Risk Management for Female BRCA 1 Mutation Carrier

Familial breast and ovarian cancer predisposition due to a germline mutation in the BRCA1 gene is an autosomal dominant condition.

This risk management guideline has been developed for individuals who have NOT been diagnosed with a relevant cancer/tumour.

It also excludes

high risk breast cancer family with uninformative BRCA result or no DNA testing available
high risk breast and ovarian cancer family with uninformative BRCA result or no DNA testing available

Cancer	BRCA1 carrier up to the age of 70 yrs	General population up to the age of 85 yrs
Breast	57% Residual lifetime risk is dependent on age at consultation	11%
Ovarian/fallopian tube/ primary peritoneal	40% Residual lifetime risk is dependent on age at consultation	1.2%
Primary peritoneal (post RRSO)	<2%	<1%
Pancreatic	May be increased	1.3%

Estimation of cancer risk and age penetrance varies according to different populations assessed. Factors which influence risk include age of onset of the proband, family history and whether the proband had unilateral or bilateral breast cancer. No clinically relevant modifier genes for BRCA1 associated cancers have been identified.

Cancer Management Guidelines

Breast

Surveillance
Individualised screening may be required if there has been a breast cancer diagnosed 35 years and younger.

Recommended Screening

Start at 30 years
Annual MRI’s and mamograms (with or without Ultra sound scans as determined by the specialist) between 30 and 50 years
Annual mammograms (with or without ultra sounds) 50 years and onwards

Contraindications: Pregnancy but ultra sound scans can be considered

Risk Reducing Medications
Tamoxifen and raloxifene have been found to reduce breast cancer risk in unaffected high risk women but there are risks and benefits to this and it is not suited for everyone. Careful discussion with a medical professional is required.

Bilateral risk reducing mastectomy at 40 or younger confers the greatest reduction in risk by at least 90%. The total risk reduction is dependent on the type of surgery.

Breast self awareness should continue post surgery.

Ovary

Surveillance

Do not offer Ca125 or TVS

For asymptomatic women, annual transvaginal ultrasound (TVS) and serum CA125 levels have poor sensitivity and specificity for ovarian cancer. They do not reliably detect ovarian cancers at an early stage, nor do they affect outcomes. This is true of women in the general population and women at high risk of hereditary ovarian cancer. Effective ovarian cancer risk management relies on RRSO.

Surgery
Recommend RRBSO after family completion or by age 40 yrs with peritoneal lavage and close histological examination to exclude occult malignancy.

RRBSO (Risk Reducing Bilateral Salpingo-opherectomy) significantly reduces the risk of ovarian and fallopian tube cancer in BRCA1 mutation carriers. The residual risk of primary peritoneal cancer after RRBSO is approximately 2%.

Management of Early Menopause
If riskreducing bilateral salpingooophorectomy (RRBSO) is undertaken prior to menopause, Hormone Replacement Therapy (HRT) should be considered to minimise potential cardiovascular complications and bone loss associated with premature menopause, until the time of natural menopause (approx. age 50 yrs). This use of HRT is safe and does not abrogate the protective effect of RRSO on breast cancer risk in BRCA1/2 mutation carriers and it may even be associated with a decreased risk.

The use of combination HRT beyond age 50 yrs should only be considered after specialist advice.

Contraception and Fertility
Combination oral contraceptive pill (OCP) is not contraindicated. A recent metaanalysis showed that the use of OCP is not significantly associated with breast cancer in BRCA1/2 mutation carriers.

Referrals