Personalised risk-stratified breast cancer screening for BRCA germline mutations and other genes

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Published: 31 Jan 2023
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Prof Banu Arun - MD Anderson Cancer Center, Houston, USA

Prof Banu Arun speaks to ecancer at BGICC 2023 about personalised risk-stratified breast cancer screening for BRCA germline mutations and other genes.

She highlights the significant impact next generation gene sequencing has had on increasing genetic testing for germline mutations that relate to breast cancer.

Prof Arun outlines the importance of taking personal and family history of cancer into account, during discussions with patients, when considering a preventive mastectomy for hereditary breast cancer genes that are not BRCA1 or BRCA2.

My second talk relates to personal risk, personalised risk screening, for patients with BRCA germline mutations but also other hereditary breast cancer genes. As we all know, with the advent of having next generation gene sequencing available, genetic testing for germline mutations that relate to breast cancer has increased significantly. Now we have panels available that test for multiple genes beyond BRCA1 and 2, that includes PALB2, ATM, CHEK2, CDH1 and p53 amongst others. Obviously, because now we test for these genes we also receive positive test results. The question is what do we do with these results. 

The way we can approach it is, that I do in my practice is, have an algorithm that relates to patients who already have a diagnosis with breast cancer and to individuals who don’t have cancer but screening is indicated. For patients with a personal history of breast cancer, the implications of finding a germline mutation is important. Most of the data we have is related to BRCA1 and 2 because that’s one of the oldest genes and we have long-term follow-up; the other genes are newer so we don’t have a lot of information, prospective information, on risk interventions. For the audience who is interested, there are detailed guidelines in the NCCN, actually the new version 2 of 2023 came out last week.

For BRCA germline mutation carriers who have breast cancer, screening options for breast include, if they do not undergo preventive mastectomy, would be to continue mammographic screening with breast MRIs that can be done together annually or you can alternate every six months in a staggered way. For other mutation carriers, such as PALB2, p53, ATM mutations, again we would recommend to continue with mammographic screening and consider adding breast MRIs at age 30 or after 40, depending on the gene. Again, the details of that is in my talk as well as the NCCN guidelines. That’s for affected individuals. 

For unaffected individuals breast cancer screening is similar. For BRCA1 and 2 we start breast MRI screening at age 25 and add mammograms at age 30 and do it yearly thereafter until age 75 when it becomes a discussion of pros and cons of continuing with the imaging. But I can tell you I think an otherwise healthy woman at age 75, many of my patients don’t want to stop but some may want to stop and say, ‘This is enough screening for me.’ There are other age cut-offs or starting ages for mammograms and MRIs for other genes that are detailed in my talk and NCCN. But it’s important that these are discussed with the patients up front so that they know that it’s a commitment.

The more difficult discussion for genes beyond BRCA1 and 2 is the data and the benefit of doing bilateral preventive mastectomies. We have data for BRCA1 and 2 that show that breast cancer risk can be decreased by more than 95% when preventive mastectomies are done but we really don’t have long-term follow-up prospective data for the other genes. Therefore, I think it’s a discussion, it’s not a strong recommendation but a personal, as well as family, history of cancer needs to be taken into account when the patient discusses preventive mastectomies for hereditary breast cancer genes that are not BRCA1 or BRCA2.