Tag Archive for: BRCA mutation

How Is Ovarian Cancer Detected?

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Dr. Nita Karnik Lee discusses how ovarian cancer is diagnosed, shares challenges in screening tests and procedures, and reviews ongoing research in the field. Dr. Lee also shares key questions to ask one’s healthcare team about ovarian cancer detection.

Dr. Nita Karnik Lee is a Gynecologic Oncologist at The University of Chicago Medicine. Learn more about Dr. Lee.

See More from DETECT Ovarian Cancer

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How Does Biomarker Testing Impact Ovarian Cancer Screening and Detection?

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What Are the Symptoms of Ovarian Cancer?

 Patient Empowerment | Advice From an Ovarian Cancer Expert

Patient Empowerment | Advice From an Ovarian Cancer Expert

Transcript:

Katherine Banwell:  

Dr. Lee, what are the screening tests and procedures to detect ovarian cancer? 

Dr. Nita Karnik Lee:  

So, one of the important things to realize is that we do not actually have a screening test for ovarian cancer. That’s really important for the general public who maybe is at average risk. Patients who have a strong family history or a genetic, hereditary condition, sometimes we do use ultrasound and CA125, but that’s not considered a screening test for average-risk patients. We’re very limited in that sense for ovarian cancer. There’s a lot of research that’s being done about this.  

Katherine Banwell:  

Have there been advances in screening or screening technology that patients should know about? 

Dr. Nita Karnik Lee:  

I think the issue with screening and ovarian cancer is because we have not had any, and there have been really large studies that have been done both in the U.S. and in Europe, trying to see does ultrasound work every six months. Does CA125 and ultrasound work?

There’s some combination of blood tests that have started to become a little bit more researched in terms of going further along, but there’s really nothing that’s the perfect answer. One of the really important things that we talk about is knowing family history to see if there’s something that can be done to help patients who have a family history.  

And then also being really aware of subtle symptoms of ovarian cancer that can trigger you going to your doctor and then really pushing and advocating for yourself and your family member to get a workup done, which can often include an exam, an ultrasound, and maybe even something like a CAT scan or CT scan if any of the symptoms are a little more worrisome.  

Katherine Banwell:  

What questions should patients ask their doctor about detection? 

Dr. Nita Karnik Lee:  

I think that when we’re thinking about detection, or if somebody has these symptoms coming up, definitely asking, like, hey, you know what? I’m seeing you as an internist, but I haven’t had a pelvic exam. So, making sure you’re seeing a gynecologist or an internist or family medicine doctor who can do a vaginal and a rectal exam is one important step. Perhaps getting an ultrasound or perhaps getting a CAT scan if the symptoms are more significant.  

Unfortunately, we still see a lot of women who have these sort of vague symptoms, maybe they’re GI-related, and they get a workup for like six months on an EGD, or a colonoscopy, or they tried Pepcid. And all of those things are good, and they’re not unreasonable to do, but I think something else that can be done in addition would be a pelvic ultrasound, as an example.

I would say that if somebody doesn’t have any of those symptoms, but they have a family history, that’s why we’re in a little bit more of a bind as to know what the right thing to do is. We know that for patients who have a known BRCA mutation and are not ready for risk reduction surgery, we often will use ultrasound, but we know that ultrasound is not perfect. 

Essential Genetic Testing for Personalized Gynecologic Cancer Treatment

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How important is genetic testing for gynecologic cancer? Expert Dr. Ramez Eskander from UC San Diego Health discusses the role of genetic testing in gynecologic cancer care – including molecular tumor testing, germline testing, HRD tests, and BRCA mutations – along with proactive patient advice. 

[ACT]IVATION TIP

“…every patient with ovarian cancer needs to know their BRCA status and needs to know their molecular tumor testing status. Feel empowered to ask these questions. It is data that you should have at hand as you make informed decisions.”

See More from [ACT]IVATED Ovarian Cancer

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Optimizing Ovarian Cancer Care: Genetic Testing and Treatment Approaches

Optimizing Ovarian Cancer Care: Genetic Testing and Treatment Approaches

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PARP Inhibitors in Ovarian Cancer Treatment: Understanding Side Effects

 What Are Common Symptoms of Ovarian Cancer

What Are Common Symptoms of Ovarian Cancer?

Transcript:

Lisa Hatfield:

Dr. Eskander, for patients newly diagnosed with a gynecologic cancer, how important is it to get genetic testing like HRD or homologous recombination deficiency, and how can understanding one’s genetic profile help them and their care team choose the best treatment?

Dr. Ramez Eskander:

This is an incredibly important question. It is pivotal that every newly diagnosed ovarian cancer patient have germline genetic testing and molecular tumor testing because of the impact it can have on their treatment strategy, independent of course, the importance of them being diagnosed. So that if they had a genetically inherited mutation, we call it germline mutation, their relatives can be informed and tested, so they can have risk reducing surgical interventions.

