Skip to main content

Advertisement

SpringerLink
Log in

Risk reducing salpingectomy and delayed oophorectomy in high risk women: views of cancer geneticists, genetic counsellors and gynaecological oncologists in the UK

  • Original Article
  • Published:
Familial Cancer Aims and scope Submit manuscript

Abstract

Risk-reducing-salpingectomy and Delayed-Oophorectomy (RRSDO) is being proposed as a two-staged approach in place of RRSO to reduce the risks associated with premature menopause in high-risk women. We report on the acceptability/attitude of UK health professionals towards RRSDO. An anonymised web-based survey was sent to UK Cancer Genetics Group (CGG) and British Gynaecological Cancer Society (BGCS) members to assess attitudes towards RRSDO. Baseline characteristics were described using descriptive statistics. A Chi square test was used to compare categorical, Kendal-tau-b test for ordinal and Mann–Whitney test for continuous variables between two groups. 173/708 (24.4 %) of invitees responded. 71 % respondents (CGG = 57 %/BGCS = 83 %, p = 0.005) agreed with the tubal hypothesis for OC, 55 % (CGG = 42 %/BGCS = 66 %, p = 0.003) had heard of RRSDO and 48 % (CGG = 46 %/BGCS = 50 %) felt evidence was not currently strong enough for introduction into clinical practice. However, 60 % respondents’ (CGG = 48 %/BGCS = 71 %, p = 0.009) favoured offering RRSDO to high-risk women declining RRSO, 77 % only supported RRSDO within a clinical trial (CGG = 78 %/BGCS = 76 %) and 81 % (CGG = 76 %/BGCS = 86 %) advocated a UK-wide registry. Vasomotor symptoms (72 %), impact on sexual function (63 %), osteoporosis (59 %), hormonal-therapy (55 %) and subfertility (48 %) related to premature menopause influenced their choice of RRSDO. Potential barriers to offering the two-stage procedure included lack of data on precise level of benefit (83 %), increased surgical morbidity (79 %), loss of breast cancer risk reduction associated with oophorectomy (68 %), need for long-term follow-up (61 %) and a proportion not undergoing DO (66 %). There were variations in perception between BGCS/CGG members which are probably attributable to differences in clinical focus/expertise between these two groups. Despite concerns, there is reasonable support amongst UK clinicians to offering RRSDO to premenopausal high-risk women wishing to avoid RRSO, within a prospective clinical trial.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. CRUK (2014) Ovarian cancer, key stats. Cancer statistics. Nov 2014 ed. CRUK: Cancer Research, UK pp 1–2. http://publications.cancerresearchuk.org/downloads/Product/CS_KF_OVARY.pdf

  2. Integrated genomic analyses of ovarian carcinoma (2011) Nature 474(7353):609–615

    Article  Google Scholar 

  3. Alsop K, Fereday S, Meldrum C et al (2012) BRCA mutation frequency and patterns of treatment response in BRCA mutation-positive women with ovarian cancer: a report from the Australian Ovarian Cancer Study Group. J Clin Oncol 30(21):2654–2663

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Pal T, Permuth-Wey J, Betts JA et al (2005) BRCA1 and BRCA2 mutations account for a large proportion of ovarian carcinoma cases. Cancer 104(12):2807–2816

    Article  CAS  PubMed  Google Scholar 

  5. Pennington KP, Walsh T, Harrell MI et al (2014) Germline and somatic mutations in homologous recombination genes predict platinum response and survival in ovarian, fallopian tube, and peritoneal carcinomas. Clin Cancer Res 20(3):764–775

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Walsh T, Casadei S, Lee MK et al (2011) Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing. Proc Natl Acad Sci USA 108(44):18032–18037

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Zhang S, Royer R, Li S et al (2011) Frequencies of BRCA1 and BRCA2 mutations among 1,342 unselected patients with invasive ovarian cancer. Gynecol Oncol 121(2):353–357

    Article  CAS  PubMed  Google Scholar 

  8. Antoniou A, Pharoah PD, Narod S et al (2003) Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet 72(5):1117–1130

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Chen S, Parmigiani G (2007) Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol 25(11):1329–1333

    Article  PubMed Central  PubMed  Google Scholar 

  10. Mavaddat N, Peock S, Frost D et al (2013) Cancer risks for BRCA1 and BRCA2 mutation carriers: results from prospective analysis of EMBRACE. J Natl Cancer Inst 105(11):812–822

    Article  CAS  PubMed  Google Scholar 

  11. Chen S, Iversen ES, Friebel T et al (2006) Characterization of BRCA1 and BRCA2 mutations in a large United States sample. J Clin Oncol 24(6):863–871

