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Primary Peritoneal Cancer, Fallopian Tube Cancer685U85U HNPCC(Lynch Syndrome Type II)  Microsatillite DNA sequences which are prone to mutation during replication HNPCC & endometrial cancer Rare: Urological tumours MSH2 & MLH1 genes most commonly implicated$  < k  + HPNCC/mismatch repair genes Most have colon cancer penetrance of 30-70% Endometrial Ca 42% Annual Uterine sampling &Transvaginal Ultrasound Hysterectomy at time of colectomy &?T?Tb   7   $     Cancer Gene Testing in Qld("  Qld Clinical Genetics Service established in 1995 Funding for 50 tests per year Uses software to estimate individuals with a risk >15% May not detect all predisposing mutations Requires a blood sample from an affected living relative<PZcZ9ZPc9"  Hereditary Ovarian Cancer 4 Cohort studies (2 retrospective, 2 prospective) 1 family history only, 3 BRCA mutations All 4 studies found protective effect of surgery Variability in patient populations & patient methodology L"  Rebbeck et al. The Prevention and Observation of Surgical end points Study Group. Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations. N.Eng.J.Med. 346(2002),pp.1616-1622< X   M Retrospective cohort of 259 women with BSO and 292 no BSO (matched control group) BSO group  6 cases of stage 1 ovarian ca 2 cases of peritoneal ca found 3.8&8.6 yrs later No BSO  58 ovarian ca (8.8yrs median follow-up) Only 6 stage 1(11%)||10i 1  zKauff et al. Risk reducing salpingo-oophorectomy in women with BRCA1 or BRCA2 mutation. N.Eng.J.Med.346(2002),pp 1609-1615{{<   J Prospective 98 BSO vs. 72 who chose not to have BSO 2 groups similar age & other risk factors Mean follow-up 25.4 months BSO  1 peritoneal Ca (16.3 months) No BSO  4 ovarian Ca 8 breast Ca, 1 peritoneal Ca _9_!  Piver et al. Familial Ovarian Cancer.A report of 658 families from the Gilda Radner Familial Ovarian Cancer Registry 1981-1991. Cancer 71(1993) pp582-588< H  F 324 women (familial ovarian cancer registry) with family history of 2 or more 1st or 2nd degree relatives with ovarian Ca All patients had prophylactic BSO 6 women primary peritoneal Ca (1.9%) Residual risk of Primary Peritoneal Cancern i  +Summary Prophylactic Surgery(Risk of ovarian cancer reduced by > 95% Most patients found at stage 1 (prognosis ) Risk of breast cancer reduced by 50% Risk of occult cancer found at surgery 14 to 18% Residual risk of primary peritoneal cancer < 2% (/+*Risks of surgery3Risks of laparotomy ~ 17% Risks of laparoscopy ~ 4%44(  gElit et al . Prophylactic oophorectomy in Ontario. Fam. Cancer 1 (2001),pp. 143-148 6h2  V       1 Ontario Hospital based study 41 institutions prophylactic BSO from 1992-1998 274 pts (141 co-existent gynae problems) 15.7% complications  bleeding, infection, damage to organs - most laparotomy<f  M     |Krauf et al. Risk reducing salpingo-oophorectomy in women with BRCA1 or BRCA2 mutations. N.Eng.J.Med.346(2002),pp. 1609-1615,}Y#<   L 98 BSO - complications 4 1 re-operation for small bowel obstruction Increasing trend to laparoscopy with risk of complications 0.22-4.0%  Long-term adverse effects( pMenopause lipid profile 2x CAD Osteoporosis Higher rate of decreased libido & sexual satisfaction Role of HRT L Y  Y p  Surgical Options YMinimum of BSO Occult ovarian or fallopian tube Ca Fallopian tube and Infundibulo-Pelvic Ligament need to be removed completely. Age? Uncommon in women < 35 years Peritoneal lavage for cytology 35 women, 3 + cytology 1occult fallopian tube Ca, 1 fallopian ACIS 1 no histological evidence of Ca Coglan et al. Gynecol Oncol. 85(2002), pp.397-403ZZZZMZ2Zs"M  G   ^  r        Role of Hysterectomy ? Increased risk of endometrial Ca Hysterectomy guarantees complete resection of fallopian tube HRT simplified But increased morbidityp Benefits on Breast Cancer )Prophylactic BSO protective for breast Ca RR 0.47(95% CI 0.29-0.77) HRT did not negate the reduction in breast Ca Rebbeck et al Natl. Cancer Inst. 91(1999) pp1475-1479 Proportion Breast Ca free at 5 yr 94% BSO group 79% surveillance group(p=0.07) Kauff et al N.Engl.J.Med. 346(2002),pp 1609-1615 r6#-11.6#-1  Hr    , Alternative to oophorectomy("   Oral contraceptives - Controversies 60% reduction in Ovarian Cancer if used for >6yrs Narod et al. N.Engl.J.Med.339(1998) No reduction in study in Israel But small study & wide confidence limits Modan et al. N.Eng.J.Med. 345(2001)$2$ )$$2 )     HV  h   Tubal Ligation0    Associated with decreased incidence in general population (?reason) BRCA1 Tubal ligation in 232 assoc with odds ratio of 0.39 (95% confidence limits 0.22-0.70) Tubal ligation & OCP 0.28 (95% confidence limits 0.15-0.52) Narod et al. Lancet. 