Transcript Surgical risk-reduction with Familial Gynae Cancers

Familial
Gynaecological Cancers
A/Prof Andreas Obermair
Gynaecological Oncologist
RBWH, Greenslopes Private Hospital
www.obermair.info
Major Known Mutations
•
•
•
•
BRCA1
BRCA2
Mismatch Repair Genes
Other undiscovered
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
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
HPNCC/mismatch repair genes
• Most have colon cancer penetrance of 3070%
• Endometrial Ca 42%
– Annual Uterine sampling &Transvaginal
Ultrasound
– Hysterectomy at time of colectomy
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
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
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
• 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%)
Kauff et al. Risk reducing salpingo-oophorectomy in
women with BRCA1 or BRCA2 mutation.
N.Eng.J.Med.346(2002),pp 1609-1615
• 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
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
• 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
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 surgery
• Risks of laparotomy ~ 17%
• Risks of laparoscopy ~ 4%
Elit et al . Prophylactic oophorectomy in Ontario.
Fam.
Cancer 1 (2001),pp. 143-148
• Ontario Hospital based study 41
institutions prophylactic BSO from 19921998
• 274 pts (141 co-existent gynae problems)
• 15.7% complications –bleeding, infection,
damage to organs - most laparotomy
Krauf et al. Risk reducing salpingooophorectomy in women with BRCA1 or BRCA2
mutations. N.Eng.J.Med.346(2002),pp. 1609-1615
• 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
• Menopause
–
–
–
–
lipid profile
2x CAD
Osteoporosis
Higher rate of decreased libido & sexual
satisfaction
• Role of HRT
Surgical Options
• Minimum 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.397-403
Role of Hysterectomy
• ? Increased risk of endometrial Ca
• Hysterectomy guarantees complete
resection of fallopian tube
• HRT simplified
But increased morbidity
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
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)
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 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
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
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
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
www.obermair.info
07 3830 5824