How genetic testing is guiding the use of PARP inhibitors

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Published: 8 May 2019
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Suzanne Mahon - Saint Louis University, Missouri, USA

Suzanne Mahon speaks to ecancer at ONS 2019 about how genetic testing is guiding the use of PARP inhibitors in treating patients with breast or ovarian cancer. 

She discusses whether PARP inhibitors could potentially be used to treat patients with inherited mutations other than BRCA, such as ATM or PALB2.

Suzanne concludes with the reminder that genetic testing - while very useful for determining the best treatment - may have other consequences for the individuals being tested and their families.

This programme has been supported by an unrestricted educational grant from Pfizer. 

If PARP is working too hard is a good way to think about it and we can identify it and we know that patients that have a BRCA1 or BRCA2 mutation that that’s part of that pathway then we can give the PARP inhibitor to turn it off, so to speak, is a good way to think about it.

How is genetic testing guiding the use of PARP inhibitors?

We know there are some tumours in breast and ovarian cancer especially that are impacted by PARP. So if that tumour has a mutation in the BRCA1 or the BRCA2 that that would guide or tailor or make for a personalised treatment with a PARP inhibitor agent. It is really changing what we do in the genetic world because we used to not think about offering genetic testing to someone if, say, they were 65 years old with metastatic breast cancer. That might not have been a reason to necessarily offer germline genetic testing because that really wouldn’t look like enough history but it would guide and change their treatment. So we are now seeing some families, individuals who do genetic testing and they find out that they do carry a BRCA1 or BRCA2 and that opens up this whole new set of challenges in that now their first degree relatives would be at risk, so their daughters and sons could be at risk or their siblings could be at risk. So this test that we pick that’s going to guide treatment has this very far-reaching effect for these families.

Do you think there is potential for using PARP inhibitors to treat patients with other inherited mutations such as ATM or PALB2?

We know that there are a number of genetic mutations that probably we need to pay more attention to and that they probably are affected by PARP because the PALB2 and the ATM, they are up- and downregulators of the BRCA1 and BRCA2. We don’t understand those genes as well. We don’t understand them as well from a hereditary point of view either. We know the risk for these other cancers may be associated with this but we don’t fully understand that. We also don’t fully understand how common some of those are. Testing for the ATM, PALB2, some of those genes, has been available probably routinely for about 3.5 to 4 years, so it’s not like the BRCA1 and BRCA2 where we’ve been testing since the early 2000s. We know a lot more about the risk associated with carrying those genes and we have a better idea of how common they really are in the general population. Until we do more testing overall we are not going to know how common these are but they are definitely part of the pathway. So when we do genetic testing we’re not usually just testing for just the BRCA1 and the BRCA2 but we’re testing for multiple things.

What do oncology nurses need to know with regards to the relationship between genetic testing and choosing treatments such as PARP inhibitors?

With our patients one of the things that oncology nurses need to be especially aware of, and physicians and everyone that orders it, is the concept that we order this and we’re thinking about the patient’s treatment in the moment that we do it. Patients need a little counselling even at that point that says that if we find something this is not going to be just about you anymore, that this is going to be about many of your other family members. It is devastating for individuals to learn that they have a genetic risk for developing cancer and a lot of times when this is presented they’re like, ‘Well, we’ll do this testing because it’s going to help us to pick a therapy,’ and that is absolutely correct but they don’t understand, patients and families don’t always understand, that they could also be learning something that they maybe weren’t prepared for. So anticipatory guidance as we manage these families and realising that it is devastating when they learn that and that if that’s been ordered and then we understand that the patient has it, that getting the rest of the family to the care they need is critical.