In the ovarian cancer setting, homologous recombination deficiency testing is crucial, because it helps inform the magnitude of benefit that we might see with treatment strategy, in this case, combination of PARP inhibitor plus bevacizumab (Avastin) or PARP inhibitor alone. So these treatment strategies have been proven to improve clinical outcomes. And knowing HRD test status and knowing whether you have a germline mutation is pivotal to putting context around a conversation surrounding maintenance treatment approaches. And understanding the profile is what drives your ability to make an informed decision about your maintenance treatment strategies.

And it can be quite nuanced. For example, if a patient is HRD test-negative, they would have to make a decision about what kind of maintenance therapy with their provider. Do I do maintenance treatment? Should I do bevacizumab alone? Should I do a PARP inhibitor alone? And what might I anticipate with either of these approaches, and what are the pros and the cons? And an HRD test-positive patient, there is clear data supporting the use of PARP inhibitors or PARP inhibitors plus bevacizumab in combination.

So you want to be informed of those data as you look to make a decision. And this to me is germane to the care of patients with ovarian cancer. Every patient should know their status and in a similar manner when we talk about endometrial cancer, I would just like to elaborate that it’s critical to know what is the finding of the testing on the tumor for the endometrial cancer? Is this a mismatch repair-deficient or mismatch repair-proficient endometrial cancer and testing that was done? 

Lisa Hatfield:

That’s a lot of information. So I just want to clarify a couple of comments that you made. So when you talk about the germline testing of germline mutations, that has to do with mutations that are present in a patient’s, all the cells in a patient’s body. Is that correct? So like the BRCA1 and 2 genes?

Dr. Ramez Eskander:

That’s correct.

Lisa Hatfield:

And then there are the other types of mutations, some people call them somatic mutations that are just have to do with the DNA sequencing of the actual tumor or cancer cells. So is HRD then, is that a germline mutation, or is that more of a somatic?

Dr. Ramez Eskander:

Perfect question. So HRD itself isn’t a mutation. HRD is looking at changes in the tumor DNA, but you bring up a perfect point. A germline mutation is inherited, meaning that it is in every cell, and it’s a predisposition and increase in cancer risk. Somatic mutations are not inherited. Somatic mutations are mutations in the tumor unique to that cancer. That’s why we talk about informing your family or relatives with a germline mutation, because that was inherited. And other people in the family may have the same inherited mutation. Somatic mutations are not inherited. They arise in the cancer, and they require tumor testing to inform.

Homologous recombination deficiency isn’t looking for a specific mutation, but it’s rather examining the tumor DNA to look for something we call genomic scarring. The analogy I gave is if I’m driving on the freeway and I’m stuck in traffic, I know that I’m stuck in traffic, but I don’t know exactly why. Is there construction on the freeway? Is there an accident? It’s unclear. So the HRD is looking at the genomic signature, and it needs tumor samples to do that, but it’s not honing in on a specific mutation.

I know it can get a little bit complicated. I’ll just add this, A patient who has a germline BRCA mutation, if you test their tumor, the near vast majority are going to have an HRD test-positive signature, because it drives that. So that’s like saying, I know the reason that there’s that genomic instability, it’s a BRCA mutation, but there are patients we call beyond BRCA. There are many things that may cause this independent of BRCA that we may not know of right now, but we can identify the genomic scar, and that qualifies patients as having a homologous recombination deficiency test-positive tumor. 

So my tip is every patient with ovarian cancer needs to know their BRCA status and needs to know their molecular tumor testing status. Feel empowered to ask these questions. It is data that you should have at hand as you make informed decisions.

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Optimizing Ovarian Cancer Care: Genetic Testing and Treatment Approaches

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What’s vital for ovarian cancer patients to know about treatment options and approaches? Expert Dr. Ramez Eskander from UC San Diego Health discusses chemotherapy, surgery, the importance of molecular testing, treatment approaches for optimal outcomes, and proactive patient advice. 

[ACT]IVATION TIP

“…ask the questions of your provider. Understand, did you have genetic testing? Did you have molecular tumor testing? And do the results of that genetic or molecular tumor testing impact the treatment recommendations for maintenance therapy? I want to make sure everybody feels empowered to ask those questions and have those answers.”

See More from [ACT]IVATED Ovarian Cancer

Related Resources:

PARP Inhibitors in Ovarian Cancer Treatment: Understanding Side Effects

PARP Inhibitors in Ovarian Cancer Treatment: Understanding Side Effects

 Essential Genetic Testing for Personalized Gynecologic Cancer Treatment

Essential Genetic Testing for Personalized Gynecologic Cancer Treatment

 What Should Ovarian Cancer Know About Immunotherapy and Targeted Therapies

What Should Ovarian Cancer Know About Immunotherapy and Targeted Therapies

Transcript:

Lisa Hatfield:

Dr. Eskander, for someone who is newly diagnosed with ovarian cancer, what are the most common treatment options available, and how can patients know which treatment plan is best suited for their specific situation?