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. King MC, Marks JH, Mandell JB (2003) Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science 302(5645):643–646

    Article  CAS  PubMed  Google Scholar 

  13. Marroni F, Aretini P, D’Andrea E et al (2004) Penetrances of breast and ovarian cancer in a large series of families tested for BRCA1/2 mutations. Eur J Hum Genet 12(11):899–906

    Article  CAS  PubMed  Google Scholar 

  14. Rennert G, Dishon S, Rennert HS, Fares F (2005) Differences in the characteristics of families with BRCA1 and BRCA2 mutations in Israel. Eur J Cancer Prev 14(4):357–361

    Article  CAS  PubMed  Google Scholar 

  15. Evans DG, Shenton A, Woodward E, Lalloo F, Howell A, Maher ER (2008) Penetrance estimates for BRCA1 and BRCA2 based on genetic testing in a clinical cancer genetics service setting: risks of breast/ovarian cancer quoted should reflect the cancer burden in the family. BMC Cancer 8:155

    Article  PubMed Central  PubMed  Google Scholar 

  16. Jacobs I (2005) Screening for familial ovarian cancer: the need for well-designed prospective studies. J Clin Oncol 23(24):5443–5445

    Article  PubMed  Google Scholar 

  17. Evans DG, Gaarenstroom KN, Stirling D et al (2009) Screening for familial ovarian cancer: poor survival of BRCA1/2 related cancers. J Med Genet 46(9):593–597

    Article  CAS  PubMed  Google Scholar 

  18. Hermsen BB, Olivier RI, Verheijen RH et al (2007) No efficacy of annual gynaecological screening in BRCA1/2 mutation carriers; an observational follow-up study. Br J Cancer 96(9):1335–1342

    PubMed Central  CAS  PubMed  Google Scholar 

  19. Rebbeck TR, Kauff ND, Domchek SM (2009) Meta-analysis of risk reduction estimates associated with risk-reducing salpingo-oophorectomy in BRCA1 or BRCA2 mutation carriers. J Natl Cancer Inst 101(2):80–87

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Lokkegaard E, Jovanovic Z, Heitmann BL, Keiding N, Ottesen B, Pedersen AT (2006) The association between early menopause and risk of ischaemic heart disease: influence of hormone therapy. Maturitas 53(2):226–233

    Article  CAS  PubMed  Google Scholar 

  21. Rivera CM, Grossardt BR, Rhodes DJ et al (2009) Increased cardiovascular mortality after early bilateral oophorectomy. Menopause 16(1):15–23

    Article  PubMed Central  PubMed  Google Scholar 

  22. Michelsen TM, Pripp AH, Tonstad S, Trope CG, Dorum A (2009) Metabolic syndrome after risk-reducing salpingo-oophorectomy in women at high risk for hereditary breast ovarian cancer: a controlled observational study. Eur J Cancer 45(1):82–89

    Article  PubMed  Google Scholar 

  23. Rivera CM, Grossardt BR, Rhodes DJ, Rocca WA (2009) Increased mortality for neurological and mental diseases following early bilateral oophorectomy. Neuroepidemiology 33(1):32–40

    Article  PubMed Central  PubMed  Google Scholar 

  24. Rocca WA, Bower JH, Maraganore DM et al (2007) Increased risk of cognitive impairment or dementia in women who underwent oophorectomy before menopause. Neurology 69(11):1074–1083

    Article  CAS  PubMed  Google Scholar 

  25. Rocca WA, Bower JH, Maraganore DM et al (2008) Increased risk of parkinsonism in women who underwent oophorectomy before menopause. Neurology 70(3):200–209

    Article  CAS  PubMed  Google Scholar 

  26. Madalinska JB, Hollenstein J, Bleiker E et al (2005) Quality-of-life effects of prophylactic salpingo-oophorectomy versus gynecologic screening among women at increased risk of hereditary ovarian cancer. J Clin Oncol 23(28):6890–6898

    Article  PubMed  Google Scholar 

  27. Madalinska JB, van Beurden M, Bleiker EM et al (2006) The impact of hormone replacement therapy on menopausal symptoms in younger high-risk women after prophylactic salpingo-oophorectomy. J Clin Oncol 24(22):3576–3582

    Article  PubMed  Google Scholar 

  28. Rocca WA, Grossardt BR, de Andrade M, Malkasian GD, Melton LJ 3rd (2006) Survival patterns after oophorectomy in premenopausal women: a population-based cohort study. Lancet Oncol 7(10):821–828

    Article  PubMed  Google Scholar 

  29. Manchanda R, Burnell M, Abdelraheim A et al (2012) Factors influencing uptake and timing of risk reducing salpingo-oophorectomy in women at risk of familial ovarian cancer: a competing risk time to event analysis. BJOG 119(5):527–536

