google Scholar, 20Dareng E.O. Tyrer J.P. Barnes D.R. Jones M.R. Yang X. Aben K.K.H. et al.Polygenic risk modeling for prediction of epithelial ovarian cancer risk.Eur J Hum Genet. 2022; 30: 349-362Crossref PubMed Scopus (21) Google Scholar, 21Lee A. Yang X. Tyrer J. Gentry-Maharaj A. Ryan A. Mavaddat N. et al.Comprehensive epithelial tubo-ovarian cancer risk prediction model incorporating genetic and epidemiological risk factors.J Med Genet. 2022; 59: 632-643Crossref PubMed Scopus (30) Google Scholar, 22Pearce C.L. Stram D.O. Ness R.B. Stram D.A. Roman L.D. Templeman C. et al.Population distribution of lifetime risk of ovarian cancer in the United States.Cancer Epidemiol Biomarkers Prev. 2015; 24: 671-676Crossref PubMed Google Scholar]. Having a family history of ovarian cancer is a strong factor affecting ovarian cancer risk. Having a first degree relative (FDR) with epithelial ovarian cancer can increase the risk of developing ovarian cancer by around threefold [23Jervis S. Song H. Lee A. Dicks E. Tyrer J. Harrington P. et al.Ovarian cancer familial relative risks by tumour subtypes and by known ovarian cancer genetic susceptibility variants.J Med Genet. 2014; 51: 108-113Crossref PubMed Scopus (50) Google Scholar]. Higher relative risks are reported for women with two or three FDRs with ovarian cancer [24Sutcliffe S. Pharoah P.D. Easton D.F. Ponder B.A. Ovarian and breast cancer risks to women in families with two or more cases of ovarian cancer.Int J Cancer. 2000; 87: 110-117Crossref PubMed Scopus (0) Google Scholar]. Epigenetics too may play a role in the future. Recently, a DNA methylation signature obtained from cervical cells has been shown to predict future ovarian cancer risk [25Barrett J.E. Jones A. Evans I. Reisel D. Herzog C. Chindera K. et al.The DNA methylome of cervical cells can predict the presence of ovarian cancer.Nat Commun. 2022; 13: 448Crossref PubMed Scopus (18) Google Scholar].Table 1Cancer susceptibility genes, cancer risks, and recommended risk reducing surgery.GeneOvarian Cancer risk (CI)Breast Cancer riskEndometrial Cancer riskRecommended risk reducing surgeryAge of surgery (years)EvidenceReference(s)HBOC or HOCBRCA1High 44 % (36–53 %)HighRRSO≥35-40Strong26Kuchenbaecker K.B. Hopper J.L. Barnes D.R. Phillips K.A. Mooij T.M. Roos-Blom M.J. et al.Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers.JAMA. 2017; 317: 2402-2416Crossref PubMed Scopus (1791) Google ScholarBRCA2High 17 % (11–25 %)HighRRSO≥40Strong26Kuchenbaecker K.B. Hopper J.L. Barnes D.R. Phillips K.A. Mooij T.M. Roos-Blom M.J. et al.Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers.JAMA. 2017; 317: 2402-2416Crossref PubMed Scopus (1791) Google ScholarPALB2Moderate∼5% (2–10 %)HighRRSO>45–50Moderate27Yang X. Leslie G. Doroszuk A. Schneider S. Allen J. Decker B. et al.Cancer Risks Associated With Germline PALB2 Pathogenic Variants: An International Study of 524 Families.J Clin Oncol. 2020; 38: 674-685Crossref PubMed Scopus (260) Google ScholarRAD51CModerate- High 11 % (6–21 %)ModerateRRSO>45Strong28Yang X. Song H. Leslie G. Engel C. Hahnen E. Auber B. et al.Ovarian and Breast Cancer Risks Associated With Pathogenic Variants in RAD51C and RAD51D.J Natl Cancer Inst. 2020; 112: 1242-1250Crossref PubMed Scopus (102) Google ScholarRAD51DModerate- High 13 % (7–23 %)ModerateRRSO>45Strong28Yang X. Song H. Leslie G. Engel C. Hahnen E. Auber B. et al.Ovarian and Breast Cancer Risks Associated With Pathogenic Variants in RAD51C and RAD51D.J Natl Cancer Inst. 2020; 112: 1242-1250Crossref PubMed Scopus (102) Google Scholar#ATMLow3–4 %ModerateNot recommendedNAInsufficient29Lu H.M. Li S. Black M.H. Lee S. Hoiness R. Wu S. et al.Association of Breast and Ovarian Cancers With Predisposition Genes Identified by Large-Scale Sequencing.JAMA Oncol. 