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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.: