Hereditary Breast and Ovarian Cancer

BRCA and Preventive Surgery

From epidemiological research it is apparent that some families have high rates (or clusters) of members with either breast or ovarian cancer, or sometimes both.  This has become known as Hereditary Breast-Ovarian Cancer (HBOC).  With advances in molecular genetics, we have come to recognise abnormalities or mutations in the DNA of certain genes associated with HBOC.  The two most common are mutations are in genes called BRCA1 (located on chromosome 17) and BRCA2 (located on chromosome 13).  The actress Angelina Jolie bravely publicised the fact that she carries a BRCA1 mutation and has had preventive surgery as a result.  There are other lesser known and rarer genes such as BRIP1 and RAD51C which are also associated with HBOC.  With time and further advances in molecular genetics, it is likely that we will have a more complete picture or library of genetic mutations associated with HBOC.

BRCA1 gene mutations are associated with up to an 87% lifetime risk of breast cancer and an 63% lifetime risk of ovarian cancer.  The risk of these diseases typically escalates from the age of 40.  BRCA2 gene mutations are associated with up to an 84% lifetime risk of breast cancer and up to a 27% lifetime risk of ovarian cancer.  Typically, the risk of these diseases escalates from the age of 50.  There is a risk of other cancers as listed below from a review by Petrucelli.

Cancer Type

General Population Risk

Risk for Malignancy1 











Male breast



Up to 8.9%


6% through age 69

8.6% by age 65

15% by age 65
20% lifetime






1.       BRCA1 and BRCA2 Associated Hereditary Breast and Ovarian Cancer.  Petrucelli Nm, Daly MB and Pal T Gene Reviews 2016

The diagnosis of a BRCA gene mutation has traditionally been initiated by establishing a family tree or pedigree.  This can be inaccurate or misleading in up to 50% of true HBOC families sometimes reflecting small family size, adoption or other issues.  Formal genetic testing has traditionally been recommended when there is a greater than 10% risk of carrying a BRCA1 or 2 mutation.  This involves consultation with a clinical geneticist and either a blood or saliva test.  It is available through Genetic Health Queensland for no cost (strict eligibility criteria apply) or privately for about $400.  As costs come down, it is likely that more people, with lower risk estimates, will avail themselves of this test.

The advantages of genetic testing include:

  1. The opportunity for more intense screening of breast cancer +/- preventive surgery.
  2. The opportunity for preventive surgery for ovarian cancer.
  3. Valuable information for other family members.
  4. Tailored treatment of patients with established disease. Cancers that demonstrate the BRCA mutation respond well to newer treatments including the so-called PARP inhibitors.  About 15% of ovarian cancers are associated with an inherited BRCA mutation and another 10% will have a mutation just in the malignant ovarian tissue.

Unfortunately, there is no effective screening test for ovarian cancer, even in high risk populations like HBOC.  The oral contraceptive pill may mitigate the risk somewhat in reproductive aged women.  On a more positive note, there is very good evidence that preventive surgery significantly improves survival in at-risk groups.  Preventive surgery usually involves either removal of fallopian tubes and ovaries (BSO) or more typically removal of uterus, tubes and ovaries (THBSO).  These operations are nearly always performed via a laparoscopic (keyhole) approach and should be performed by an experienced laparoscopic surgeon with an interest in HBOC.

The timing of preventive surgery depends upon completion of family, and it is usually recommended that such surgery is undertaken at least 5(-10) years before the age at which other family members may have been diagnosed with disease.  For BRCA2 mutation carriers, surgery from age 45 is often recommended, and earlier for BRCA1 mutation carriers.  Risk reducing surgery is certainly recommended for post-menopausal women.

Sometimes there are well-meaning recommendations in the lay press about being “vigilant” for symptoms of early ovarian cancer.  Sadly, by the time people have symptoms, 75% will be diagnosed with advanced disease (stage 3 and 4).  This illustrates why preventive surgery is of value – there is no effective screening test and the disease most typically is quite advanced by the time there are symptoms.  While survival from ovarian cancer has increased over the last 2 decades, there is no doubt that “prevention is better than cure”. 

When the tubes and ovaries (+/- the uterus) are removed in reproductive age women, this will cause menopause.  There are several options for managing this depending on the type and extent of surgery.  These are important issues to consider and discuss when contemplating risk reducing surgery.