1. Prevention of Ovarian Cancer Roberta B. NessRoberta B. Ness, M.D., M.P.H., Chair of the Department of Epidemiology, University of Pittsburgh, Graduate School of Public Health

2. What Puts Women at Risk? Family history of ovarian and breast cancers Infertility Endometriosis Talc use Hormone replacement therapy

3. Does Anything Prevent Ovarian Cancer? Oral contraceptives Pregnancies Breast feeding (long duration) Tubal ligation Oophorectomy and hysterectomy

4. Controversies NSAIDS Fertility drugs Androgens Diet: fat, coffee

5. Ovarian Cancer Risk and Protection

6. Probability of a 50 yo Non-Jewish Woman with Ovarian Cancer Carrying a BRCA1 Mutation

7. Probability of a 50 yo Jewish Woman with Ovarian Cancer Carrying a BRCA1 Mutation

8. The Legacy of BRCA BRCA1: Lifetime Risk of Ovarian Cancer: 28-66% BRCA2: Risk by age 50: <1% But by age 70: 27%

9. Infertility and Ovarian Cancer Risk Compared to women with 3 or more pregnancies… RISK Women with 0 pregnancies not trying2.1 Women with 0 pregnancies trying4.3

10. Endometriosis Risk 1.0 1.9 X 1.7 X Brinton Ness Ness 2000 2002

11. Hypotheses (New) Inflammation: Pelvic inflammation exposes the lining of the ovary to toxic mediators and makes cells quickly turnover. Both may be mutagenic.

12. Etiologic Hypotheses (New) Androgens and Progestins Androgen exposure elevates risk Progestins reduce risk

13. Talc Use and Ovarian Cancer

14. Oral Contraceptives and Ovarian Cancer Risk 30-40%  Longer use, more protection Protection 20 or more years after last use New OCs protective May be best:low estrogen high progestin

15. Pregnancies and Ovarian Cancer

16. Breast Feeding and Ovarian Cancer 06 121824

17. Tubal Ligation

18. Oophorectomy Cumulative Proportion without Breast or BRCA-Related Gynecologic Cancer Salpingo- oophorectomy (n=98) Months 0 12 24 36 48 607284 1.0 0.9 0.8 0.7 0.6 Surveillance (n=72)

19. Fertility Drugs

20. Oral Contraception in Women with BRCA Mutations or Family History Modan (2001) Women without mutations protected Women with mutations not protected Narod (1998) All women with or without BRCA mutations protected Walker (2002) All women with or without family history protected

21. Tubal Ligation in BRCA Carriers

22. Aspirin Use Tzonou Cramer Rosenberg Tavani Akhmed Moysich 1984 1998 2000 2000 2001 2001 Risk 1.0 0.9 0.9 0.75 X X X 0.7 0.6 0.5 X X X khanov

23. Time.com Could a Common Painkiller Cut Your Risk of Ovarian Cancer? health Thursday March 8, 2001

24. What Can You (and Yours) Change? Anyone Oral Contraceptive Use Pregnancies and Breast Feeding Tubal Ligation Don’t Use Talc Don’t Use HRT (except for perimenopausal symptoms)

25. What Can You (And Yours) Change? Oophorectomy after family size completed Oral contraceptive use Tubal ligation BRCA Mutation Carriers