Hereditary Cancer syndromes Flashcards
BRCA mutations
- Autosomal dominant genetic mutations that increase the risk of cancer development including breast and Ovarian cancer
BrRCA 1 risks
- Located chromosome 17
- 60% Breast
-40% Ovarian
Background Cancer Risks
Lifetime risks of cancer by the age of 70 years
- Breast:12%
- Ovarian 1,2%
BRCA 2 risks
- Located Chromosome 13
- Breast: 40%
- Ovarian 20%
Other cancer risks with BRCA
- Primary peritoneal cancer
- Tubal Cancer
- Male Breast cancer
- Prostate cancer
Screening for BRCA
- Screening should be offered via a familial cancer centre with counselling about implications of diagnosing carrier status
NB History findings that may indicate need for screening - Many patients with likely familial cancer do not have an identifiable BRCA mutation
- Assess family pedigree for affected individuals and age of diagnosis
- Assess for Ashkenazi Jewish ancestry
- FRA-BOC calculator can be used to assess a patient’s family cancer history and advise about the need for referral to a familial cancer centre
- Generally carrier testing should begin with an affected individual
o If a mutation is detected, then predictive testing for that specific mutation can be offered to relatives
Management of Known BRCA mutation carrier wrt Breast cancer risk
o Modifiable risk factors
- Advise to stop smoking
- Advise to maintain healthy weight
- Advise to limit alcohol intake
- Encourage breastfeeding
o Screening
- Encourage self-examination regularly
- Annual breast examinations starting at age 25 years
- Annual mammogram (+/- USS/MRI) starting age 35 years or 5 years earlier than youngest affected family member
o Risk-reducing surgery
- Bilateral mastectomy
* Reduces breast cancer risk by 90%
- Bilateral oophorectomy
* Reduces breast cancer risk by 50% if done before age 40
Management of diagnosis of BRCA mutation wrt ovarian cancer
o Modifiable risk factors
- cOCP use may be protective in those wanting to preserve fertility
o Screening
- No screening program has been shown to reduce the risk of ovarian cancer
o Risk-reducing surgery
- Bilateral salpingo-oophorectomy – 90% reduction in risk
* BRCA 1: Recommend at age 35-40 years, or 10 years before earliest familial onset (when childbearing completed)
* BRCA 2: Age 45-50 acceptable as tend to have later onset
* 5% risk of occult malignancy at time of BSO
Lynch syndrome definition
autosomal dominant cancer susceptibility syndrome
Cancer risks associated with Lynch Syndrome
- Increased risk of
o Colorectal cancer 30-50%
o Endometrial cancer - 50% lifetime risk
- Mean age 50 years
o Ovarian cancer - 10% lifetime risk
- Mean age 45 years
o Stomach cancer
o Small bowel cancer
o Pancreatic and liver cancer
o Urinary tract and kidney cancer - Absolute cancer risk 80%
- Diagnosis by Amsterdam Criteria: the 3-2-1 rule
o 3: or more relatives with Lynch cancers
o 2: generations affected
o 1: cancer in person aged <50 years - Genetic testing
o Should be done through a familial cancer centre
o Testing of a family member who has developed a Lynch syndrome cancer
o Predictive testing for that specific mutation in other family members can then be offered
Management of Lynch syndrome Carrier
- Referral to familial cancer centre
- Counselling on symptoms that should prompt review (AUB, pain, weight loss)
- Screening
o No evidence to support TV ultrasound, endometrial sampling or ovarian cancer screening
o Annual colonoscopy, urine cytology and skin checks from age 25 - Chemoprophylaxis
o cOCP recommended as 50% risk reduction in ovarian cancer - Risk-reducing surgery
o TAH/BSO - >95% reduction in endometrial and ovarian cancer risk
o Perform around age 35 once childbearing complete or after treatment for colorectal cancer
o Pre-operative TV USS/endometrial sampling and Ca-125 recommended
o Can give oestrogen HRT as breast cancer risk not significant - Counselling about inheritance and risk to offspring
