Dr Matt Hewitt

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Dr Matt Hewitt

• Prophylactic Bilateral Salpingoophorectomy

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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

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• 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)

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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

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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

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Stage at diagnosis and 5 year survival
Uterus Cervix Ovary
FIGO Staging
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Why not screen the population for ovarian cancer?
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Screening

• The process by which unrecognised diseases or
  defects are identified by tests that can be
  applied rapidly on a large scale

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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

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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
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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
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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).
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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

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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)

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Ovarian CancerScreening
BSO candidates

• 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 lt60 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

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Symptoms following risk reducing BSO in
hereditary breast and ovarian cancer

• More palpatations
• More constipation
• More pain and stiffness
• More musculoskeletal
• Lower levels of depression
• Lower levels of mental distress

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Risk reducing strategies for BRCA 1 and BRCA 2

• 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 lt40 years
• COCP decreases risk of ovarian cancer (slight
  increase risk of breast cancer)
• COCP decreases risk of Endometrial cancer

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HRT following hysterectomy and BSO for HNPCC

• 25 of endometrial cancers in premenopausal women
• No evidence of detriment in women of low grade
  and stage in taking HRT

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HRT risks
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HRT following BSO for BRCA 1 BRCA2

• Majority 68of 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

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Thank you