2019; 5: 51-57Crossref PubMed Scopus (129) Google Scholar, 30Lilyquist J. LaDuca H. Polley E. Davis B.T. Shimelis H. Hu C. et al.Frequency of mutations in a large series of clinically ascertained ovarian cancer cases tested on multi-gene panels compared to reference controls.Gynecol Oncol. 2017; 147: 375-380Abstract Full Text Full Text PDF PubMed Scopus (95) Google Scholar, 31Kurian A.W. Hughes E. Handorf E.A. Gutin A. Allen B. Hartman A.R. et al.Breast and Ovarian Cancer Penetrance Estimates Derived From Germline Multiple-Gene Sequencing Results in Women.JCO Precis Oncol. 2017; 1: 1-12Crossref PubMed Scopus (113) Google Scholar, 32Norquist B.M. Harrell M.I. Brady M.F. Walsh T. Lee M.K. Gulsuner S. et al.Inherited Mutations in Women With Ovarian Carcinoma.JAMA Oncol. 2016; 2: 482-490Crossref PubMed Google ScholarBRIP1Moderate 6–8 %LowRRSO>45Strong33Ramus SJ, Song H, Dicks E, Tyrer JP, Rosenthal AN, Intermaggio MP, et al. Germline Mutations in the BRIP1, BARD1, PALB2, and NBN Genes in Women With Ovarian Cancer. J Natl Cancer Inst. 2015;107(11).Google ScholarLynch SyndromeMLH1Moderate- High11% (7.4–19.7 %)HighRRSO and Hysterectomy>35–40Strong34Moller P. Prospective Lynch Syndrome Database (PLSD) - cumulative risk for cancer by age, genetic variant, and gender 2019 [Available from: http://www.lscarisk.org/.Google Scholar, 35Moller P. Seppala T.T. Bernstein I. Holinski-Feder E. Sala P. Gareth Evans D. et al.Cancer risk and survival in path_MMR carriers by gene and gender up to 75 years of age: a report from the Prospective Lynch Syndrome Database.Gut. 2018; 67: 1306-1316Crossref PubMed Scopus (382) Google Scholar†MSH2High 17.4 % (11.8–31.2 %)HighRRSO and Hysterectomy>35–40Strong34Moller P. Prospective Lynch Syndrome Database (PLSD) - cumulative risk for cancer by age, genetic variant, and gender 2019 [Available from: http://www.lscarisk.org/.Google Scholar, 35Moller P. Seppala T.T. Bernstein I. Holinski-Feder E. Sala P. Gareth Evans D. et al.Cancer risk and survival in path_MMR carriers by gene and gender up to 75 years of age: a report from the Prospective Lynch Syndrome Database.Gut. 2018; 67: 1306-1316Crossref PubMed Scopus (382) Google ScholarMSH6Moderate- High10.8 % (3.7–38.6 %)HighRRSO and Hysterectomy>35–40Strong34Moller P. Prospective Lynch Syndrome Database (PLSD) - cumulative risk for cancer by age, genetic variant, and gender 2019 [Available from: http://www.lscarisk.org/.Google Scholar, 35Moller P. Seppala T.T. Bernstein I. Holinski-Feder E. Sala P. Gareth Evans D. et al.Cancer risk and survival in path_MMR carriers by gene and gender up to 75 years of age: a report from the Prospective Lynch Syndrome Database.Gut. 2018; 67: 1306-1316Crossref PubMed Scopus (382) Google Scholar*PMS2Low 3 % (0.5–––43.3 %)ModerateHysterectomy only*>45–50Moderate34Moller P. Prospective Lynch Syndrome Database (PLSD) - cumulative risk for cancer by age, genetic variant, and gender 2019 [Available from: http://www.lscarisk.org/.Google Scholar, 35Moller P. Seppala T.T. Bernstein I. Holinski-Feder E. Sala P. Gareth Evans D. et al.Cancer risk and survival in path_MMR carriers by gene and gender up to 75 years of age: a report from the Prospective Lynch Syndrome Database.Gut. 2018; 67: 1306-1316Crossref PubMed Scopus (382) Google ScholarFamily history or model based risk>4–5 %LowLowRRSO≥50Strong / Moderate23Jervis S. Song H. Lee A. Dicks E. Tyrer J. Harrington P. et al.Ovarian cancer familial relative risks by tumour subtypes and by known ovarian cancer genetic susceptibility variants.J Med Genet. 2014; 51: 108-113Crossref PubMed Scopus (50) Google Scholar, 24Sutcliffe S. Pharoah P.D. Easton D.F. Ponder B.A. Ovarian and breast cancer risks to women in families with two or more cases of ovarian cancer.Int J Cancer. 2000; 87: 110-117Crossref PubMed Scopus (0) Google Scholar, 32Norquist B.M. Harrell M.I. Brady M.F. Walsh T. Lee M.K. Gulsuner S. et al.Inherited Mutations in Women With Ovarian Carcinoma.JAMA Oncol. 