1. Dr Matt Hewitt Prophylactic Bilateral Salpingoophorectomy

2. Ovarian Familial screening BRCA1 40-60% risk of Ovarian Ca BRCA2 15-20% risk Ovarian Ca HNPCC ( hMLH1 hMSH2) Tissue needed from affected individual to localise the gene mutation Not always available - family tree Ethical issues with informing other family members

3. HNPCC 60% life tme risk of bowel cnacer 40% life time risk endometrial cancer 12% life time risk of ovarian cnacer Cancers tend to be 2 decades earlier tha background OK to consider short course of HRT (possible benfit of reducing bowel cancer risk)

4. Ovarian cancer Lifetime risk 1 in 70 90% are epithelial tumours 75% present at late stage III/IV 5 – 10 % Hereditary predisposition BRCA I and II HNPCC

5. Ovarian cancer Lifetime 1.6% BRCA1 – 35-60% ave age 50 years BRCA2 - 12 -25% ave age 60 years Increased survival and higer seneitivity to platimum base drugs HNPCC – bowel 30-40%, endometrial 40-50% and ovarian 8-10% ave age 42 years

9. Stage at diagnosis and 5 year survival Uterus Cervix Ovary FIGO Staging

10. Why not screen the population for ovarian cancer?

11. Screening “The process by which unrecognised diseases or defects are identified by tests that can be applied rapidly on a large scale”

12. WHO Screening Criteria Disease serious high prevalence of preclinical stage natural history understood long lead time Diagnostic test sensitive and specific simple and cheap safe and acceptable reliable Diagnosis & Treatment facilities are adequate effective, acceptable, safe treatment available

14. Sensitivity of 100% Positive predictive value of 94% for ovarian cancer But incidence of ovarian cancer in this population was 50% In real population incidence is 50 per 100,000

15. Minimum suggested PPV value of an ovarian cancer screening test is 10% i.e. 9 negative laparotomy / oscopy for 1 ovarian cancer diagnosis If sensitivity of test is only 90% a specificity of 99.6% must be obtained to achieve a 10% PPV

16. Lead time bias By screening, the intention is to diagnose a disease earlier than it would be without screening. Without screening, the disease may be discovered later once symptoms appear. Even if in both cases a person will die at the same time, because we diagnosed the disease early with screening, the survival time since diagnosis is longer with screening. No additional life has been gained (and indeed, there may be added anxiety as the patient must live with knowledge of the disease for longer).

17. UKTOCS 200,000 women 50 to 74 years of age Group 1 – serial Ca125 levels Group 2 – Yearly TVS if abnormal Ca125 Group 3 – Control group - no screening

18. Family history Lifetime risk 1 in 70 1 x 1 st degree relative 1 in 20 (5%) 2 x 1 st degree relative 1 in 14 (7%)

19. Ovarian CancerScreening Proven BRCA1 BRCA2 hMLH1 hMSH2 Two or more 1st or 2nd degree relatives with ovarian Ca One 1st or 2nd degree relative with ovarian Ca, plus one or more 1st or 2nd degree relatives with breast Ca <60 yrs old One 1st or 2nd degree relative with both breast and ovarian Ca 1st /2nd degree relative with ovarian Ca plus two 1st or 2nd degree relatives with Ca colon BSO candidates

20. More palpatations More constipation More pain and stiffness More musculoskeletal Lower levels of depression Lower levels of mental distress Symptoms following risk reducing BSO in hereditary breast and ovarian cancer

21. BSO reduces risk of ovarian (still remaining risk of primary peritoneal cancer) BSO decreases risk of breast cancer by 50% In general population and in BRCA 1 and 2 greatest benefit in women <40 years COCP decreases risk of ovarian cancer (slight increase risk of breast cancer) COCP decreases risk of Endometrial cancer Risk reducing strategies for BRCA 1 and BRCA 2

22. 25% of endometrial cancers in premenopausal women No evidence of detriment in women of low grade and stage in taking HRT HRT following hysterectomy and BSO for HNPCC

23. HRT risks

24. Majority 68%of BRCA associated breast cancers are not ER or PR +ve No increase in receptor +ve breast cancers who had BSO and who were on HRT 1 study suggested lower risk of breast cancer after BSO while on HRT Short course of HRT after BSO is beneficial Dose of HRT is much lower than natural levels Women with history of hormonal breast cancer should not take HRT as does increase risk of new breast cancers HRT following BSO for BRCA 1 BRCA2

25. Thank you