Dr Matt Hewitt

Prophylactic Bilateral Salpingoophorectomy

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

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)

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

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

0

20

40

60

80

100

1 2 3 4

Stage at diagnosis and 5 year survival

Uterus

Cervix

Ovary

FIGO Staging

Why not screen the population for ovarian cancer?

Screening

“The process by which unrecognised

diseases or defects are identified by tests

that can be applied rapidly on a large

scale”

WHO Screening CriteriaDisease

• 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

Sensitivity of 100%Sensitivity of 100%

Positive predictive value of 94% for ovarian cancerPositive predictive value of 94% for ovarian cancer

But incidence of ovarian cancer in this population was 50%But incidence of ovarian cancer in this population was 50%

In real population incidence is 50 per 100,000In real population incidence is 50 per 100,000

Minimum suggested PPV value of an ovarian cancer screening test is 10%Minimum suggested PPV value of an ovarian cancer screening test is 10%

i.e. 9 negative laparotomy / oscopy for 1 ovarian cancer diagnosisi.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 If sensitivity of test is only 90% a specificity of 99.6% must be obtained to achieve a 10% PPVachieve a 10% PPV

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).

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

Family history

• Lifetime risk 1 in 70

• 1 x 1st degree relative 1 in 20 (5%)

• 2 x 1st degree relative 1 in 14 (7%)

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

• 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

• 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

• 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

HRT risks

• 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

Thank you