Tag Archive for: BRCA genes

How Do Genetic Mutations Impact Breast Cancer Risk, Prognosis and Treatment?

How Do Genetic Mutations Impact Breast Cancer Risk, Prognosis and Treatment? from Patient Empowerment Network on Vimeo.

For breast cancer patients, how do genetic mutations impact risk, prognosis, and treatment? Expert Dr. Sarah Sammons provides insight about currently known genetic mutations and their impact on breast cancer care.

Dr. Sarah Sammons is an oncologist at Duke Cancer Institute and Assistant Professor of Medicine at Duke University School of Medicine. Learn more about Dr. Sammons here.

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What are the known genetic mutations that can increase breast cancer risk?

Dr. Sammons:

Very good question. So, about 5 to 10 percent of all breast cancers are related to inherited genes. The most common ones that most patients have heard of, or most people have heard of in the media, are the BRCA1 and BRCA2, the BRCA genes. Those genes make patients highly susceptible to developing breast cancer throughout their lifetime. We’re talking 60 to 80 percent risk.

There are, over time, other genes that we have found also predispose patients to developing breast cancer.

There are over 10 at this point. Some of the most common ones are CHEK2, PALB2, PTEN, TP53, and CDH1. There are a few others, but those are kind of the main ones.

So, really when you develop a diagnosis of breast cancer, your oncologist and/or your surgeon will take a family history. They’ll keep into account your age, the type of breast cancer that you have, and we really have specific criteria now in which patients would qualify for genetic testing.

Genetic testing not only has become important to understand if you have a gene that could predispose you or your family to breast cancer, but we now have drugs that specifically target or are biomarkers for BRCA1 and BRCA2.

So, now it’s going to become even more important to test patients with early state and metastatic breast cancer because we have drugs that could actually specifically target BRCA.


How do these mutations impact a metastatic breast cancer patient’s treatment path?

Dr. Sammons:

Sure. Well, we can start with germline. So, really, right now, the only germline mutations that really impact a patient’s treatment are the BRCA1 and the BRCA2 genes. So, for patients that have germline mutations in BRCA1, we have a class of drugs called PARP inhibitors, that have been

shown to be more effective than chemotherapy in those patients. So, really, any patient that has a HER2-negative breast cancer – these genes are approved in HER2-negative breast cancer, so triple-negative or hormone receptor-positive breast cancer in patients that have a BRCA mutation.

It’s pretty critical to have this germline testing done because if they do have a mutation, then we would have a therapy for them that was more effective than chemotherapy. So, that’s why it’s important in that setting.

We’re also learning more and more, and research is evolving, that probably patients that have germline PALB2 mutations also may benefit from PARP inhibitors, but that data is still evolving.

In terms of somatic gene mutations, or next generation sequencing, your doctor might say that, “I want to send your tumor to look at the genes in the tumor that will help me decide what could be the next best therapy for you.” So, we would get a biopsy or use an old biopsy, and send your tumor to a variety of different companies that do this type of sequencing.

Some of them include FoundationOne, Curis, Tempus. And it would come back with a panel that would show what genes were mutated in your breast cancer.

About 40 percent of patients with hormone receptor-positive breast cancer have something called a PIK3CA mutation. And we have a drug called alpelisib (Piqray) that specifically targets that mutation.

Germline mutations usually also show up in the somatic testing. So, a BRCA mutation may also show up. The next generation sequencing also tests something called tumor molecular burden, which tells us basically how many mutations are altered in the DNA of your cancer. And we know that if you have many mutations, that you might be more likely to benefit from immunotherapy.

So, that’s another thing that we look at when we send that genomic sequencing. So, there are a variety of mutations and biomarkers that we can learn from sequencing the breast cancer, that will help us decide what’s the next best treatment for you in your metastatic breast cancer course.


What about prognosis, Dr. Sammons? Do these genes impact how a patient’s cancer may behave?

Dr. Sammons:

That’s a good question. The short answer is: Research is still evolving in this area, but I would say yes.