    Article  CAS  PubMed  Google Scholar 

  30. Crum CP, Drapkin R, Kindelberger D, Medeiros F, Miron A, Lee Y (2007) Lessons from BRCA: the tubal fimbria emerges as an origin for pelvic serous cancer. Clin Med Res 5(1):35–44

    Article  PubMed Central  PubMed  Google Scholar 

  31. Dietl J, Wischhusen J, Hausler SF (2011) The post-reproductive fallopian tube: better removed? Hum Reprod 26(11):2918–2924

    Article  CAS  PubMed  Google Scholar 

  32. Leblanc E, Narducci F, Farre I et al (2011) Radical fimbriectomy: a reasonable temporary risk-reducing surgery for selected women with a germ line mutation of BRCA 1 or 2 genes? rationale and preliminary development. Gynecol Oncol 121(3):472–476

    Article  PubMed  Google Scholar 

  33. Kim SH, Frey MK, Blank SV (2014) Occult tubal carcinoma found at risk reducing salpingectomy in a BRCA1 carrier. Gynecol Oncol Rep 9:1–2

    Article  Google Scholar 

  34. Greene MH, Mai PL, Schwartz PE (2011) Does bilateral salpingectomy with ovarian retention warrant consideration as a temporary bridge to risk-reducing bilateral oophorectomy in BRCA1/2 mutation carriers? Am J Obstet Gynecol 204(1):19 e1–19 e6

    Article  Google Scholar 

  35. Miller SM, Roussi P, Daly MB, Scarpato J (2010) New strategies in ovarian cancer: uptake and experience of women at high risk of ovarian cancer who are considering risk-reducing salpingo-oophorectomy. Clin Cancer Res 16:5094–5106

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. Domchek SM, Friebel TM, Singer CF et al (2010) Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. JAMA, J Am Med Assoc 304(9):967–975

    Article  CAS  Google Scholar 

  37. Heemskerk-Gerritsen BA, Seynaeve C, van Asperen CJ, et al.(2015) Breast cancer risk after salpingo-oophorectomy in healthy BRCA1/2 mutation carriers: revisiting the evidence for risk reduction. J Natl Cancer Inst 107(5). doi:10.1093/jnci/djv033

  38. Kauff ND, Domchek SM, Friebel TM et al (2008) Risk-reducing salpingo-oophorectomy for the prevention of BRCA1- and BRCA2-associated breast and gynecologic cancer: a multicenter, prospective study. J Clin Oncol 26(8):1331–1337

    Article  PubMed Central  PubMed  Google Scholar 

  39. Eisen A, Lubinski J, Klijn J et al (2005) Breast cancer risk following bilateral oophorectomy in BRCA1 and BRCA2 mutation carriers: an international case-control study. J Clin Oncol 23(30):7491–7496

    Article  PubMed  Google Scholar 

  40. Antoniou AC, Pharoah PD, Narod S et al (2005) Breast and ovarian cancer risks to carriers of the BRCA1 5382insC and 185delAG and BRCA2 6174delT mutations: a combined analysis of 22 population based studies. J Med Genet 42(7):602–603

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  41. Easton DF, Ford D, Bishop DT (1995) Breast and ovarian cancer incidence in BRCA1-mutation carriers. breast cancer linkage consortium. Am J Hum Genet 56(1):265–271

    PubMed Central  CAS  PubMed  Google Scholar 

  42. Ford D, Easton DF, Stratton M et al (1998) Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. the breast cancer linkage consortium. Am J Hum Genet 62(3):676–689

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  43. Arts-de Jong M, Harmsen MG, Hoogerbrugge N, Massuger LF, Hermens RP, de Hullu JA (2015) Risk-reducing salpingectomy with delayed oophorectomy in BRCA1/2 mutation carriers: patients’ and professionals’ perspectives. Gynecol Oncol 136(2):305–310

    Article  PubMed  Google Scholar 

  44. Holman LL, Friedman S, Daniels MS, Sun CC, Lu KH (2014) Acceptability of prophylactic salpingectomy with delayed oophorectomy as risk-reducing surgery among BRCA mutation carriers. Gynecol Oncol 133(2):283–286

    Article  PubMed Central  PubMed  Google Scholar 

  45. Flesken-Nikitin A, Hwang CI, Cheng CY, Michurina TV, Enikolopov G, Nikitin AY (2013) Ovarian surface epithelium at the junction area contains a cancer-prone stem cell niche. Nature 495(7440):241–245

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  46. Dubeau L (2008) The cell of origin of ovarian epithelial tumours. Lancet Oncol 9(12):1191–1197

