Cancer Genetics (PowerPoint download)

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					Cancer Genetics
                             Issues
• Colorectal guidelines
   – Awaiting publication of coloproctologists guidance
   – SIGN / QIS update started
• Breast / ovarian
   – Breast MRI
   – Minor changes to guidelines?
      • NF1
      • Average age v absolute ages
      • Incorporate pathology into testing criteria?
   – Change to English guidance?
   – Trials to report – UKFOCSS, FH01 etc
• Other conditions – gastric, renal etc.?
                 Breast cancer
• Breast MRI
• NF1
• English guidelines?
• FH01 study results – confirm effectiveness,
  reduce mortality
• Molecular testing
    – Triple negative young women (<30)
    – High grade serous ovarian cancer?
    – BRCA3 results by Manchester score
    – Double primary breast and ovary - audit
     Proposals from last meeting
• Modify mutation testing to allow pathology
  data to be used where available
• Test ovarian cancers with visceral metastases?,
  or all high grade serous ovarian cancers
  – Meeting of small group with Dr Gourlay
  – Aberdeen d/w NSD funding additional testing
  – Glasgow propose trainee project to assess yield
• Lower threshold if impacts management
  (PARPi) – BRCA3 info
    Ovarian BRCAness meeeting
• Should we test more women with ovarian
  cancer?
  – Visceral mets, young age, response to platinum,
    prolonged survival
  – High grade serous
  – Literature – no ideal series. One publication suggests
    23% of high grade serous have BRCA1 mutation but
    ascertainment / possible founders etc not clarified.
  – Agreed helpful to have further information in our
    population group. ?test for 12 months and look at
    data.
  – Oncologists also interested in somatic mutations
  – Not currently influencing treatment but will in future
      Ovarian BRCAness meeeting
• Practicalities
   – Need family history and pathology info
   – Consent issues
   – Suggest take blood at initial meeting, store until consent
     sorted out.
   – Joint leaflet for patients, standard request / consent form /
     referral form. Refer if positive?
   – ?additional capacity Aberdeen
• Numbers – 350 high grade serous / year?
• Oncology meeting in November
• Audit previous ovarian testing? (? Info to CG)
     Ovarian BRCAness meeeting
• Technical issues
  – ?tumour testing
  – ? Rebiopsy to look for second mutations, mets etc
  – ?other pretest would be useful? RT-PCR, antibody
    stains etc??
      Ovarian cancer in Glasgow
• Robots in molecular lab, improved turnaround
  for BRCA2 dramatically.
• Previously reluctant to consider ovarian
  samples, now willing to consider a trainee
  project
• Store blood from ovarian cancer patients
• If high grade serous / FH / long survival etc,
  refer to genetics to consider testing
                  UKFOCSS
• No longer recruiting
• Scans will end 2011
• No plans to arrange any ongoing screening,
  will leave to gynaecologist
• UCL suggest baseline investigations at first
  appointment, discuss surgery etc
 BRCA3 results by Manchester score
• 618 results. Scores 4-65. 56 mutations (9%), 31
  BRCA1, 25 BRCA2.
• 18 mutations in 446 with score <20. (4%). 3 with
  ovarian FH, of 33 with ovarian history.
• 38 mutations in 172 with score >20. (22%)
• Score of 16+: 47 mutations in 290 (16%) [4%]
• Score of 18+: 44 mutations in 221 (19.9%) [8%]
    Double Primary breast / ovary
• Breast / ovary double primaries
• 57 tested. 54 full results
• 17 BRCA1, 9 BRCA2, 6 VUS found. 46% pickup.
• Manchester score over 20 – 66% pickup
  (22/33)
• Manchester score <20 – 36% detection (4/11)
    Triple negatives / young br ca
• Little data yet! 16 samples tested which say
  triple neg on database. 7 BRCA1 mutations, 2
  BRCA2, 2 VUS. (56%)
• Breast cancer under 30: 18 samples tested, 5
  BRCA1, 2 BRCA2, 1 VUS BRCA2. (44%)
• Additional 4 <30 with p53: bilat breast ca
  under 30, br ca 29 with affected M and MA, br
  ca 29 with relative CACC, br ca 29 with
  osteosarcoma.
                 FH01 study
• 6710 women under 50 at moderately increased
  risk, control group from age trial and Dutch
  series. FU 5 years, annual mammo.
• 136 breast cancers diagnosed, 77% screen
  detected, 21% interval cancers. Tumours smaller,
  less likely node positive, moe fabourable grade.
• Predicted mortality significantly lower. (Prevent
  2.1 breast cancer deaths per 10,000 screens.)
              IMPACT study
• Ready to recruit in Glasgow
• 4 men agreed to take part, 17 BRCA2 positive
  and 12 BRCA2 negative eligible.
• Not yet approached BRCA1 men.
• Lower testing threshold?
• When management shown to be impacted
  – Contralateral mastectomy
  – PARP inhibitor trial results
                   England
• NICE guidance 2004 / 2006
• 1 under 40, 2 first degree relatives any age
• Risk 1.7x population risk, 3% 10 year risk at 40
• Now looking again at this, want to look at
  survival benefit.
• Proposal to look at women with 4x risk, 18
  monthly mammography from 40 to 73. No
  screening for those at lesser degrees of risk.
              Molecular testing
• Young women with triple negative tumours?
  – Management impact?
  – PARP inhibitor trials
  – Contralateral mastectomy
        – Recent paper looking at large series with breast cancer and
          BRCA testing, by age and BRCA status
        – Changed 10 year risk from 6% to 28%
• Incorporation of pathology data –
  – Manchester score: simple to use
  – BOADICEA: complicated to use
                      BRCA1
•   More likely ER-, HER2-
•   Less likely grade 1
•   -4 for HER2+. +4 for grade 3 triple negative
•   Overall sensitivity and specificity increased
•   Suggest testing women <31 with triple
    negative disease for BRCA1, no other groups
    over 10% threshold without family history
       Contralateral mastectomy
• Series of 705 bilateral cases and 1398 unilateral
  controls, from cancer registry in US, cohort of
  52000 diagnosed under 55
• BRCA testing
• 5 and 10 year risks of contralateral breast ca by
  age of first diagnosis
• 28% v 6% at 25-29 y
• 19% v 4% at 40-44y
• 10% v 4% at 50-54y

				
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posted:10/11/2011
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