It sounds like it’s a qualified yet.

Dr. Sammons:

It’s a qualified yes. So, I would say for germline BRCA1 – we know that patients with germline BRCA1 are more likely to have triple-negative breast cancer.

So, in terms of early-stage disease, we know that triple negative breast cancer has a worse prognosis, a higher risk of coming back. But the FDA actually just approved PARP inhibitors in the early-stage setting for patients with BRCA mutations because it reduced the risk of recurrence.

So, where that settles out: Yes, we know that BRCA1 carriers are more likely to have triple-negative. Triple-negative is more likely to relapse, but every year we have newer and newer therapies that reduce the risk of relapse.

In the metastatic setting, BRCA carriers sometimes actually have been shown to live longer than patients without BRCA mutations because they’re more likely to respond to chemotherapy. We have the PARP inhibitor option – for all of those reasons.

In terms of gene mutations in the tumor, we do know that patients that have something called ESR1 mutations – so, if you have a hormone receptor-positive breast cancer, you have something called an ESR1 mutation.

We know that that means that you would be resistant to many of our endocrine therapies. And patients that have ESR1 mutations do usually have a shorter prognosis than patients that don’t.

So, there are a variety of mutations that are appearing to have impact on prognosis. 

Prostate Cancer Treatment Decisions: How Do Genetic Test Results Impact Your Options?

Prostate Cancer Treatment Decisions: How Do Genetic Test Results Impact Your Options? from Patient Empowerment Network on Vimeo.

How do genetic test results impact prostate cancer treatment options? Dr. Nima Sharifi explains BRCA mutations, germline genes, and somatic mutations—and discusses when treatment with PARP inhibitors may be appropriate.

Dr. Nima Sharifi is Director of the Genitourinary (GU) Malignancies Research Center at the Cleveland Clinic. Learn more here.

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Dr. Sharifi:        

There are several types of mutations that occur in prostate cancer. We know about a lot of them. We’re beginning to understand the function of many of them, and the role of just a few of them has become a bit clearer in treatment of prostate cancer. So, the one that I think has the clearest implications is something called BRCA mutations.

So, you can get mutations in genes that regulate DNA damage. This can occur in either inherited genes, or these are mutations that can occur in the cancer itself. And this will allow for tumors to become the developed – actually, greater DNA damage. The implications of using this information, genetic testing for these BRCA mutations, are actually several. One is that it may – if it comes in through the germline, then it tells us something about the hereditary or familial component of it.

So, that has implications not only for the patient but also potentially family members. And then the second set of implications has to do with treatment, and specifically treatment that in more advanced cases where there are now two FDA-approved agents that are used specifically for patients who have mutations in these genes.

And we’re still learning a lot about what these genes mean, or mutations of these genes mean for patients in their clinical course. And we’re learning much more information about other mutations which may occur in prostate cancer as well.

So, we should draw a distinction between two different types of genes. One is germline. Germline has to do with the DNA or the genes that you inherit from your parents. And the second category is somatic mutations, or somatic genetics. And this, specifically, has to do with mutations that occur in the cancer cell itself, but that are not inherited from one’s parents.

It’s a very active area of research. So, again, for the vast majority of mutations that we recognize in prostate cancer, we don’t use that to make clinical decisions. There are a few, such as the DNA damage repair genes or BRCA genes – which tell us something about the potential for a more aggressive disease course or a more aggressive disease – and also the potential appropriateness of using agents called PARP inhibitors, which seem to specifically work in patients who have mutations in the BRCA family of genes.

So, in terms of the treatment options, the major genetic tests that allow us to figure out whether systemic or drug treatment option is appropriate or not, is in DNA damage repair genes such as BRCA.

So, for example, in the case of metastatic disease that’s resistant to hormonal therapy and has already been treated with other therapies, if there is a mutation in BRCA or one of the closely related gene members, then use of a drug called a PARP inhibitor may be appropriate, and that could benefit patients.