Prevention of Ovarian Cancer

Roberta B. Ness, M.D., M.P.H.,

Chair of the Department of

Epidemiology, University of

Pittsburgh, Graduate School of Public

Health

What Puts Women at Risk?

• Family history of ovarian and breast cancers

• Infertility

• Endometriosis

• Talc use

• Hormone replacement therapy

Does Anything Prevent Ovarian Cancer?

• Oral contraceptives

• Pregnancies

• Breast feeding (long duration)

• Tubal ligation

• Oophorectomy and hysterectomy

Controversies

• NSAIDS

• Fertility drugs

• Androgens

• Diet: fat, coffee

Ovarian Cancer Risk and Protection

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

8% 10%

20%

40%

0%

5%

10%

15%

20%

25%

30%

35%

40%

No affectedrelatives

1 relativeBreast Ca

1 relativeOvarian Ca

1 relativeBreast &

Ovarian Ca

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

30%40%

55%

78%

0%

10%

20%

30%

40%

50%

60%

70%

80%

No affectedrelatives

1 relativeBreast Ca

1 relativeOvarian Ca

1 relativeBreast &

Ovarian Ca

The Legacy of BRCA

BRCA1: Lifetime Risk of Ovarian Cancer:28-66%

BRCA2: Risk by age 50: <1%But by age 70: 27%

Infertility and Ovarian Cancer Risk

Compared to women with 3 or more pregnancies…

RISKWomen with 0 pregnancies

not trying 2.1

Women with 0 pregnanciestrying 4.3

Endometriosis

Risk 1.0

1.9

X 1.7 1.7

X X

Brinton Ness Ness 2000 2002

Hypotheses (New)

• Inflammation: Pelvic inflammation exposes the lining of the ovary to toxic mediators and makes cells quickly turnover. Both may be mutagenic.

Etiologic Hypotheses (New)

Androgens and Progestins

• Androgen exposure elevates risk

• Progestins reduce risk

Talc Use and Ovarian Cancer

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

Pregnancies and Ovarian Cancer

00,10,20,30,40,50,60,70,80,9

1

0 1 2 3 4 5 6

Number of pregnancies

Ris

k

Breast Feeding and Ovarian Cancer

00,10,20,30,40,50,60,70,80,9

1

Number of months breastfeeding

Ris

k

0 6 12 18 24

Tubal Ligation

OophorectomyC

um

ula

tive

Pro

por

tion

wit

hou

t B

reas

t or

B

RC

A-R

elat

ed G

ynec

olog

ic C

ance

r Salpingo-oophorectomy (n=98)

Months0 12 24 36 48 60 72 84

1.0

0.9

0.8

0.7

0.6Surveillance (n=72)

FertilityDrugs

Oral Contraception in Women with

BRCA Mutations or Family HistoryModan (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

Tubal Ligation in BRCA Carriers

1,0

0,4 0,3

0,0

0,2

0,4

0,6

0,8

1,0

No tuballigation

Tubal Tubal +OCs

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

Time.com

Could a Common Painkiller Cut Your Risk of Ovarian Cancer?

health

Thursday March 8, 2001

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)

What Can You (And Yours) Change?

• Oophorectomy after family size completed

• Oral contraceptive use

• Tubal ligation

BRCA Mutation Carriers