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Familial Gynaecological Cancers

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Presentation on theme: "Familial Gynaecological Cancers"— Presentation transcript:

1 Familial Gynaecological Cancers
A/Prof Andreas Obermair Gynaecological Oncologist RBWH, Greenslopes Private Hospital

2 Major Known Mutations BRCA1 BRCA2 Mismatch Repair Genes
Other undiscovered

3 Hereditary Ovarian Cancer
BRCA1 life-time risk 16-54% BRCA2 life-time risk 10-25% Risks vary depending on the population being studied ~10% of cancer due to these genes ? Primary Peritoneal Cancer, Fallopian Tube Cancer

4 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

5 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

6 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

7 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

8 BSO group – 6 cases of stage 1 ovarian ca
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 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%)

9 98 BSO vs. 72 who chose not to have BSO
Kauff et al. Risk reducing salpingo-oophorectomy in women with BRCA1 or BRCA2 mutation. N.Eng.J.Med.346(2002),pp 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

10 All patients had prophylactic BSO 6 women primary peritoneal Ca (1.9%)
Piver et al. Familial Ovarian Cancer.A report of 658 families from the Gilda Radner Familial Ovarian Cancer Registry Cancer 71(1993) pp 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 Cancer

11 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%

12 Risks of surgery Risks of laparotomy ~ 17% Risks of laparoscopy ~ 4%

13 274 pts (141 co-existent gynae problems)
Elit et al . Prophylactic oophorectomy in Ontario. Fam. Cancer 1 (2001),pp Ontario Hospital based study 41 institutions prophylactic BSO from 274 pts (141 co-existent gynae problems) 15.7% complications –bleeding, infection, damage to organs - most laparotomy

14 1 re-operation for small bowel obstruction
Krauf et al. Risk reducing salpingo-oophorectomy in women with BRCA1 or BRCA2 mutations. N.Eng.J.Med.346(2002),pp 98 BSO - complications 4 1 re-operation for small bowel obstruction Increasing trend to laparoscopy with risk of complications %

15 Long-term adverse effects
Menopause lipid profile 2x CAD Osteoporosis Higher rate of decreased libido & sexual satisfaction Role of HRT

16 Surgical Options Minimum of BSO Peritoneal lavage for cytology
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

17 Role of Hysterectomy ? Increased risk of endometrial Ca
Hysterectomy guarantees complete resection of fallopian tube HRT simplified But increased morbidity

18 Benefits on Breast Cancer
Prophylactic BSO protective for breast Ca RR 0.47(95% CI ) HRT did not negate the reduction in breast Ca Rebbeck et al Natl. Cancer Inst. 91(1999) pp 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

19 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)

20 Tubal Ligation Associated with decreased incidence in general population (?reason) BRCA1 Tubal ligation in 232 assoc with odds ratio of 0.39 (95% confidence limits ) Tubal ligation & OCP 0.28 (95% confidence limits ) Narod et al. Lancet. 357(2001)pp

21 Perceptions of women with BRCA1/2 Mutations
Psychological testing on those with surgery vs. observation, Anxiety reduced with surgery, 86% high level of satisfaction. Tiller et al.: Gynecol Oncol 2002

22 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

23 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


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