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  47. Powell CB (2014) Risk reducing salpingo-oophorectomy for BRCA mutation carriers: twenty years later. Gynecol Oncol 132(2):261–263

    Article  PubMed  Google Scholar 

  48. Kwon JS, Tinker A, Pansegrau G et al (2013) Prophylactic salpingectomy and delayed oophorectomy as an alternative for BRCA mutation carriers. Obstet Gynecol 121(1):14–24

    Article  PubMed  Google Scholar 

  49. Grann VR, Patel P, Bharthuar A et al (2010) Breast cancer-related preferences among women with and without BRCA mutations. Breast Cancer Res Treat 119(1):177–184

    Article  PubMed  Google Scholar 

  50. Schrag D, Hanger M (2007) Medical oncologists’ views on communicating with patients about chemotherapy costs: a pilot survey. J Clin Oncol 25(2):233–237

    Article  PubMed  Google Scholar 

  51. Grava-Gubins I, Scott S (2008) Effects of various methodologic strategies: survey response rates among Canadian physicians and physicians-in-training. Can Fam Physician 54(10):1424–1430

    PubMed Central  PubMed  Google Scholar 

  52. Kroth PJ, McPherson L, Leverence R (2009) Combining web-based and mail surveys improves response rates: a PBRN study from PRIME Net. Ann Fam Med 7(3):245–248

    Article  PubMed Central  PubMed  Google Scholar 

  53. Leece P, Bhandari M, Sprague S et al (2004) Internet versus mailed questionnaires: a controlled comparison (2). J Med Internet Res 6(4):e39

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

We are grateful to the President of the BGCS, the Chair of the CGG and the members of their executive committees for their support of the survey. We thank members of the BGCS IT subcommittee for their valuable comments on the survey. This work is supported by researchers at the National Institute for Health Research University College London Hospitals Biomedical Research Centre.

Author contribution

R.M. and D.C. prepared the initial draft of the survey. All authors contributed to the development of the survey. R.M., D.C. and U.M. were involved in conducting the survey, data collection and analysis. R.M. and D.C. prepared the first draft of the manuscript. All authors critically contributed to and revised the manuscript and approved the final version.

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynaecology, Northampton General Hospital, Northampton, UK

    Dhivya Chandrasekaran

  2. Department of Women’s Cancer, EGA Institute for Women’s Health, Gynaecological Cancer Research Centre, University College London, First Floor, Maple House, 149 Tottenham Court Road, London, W1T 7DN, UK

    Usha Menon & Ranjit Manchanda

  3. Department of Genetic Medicine, St Mary’s Hospital, Manchester, UK

    Gareth Evans

  4. Department of Gynaecological Oncology, Addenbrookes Hospital, Cambridge, UK

    Robin Crawford

  5. Department of Gynaecology, University College London Hospital, London, UK

    Ertan Saridogan & Davor Jurkovic

  6. Department of Clinical Genetics, Guys Hospital, London, UK

    Chris Jacobs

  7. Department of Medical Genetics, University of Cambridge, Addenbrookes Hospital, Cambridge, UK

    Marc Tischkowitz

  8. Centre for Experimental Cancer Medicine, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London, UK

    Elly Brockbank & Ranjit Manchanda

  9. Department of Gynaecological Oncology, Bartshealth NHS Trust, Royal London Hospital, 10th Floor, South Block, Whitechapel Road, London, E1 1BB, UK

    Jatinder Kalsi & Ranjit Manchanda

Authors
  1. Dhivya Chandrasekaran
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Usha Menon
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gareth Evans
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Robin Crawford
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ertan Saridogan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Chris Jacobs
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Marc Tischkowitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Elly Brockbank
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jatinder Kalsi
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Davor Jurkovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Ranjit Manchanda
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ranjit Manchanda.

Ethics declarations

Conflict of interest

U.M. has a financial interest in Abcodia, Ltd, a company formed to develop academic and commercial development of biomarkers for screening and risk prediction. The other authors declare no conflict of interest.

Ethical approval

This project was submitted to the Research Ethics committee at the University College London Hospital Joint R&D office. Under the Research Governance Framework the project was deemed to fall under audit or service development and permission for data collection, analysis and submission for publication was given.

Funding

This work has not been directly funded by any commercial organisation, or charity.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 64 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chandrasekaran, D., Menon, U., Evans, G. et al. Risk reducing salpingectomy and delayed oophorectomy in high risk women: views of cancer geneticists, genetic counsellors and gynaecological oncologists in the UK. Familial Cancer 14, 521–530 (2015). https://doi.org/10.1007/s10689-015-9823-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10689-015-9823-y

Keywords

Search

Navigation