357(2001)pp.1467-1470 l+~$" J    J    .  & +Perceptions of women with BRCA1/2 Mutations,,$+ zPsychological testing on those with surgery vs. observation, Anxiety reduced with surgery, 86% high level of satisfaction.:{=$$)$$z  Discussion  No randomized control trials of surgery vs. observation Cohorts studies showed risk reduction Complications are low (note impact of laparoscopic surgery) Optimal procedure is not well defined Fallopian tube ca Role OCP & tubal ligation\0Z20Z20Z2t$&&$$<     Conclusions  Women with family history should be assessed for genetic counseling & possible testing Surgery - ovary + fall. tube MUST BE removed Young women (< 35 years) >> ?role of OCP+/- tubal ligation 0 <tEH        ` ` ̙33` 333MMM` ff3333f` f` f` 3>?" dd@,|?" dd@   " @ ` n?" dd@   @@``PR    @ ` ` p>> D<(    6 P  T Click to edit Master title style! !  0H   RClick to edit Master text styles Second level Third level Fourth level Fifth level!     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(q Oh+'0 `h    (4Surgical risk-reduction with Familial Gynae Cancers Dr Perrinis Justin Gough-re14tMicrosoft PowerPointon @0/6@zU@@9V s"Gg  W *  --- @ !0---- @ !,0---- @ ! \---- @ !|---- @ !---- @ !---- @ !---- @ !---- @ ! ---- @ !---- @ ! ---- @ !---- @ ! ---- @ !  ---- @ ! )---- @ ! 5---- @ ! @---- @ ! I---- @ ! R---- @ ! [---- @ ! f---- @ ! o---- @ ! x---- @ ! ---- @ !---- @ !---- @ ! ---- @ ! ---- @ ! ---- @ !---- @ ! ---- @ ! ---- @ !---- @ ! ---- @ !---- @ ! ---- @ ! ---- @ ! ---- @ ! --~-- @ !--|-- @ ! --z-- @ ! --x-- @ ! %--v-- @ ! .--t-- @ ! 9--r-- @ ! B--p-- @ ! N--n-- @ ! Z--l-- @ !e--j-- @ ! t--h-- @ !--f-- @ !--d-- @ !--b-- @ !--`-- @ !--^-- @ ! ---'@Times New Roman-. 2 } Familial )"6!."Systemhi-@Times New Roman-. 2 Gynaecological4"%!"!"!.-@Times New Roman-. 2 aCancers/"%.-@Times New Roman-. *2 A/Prof Andreas Obermair(#( ,/.-@Times New Roman-. 2 Gynaecological"   .-@Times New Roman-. 2 ! Oncologist#  .-@Times New Roman-. 2 ARBWH, ," .-@Times New Roman-. 2 A. Greenslopesc" .-@Times New Roman-. 2 A!Private Hospital  #  .-@Times New Roman-. !2 8www.obermair.infoe  $  .---%}--'՜.+,D՜.+,     .On-screen Show Dr PerrinSh^:A Times New RomanSymbol WebdingsDefault Design!Familial Gynaecological CancersMajor Known MutationsHereditary Ovarian CancerHNPCC(Lynch Syndrome Type II)HPNCC/mismatch repair genes Cancer Gene Testing in QldHereditary Ovarian CancerRebbeck et al. The Prevention and Observation of Surgical end points Study Group. Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations. N.Eng.J.Med. 346(2002),pp.1616-1622{Kauff et al. Risk reducing salpingo-oophorectomy in women with BRCA1 or BRCA2 mutation. N.Eng.J.Med.346(2002),pp 1609-1615Piver et al. Familial Ovarian Cancer.A report of 658 families from the Gilda Radner Familial Ovarian Cancer Registry 1981-1991. Cancer 71(1993) pp582-588Summary Prophylactic SurgeryRisks of surgeryhElit et al . Prophylactic oophorectomy in Ontario. Fam. Cancer 1 (2001),pp. 143-148 }Krauf et al. Risk reducing salpingo-oophorectomy in women with BRCA1 or BRCA2 mutations. N.Eng.J.Med.346(2002),pp. 1609-1615Long-term adverse effectsSurgical OptionsRole of HysterectomyBenefits on Breast CancerAlternative to oophorectomyTubal Ligation,Perceptions of women with BRCA1/2 Mutations Discussion Conclusions Slide 24  Fonts UsedDesign Template Slide Titles 8@ _PID_HLINKSAlhttp://www.obermair.info/$_q 0Justin GoughJustin Gough  !"#$%&'()*+,-./0123456789:;<=>?@ABCDEFGHIJKLMNOPQRSTUVWXYZ[\]^_`abcdefghijklmnopqrstuvwxyz{|}~      !"#$%&'()*+-./012356789:;@Root EntrydO)PicturesCurrent User4SummaryInformation( PowerPoint Document(qDocumentSummaryInformation8,