Familial Breast Cancer and Genetic Testing

As pointed out in our previous blog on Breast Cancer Risk Factors, 90% of breast cancers are sporadic, i.e., happen by chance. Genetics accounts for 5-10% of breast cancers in general. However, 25% of breast cancers in women < 30 years of age is due to an inherited pathogenic gene. If you have one or more close relatives that has been diagnosed with breast or ovarian cancer, you probably want to know if that indeed does increase your risk of breast cancer in future and if you need to do something about it. This blog is written to demystify the rather complex topic of familial breast cancer and prepare you for a more individualised discussion with your specialist. 

How is the risk of familial breast cancer assessed?

Based on the number of affected relatives with breast or ovarian cancer, women are divided into three categories, Table 1. The best way to work out which category you belong in is to use the iPrevent tool from Peter MacCallum Cancer Centre. This tool not only considers your family history but also includes lifestyle, reproductive, and histological risk factors.

Table 1. Australian NHMRC National Breast & Ovarian Cancer Centre risk classification for familial breast cancer.

What are the screening recommendation for women in each category?

Table 2 summarises the breast screening regimen recommended for women based on their risk category. For women at moderate or high risk, referral to a familial breast cancer clinic or a breast surgeon is recommended. Importantly the radiological screening does not replace self-monthly breast checks. No one knows the texture and feel of your breast better than yourself. Doing regular monthly self-breast examinations helps you to pick up new sings at an earlier stage. 

Table 2. Breast screening recommendations based on the risk category.

What about genetic testing?

For a woman with a personal diagnosis of breast cancer the indications for genetic testing is listed in Table 3. 

Table 3. Indications for genetic testing in patients with personal history of breast cancers.

For women without personal history of breast cancer the decision to proceed with genetic testing is more complex and it is important that its implications are well understood before undergoing the test. For this reason, referral to a familial breast cancer clinic or a breast surgeon is recommended for women at moderate or high risk of familial breast cancer. 

If a pathogenic mutation such as BRCA1/2 is identified through the genetic testing, the subsequent recommendation will be based on the gene identified. However, if no pathogenic mutation identified, the result of the test should be interpreted in the light of genetic test result of her affected family member(s). Therefore, a negative result could be either: 

1. Informative: when a pathogenic mutation is identified in the affected family member. This is excellent news for the woman, as she will be back to the average population risk for breast cancer. 

2. Non-informative: when the affected family has either not been tested or has returned a negative genetic test result. In this case a negative result does not mean that the woman is no longer at increased familial risk of breast cancer and should continue to be managed based on her original risk category. That’s why in women without a personal history of breast cancer but multiple family members with breast or ovarian cancer, we always recommended genetic testing to be done in the affected family members first. 

In addition, the result of genetic testing can have implications on life, critical illness, income protections, and health insurance. These implications often expand to the relatives and family members who are required to disclose this information. These issues should be considered when planning to undergo genetic testing. 

What risk-reducing strategies are available to women at high risk of familial breast cancer?

In addition to management of modifiable risk factors for breast cancer including keeping a healthy weight, no smoking, alcohol in moderation, minimise use of combined HRT, and regular physical activity, women at high risk of familial breast cancer may be offered three options: 

1. Intensive surveillance: Although this will not reduce the chance of breast cancer developing, but modern breast imaging is very effective in picking up breast cancers at a very early curable stage. In a study we published in 2020 no cancer was missed in 6,686 screening rounds performed over 8 years for Australian women at high risk of familial breast cancer!

2. Risk-reducing surgery: The most effective risk-reducing strategy is prophylactic bilateral mastectomy. This will reduce the chance of future breast cancer by 90-95%. Immediate breast reconstruction should be discussed if the woman decides to take this option. 

3. Tamoxifen: Tamoxifen is a selective oestrogen receptor modulator that is often used as adjuvant therapy following surgery in patients with hormone positive breast cancer (see our blog on Breast Cancer Subtypes). Some women at high familial risk of breast cancer may be offered tamoxifen as a risk-reducing strategy. It offers about 50% risk-reduction depending on the type of gene mutation; however, this moderate risk reduction comes at a cost of significant side effects that should be discussed before embarking on this decision.