Research by Professor Diana Eccles and colleagues at the University of Southampton finds that many women with triple negative breast cancer should be offered BRCA gene testing.

Friday 5 December 2014      Latest research
Research finds many women with triple negative breast cancer should qualify for BRCA gene testing

What is triple negative breast cancer?

Around 15 per cent of breast cancers are found to be ‘triple negative’. This means they lack the three molecules which are normally used to classify breast cancers; the oestrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2).

This form of breast cancer cannot be treated with targeted drugs commonly used to treat other types of breast cancer, such as tamoxifen and aromatase inhibitors for ER and PR-positive breast cancer, or Herceptin for HER2-positive breast cancer. This leaves triple negative breast cancer patients with fewer treatment options, namely chemotherapy drugs in addition to surgery and/or radiotherapy.

The genetics behind triple negative – new evidence

From previous research we know that mutations in the BRCA1 gene are common in people who develop triple negative breast cancer. But the bigger picture of what kinds of gene mutations might be driving the progression of triple negative breast cancer, in people with or without a family history of the disease, hasn’t been fully investigated.

To learn more about the genetics of triple negative breast cancer, Professor Diana Eccles, at the University of Southampton and colleagues from across the world tested DNA samples donated by 1824 women with triple negative breast cancer for mutations in 17 genes that are linked to breast cancer, in work part-funded by Breast Cancer Campaign. This is the largest investigation to date of breast cancer gene mutations in triple negative breast cancer.

The results, published this week in the Journal of Clinical Oncology, showed that 14.5% (167) of the triple negative patients had inherited genetic mutations. The mutations were in 14 of the 17 genes being studied, the most common mutations being in the BRCA1 (155 mutations found) and BRCA2 (49 mutations found) genes. And women with a genetic mutation were more likely to be diagnosed at a younger age, with the average age at diagnosis being 45 years old, compared to 52 years for those with no mutations.

Many of the women with a genetic mutation also had no family history of breast or ovarian cancer, particularly those with a mutation in a gene other than the BRCA genes.

Why it matters for patients

As well as being important for preventing, or catching cancer earlier in people with a family history of breast cancer, testing for genetic mutations is becoming increasingly important in helping to shape treatment plans for people who already have breast cancer.

In the first instance this is because people with a genetic mutation may also opt for more drastic surgery to reduce the risk of developing breast cancer a second time around, for example having a double mastectomy instead of a lumpectomy. In addition, drugs including PARP inhibitors that target cancers with BRCA mutations, and other genetic faults, are currently in clinical trials – and so knowing how many people with triple negative disease are likely to have a genetic mutation could change whether they are automatically offered genetic testing, and ultimately change their treatment plan if they do have a mutation.

Should more people with triple negative breast cancer have genetic testing?

The current National Institute of Clinical Excellence (NICE) guideline for treatment of people with a family history of breast or ovarian cancer on the NHS recommends that if someone has a 10% or more likelihood of having a BRCA mutation then they can be offered genetic testing. Normally, this likelihood is calculated based on a person’s family history of breast and other cancers.

Although the findings from Professor Diana Eccles’ study agree with this recommendation they also highlight that given the number of people who were found to have inherited mutations in their study, most women aged under 40 with triple negative breast cancer do have a 10% likelihood of having a BRCA mutation, irrespective of their family history. The researchers add to this by saying that people diagnosed with triple negative breast cancer up to age 50 with no family history of the disease have just under a 10% likelihood (8.6%) of having a BRCA mutation, meaning they should also be offered genetic testing. In fact, limiting testing to women aged under 40 in their study would have missed 24% of people with mutations. 

In comparison with the UK guidelines, US guidelines from the National Comprehensive Cancer Network would only miss 1% of people with mutations – these guidelines recommend screening when there is a family history of cancer or a diagnosis of triple negative breast cancer under age 60.

Finally, if the costs of genetic testing keep falling, the researchers suggest that genetic testing for all people with triple negative breast cancer, irrespective of age and family history, could be considered.

Call to action

In our Help us find the cures action plan to overcome breast cancer, we encouraged NICE to regularly review research relating to their Familial Breast Cancer guideline to ensure emerging findings are quickly translated into patient benefit. The paper published this week is a clear example of the kind of new evidence that the guidelines could incorporate to help more women to overcome breast cancer by knowing about the genetic mutations driving their cancer.

Katherine Woods, Senior Research Communications Manager at Breast Cancer Campaign, said:

“Deciding whether to undergo genetic testing at diagnosis can cause additional anxiety for women at a very difficult time, so we also need to find the best ways to help them by providing the information and support they need to make informed decisions about genetic testing.”

“This is why Breast Cancer Campaign is now funding further research to create a decision aid to provide young women with information about the risks and benefits of genetic testing, enabling them to judge the different outcomes on what matters most to them.”