2016; 2: 482-490Crossref PubMed Google ScholarHBOC: history of breast and ovarian cancer; HOC; history of ovarian cancer; RRSO: risk-reducing salpingo-oophorectomy.*Routine bilateral salpingo oophorectomy is not recommended in women with PMS2 as these women are at low risk of ovarian cancer. However, opportunistic BSO may be considered at time of hysterectomy in post-menopausal women after careful counselling or pros can cons if surgery is undertaken after menopause.#Risks associated with ATM on its own lie below the current thresholds for surgical prevention and RRSO is not currently recommended. Family history plays an important part in decision making. Cases with a family history of ovarian cancer should be discussed with a specialist with greater expertise.†EPCAM deletion can result in silencing of the MSH2 gene. It is hypothesized that ovarian cancer and endometrial risks may be similar to MSH2 carriers but this is dependent on the type of EPCAM deletion. These cases should be discussed on an individual basis with a clinical geneticist, to confirm whether the variant is associated with increased endometrial cancer/ovarian cacner risks.In cases where ovarian cancer risk assessment appears complex or difficult, it is important that advice from a specialist with greater expertise like a clinical geneticist or gynaecologist/gynae-oncologist with special interest in genetic risk assessment or hereditary cancer risk management is sought. Open table in a new tab HBOC: history of breast and ovarian cancer; HOC; history of ovarian cancer; RRSO: risk-reducing salpingo-oophorectomy. *Routine bilateral salpingo oophorectomy is not recommended in women with PMS2 as these women are at low risk of ovarian cancer. However, opportunistic BSO may be considered at time of hysterectomy in post-menopausal women after careful counselling or pros can cons if surgery is undertaken after menopause. #Risks associated with ATM on its own lie below the current thresholds for surgical prevention and RRSO is not currently recommended. Family history plays an important part in decision making. Cases with a family history of ovarian cancer should be discussed with a specialist with greater expertise. †EPCAM deletion can result in silencing of the MSH2 gene. It is hypothesized that ovarian cancer and endometrial risks may be similar to MSH2 carriers but this is dependent on the type of EPCAM deletion. These cases should be discussed on an individual basis with a clinical geneticist, to confirm whether the variant is associated with increased endometrial cancer/ovarian cacner risks. In cases where ovarian cancer risk assessment appears complex or difficult, it is important that advice from a specialist with greater expertise like a clinical geneticist or gynaecologist/gynae-oncologist with special interest in genetic risk assessment or hereditary cancer risk management is sought. Environmental factors that increase the number of lifetime ovulations are considered risk factors for ovarian cancer [36Reid B.M. Permuth J.B. Sellers T.A. Epidemiology of ovarian cancer: a review.Cancer Biol Med. 2017; 14: 9-32Crossref PubMed Scopus (994) Google Scholar]. These include nulliparity, early menarche and late menopause. Factors that reduce ovulation, such as oral contraceptives, have been shown to reduce ovarian cancer risk [37Wu A.H. Pearce C.L. Lee A.W. Tseng C. Jotwani A. 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Blaakaer J. et al.Pelvic inflammatory disease and risk of invasive ovarian cancer and ovarian borderline tumors.Cancer Causes Control. 2013; 24: 1459-1464Crossref PubMed Scopus (34) Google Scholar, 49Rasmussen C.B. Jensen A. Albieri V. Andersen K.K. Kjaer S.K. Increased risk of borderline ovarian tu