Genetic Testing for BRCA Mutations is Vital in Breast Cancer Treatment


Patients with a higher likelihood to develop BRCA 1 or BRCA 2 mutations are slipping through the cracks, making testing for these mutations a vital part of any breast cancer treatment plan.

It’s important for their providers to test for BRCA1 and BRCA2 gene mutations in patients with breast cancer as those with the highest likelihood of developing this mutation are being missed by clinicians, according to Susan M. Domchek, MD, director of the MacDonald Women’s Cancer Risk Evaluation Center at the University of Pennsylvania.

At the 21st Annual Lynn Sage Breast Cancer Symposium, Domchek spoke with OncLive® a sister publication of Oncology Nursing News®, about the importance of genetic testing and making sure patients with the highest risk of developing these mutations are caught early on in their treatment.

OncLive®: What are low to moderate penetrance genes? And how they can affect patients with breast cancer?

Domchek: In the past, we focused on genetic testing for inherited susceptibility to breast cancer in BRCA1 and BRCA2. If you have a mutation in one of these genes, you have a very high risk of developing breast cancer and ovarian cancer and other cancers. But what's happened in the last 5-10 years is that we can now test quickly and efficiently for many different genes and bonds. What this has meant is that we can now send genetic testing for 5, 10, 25, 80 genes all at the same time. What we need to do now is really understand what it means to have a mutation in other genes and what to do about them. Many of these genes are what we call moderate penetrance genes. And that just means that the relative risk of cancer is more in the 2-4 range, rather than the much higher range associated with BRCA1 and BRCA2 mutations.

What role does genetic testing have in the treatment of breast cancer?

There is a lot of debate and controversy right now about what the threshold should be for genetic testing individuals with breast cancer. There are NCCN guidelines, which talk about this and are focused on things like age and family history, and the type of breast cancer. With triple-negative breast cancer, for instance, being much more likely to have a mutation in a high penetrance gene. We're stating that the NCCN guidelines were created to identify individuals at risk of having these high penetrance gene mutations, they weren't really developed to detect mutations and other genes, such as CHEK2 or ATM, where the information related to that is just less clear how much we are adding clinical utility to patient care.

There are other guidelines, including the American Society of Breast Surgeons, which have now suggested that everybody get genetic testing when they have a new diagnosis of cancer. And the challenge there is just how we think about that, and I would argue that it remains true that BRCA1 and BRCA2, and for instance probably 2, are the genes that are most clinically useful of this time in terms of improving patient care, and that it is clear that some women, and all men, are at a much higher risk of having these mutations than others. And so, we should make sure not to miss anybody in that category.

How can these mutations affect treatment options?

BRCA1 and BRCA2 mutations have a clear role in consideration of surgical approaches. For example, if one has a BRCA1 or BRCA2 mutation, and depending on their age, we can estimate the risk of developing a second primary cancer and someone will choose to have a bilateral mastectomy rather than, for instance, a lumpectomy and radiation. Because of the increased risk of ovarian cancer with BRCA1 and BRCA2 mutations, women at some point will require a preventative oophorectomy. Finally, especially right now, for an advanced breast cancer patient, there are specific drugs, PARP inhibitors, olaparib (Lynparza) and talazoparib (Talzenna), which are approved to treat metastatic BRCA1/2-related breast cancer.

Currently, there's no approval for early-stage breast cancer patients for PARP inhibitors and if that approval comes, we'll have to reassess things. For mutations in these other genes, that direct impact is less clear at this time. There are no known therapeutic differences, meaning we don't give specific drugs to individuals who have mutations and CHEK2 or ATM mutations at this time. And a lot of the guidelines focus on enhanced breast screening with breast MRI, which is probably more relevant for someone who hasn't yet had their breast cancer. So we have to figure out how to best use this information.

What should clinicians and nurses take away from this information?

We currently miss people at the highest risk for having BRCA1 and BRCA2 mutations, and then there are socioeconomic disparities and racial disparities. We need to really make sure that we're testing those who are at the highest risk. Secondly, if you choose to send the multi-team panel test, just make sure you know what genes are on the panel and make sure you understand what we might do with that information. I think it's really important that we know kind of what we're getting into before we do it and that our patients understand the pros and cons of expanded panel testing.

How would you make sure clinicians and nurses don’t miss patients at the highest risk for BRCA mutations?

I think that in the past, there had been a number of barriers to genetic testing. We might have made it too hard for individuals to access such testing, the costs were at least perceived as being too high. We need to make sure that patients know that if they meet criteria for testing, the vast majority of the time insurance covers the cost of the test, and also there are low-cost options available. But we also need to meet patients where they are, meaning, we need to make sure that it's easy for patients to get access to genetic testing information.

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