Dr. Ramez Eskander:

Newly diagnosed ovarian cancer is managed utilizing chemotherapy and surgery. The order can vary depending on the specific patient, how they present, their cancer burden, whether you receive chemotherapy, surgery, followed by chemotherapy, or surgery and chemotherapy. The drugs, the backbone of treatment, are very similar, that is, two chemotherapy drugs called carboplatin (Paraplatin) and paclitaxel (Taxol). I will say that there are other drugs used in the front line. Another drug that’s commonly used is a drug called bevacizumab or Avastin. This is called an anti-angiogenic drug.

And we’ve also identified biomarkers that have really transformed front-line management. Any and every newly diagnosed ovarian cancer patient should have genetic testing because about 15 percent of ovarian cancers can have a genetic predisposition, meaning that you’ve inherited a gene that increased your risk of developing the cancer. And that’s critically important for the treatment of that patient, but also for any family members who would benefit from what we call cascade genetic testing, they would get tested. And if they were identified to have the gene, they could be followed and have risk-reducing surgery.

The reason this molecular testing of ovarian cancer and again, every patient should have genetic testing and molecular testing is critically important is it is informing maintenance treatment strategies. We’ve now conducted several clinical trials that show the utilization of a class of drug called PARP inhibitors. These are oral pills. When we use these medications in patients who have a BRCA mutation, there is a dramatic improvement in clinical outcome.

So every advanced stage ovarian cancer patient should be tested. And for those who have a BRCA mutation, every one of those patients should be treated with a maintenance PARP inhibitor. And maintenance meaning after you finish the chemotherapy drugs that I mentioned, you go on to that maintenance PARP inhibitor. And we’ve also had clinical trials that have expanded that opportunity, because not only are we looking at patients that have a BRCA mutation, but we’ve now expanded and incorporate into patients who are homologous recombination-deficient, or HRD test-positive.

Because studies have shown that when you give the PARP inhibitors in combination with bevacizumab, the drug that I alluded to a moment ago, you can again get a very significant improvement in clinical outcome including an improvement in overall survival. So biomarker testing, genetic testing, chemotherapy plus surgery is a backbone but importantly utilizing that molecular testing to inform maintenance treatment strategies which have clearly improved clinical outcomes, and these are all very critical conversations to have with the physician who’s taking care of you.

And for me, my [ACT]IVATION tip here is ask the questions of your provider. Understand, did you have genetic testing? Did you have molecular tumor testing? And do the results of that genetic or molecular tumor testing impact the treatment recommendations for maintenance therapy? I want to make sure everybody feels empowered to ask those questions and have those answers.

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Prostate Cancer | Advances in Research and Technology

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Prostate Cancer | Advances in Research and Technology from Patient Empowerment Network on Vimeo.

What are the latest prostate cancer research advancements? Expert Dr. Rana McKay discusses recent prostate cancer treatment approvals, ongoing research, and genetic testing developments.

Dr. Rana McKay is an associate clinical professor of medicine at Moores Cancer Center at UC San Diego Health. Learn more about Dr. McKay.

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Overcoming Barriers | Advice for Accessing Prostate Cancer Clinical Trials

Transcript:

Katherine:

Well, let’s dive into developing research and what it could mean for patients. Are there recent research highlights that you could share with the audience?  

Dr. McKay:

Absolutely. I think the newest approvals that have occurred in prostate cancer have been the approvals of combination PARP inhibitors, which block the ability of cancer cells to repair their DNA combined with hormonal agents such as abiraterone (Zytiga) or enzalutamide (Xtandi) for patients who have specific mutations in their tumor and their tumor is no longer responding to treatment. Those are the newest FDA approvals that were recently highlighted and shared.  

Katherine:

What areas of research do you specialize in? 

Dr. McKay:

The areas of research that I specialize in are particularly around novel therapeutics for patients with advanced prostate cancer, biomarker development precision medicine strategies for patients across the spectrum. And actually, also, in the localized setting, thinking about how we can attempt to cure more patients with prostate cancer by integrating our systemic therapy with surgical and radiation strategies to improve survival outcomes for patients and ultimately, cure it for patients by using effective systemic therapy early on so patients never recur.   

Katherine:

We’ve been hearing a lot recently about innovations in technology. How are these advances accelerating prostate cancer care?  

Dr. McKay:

Innovations of technology have absolutely been revolutionizing prostate cancer care I think from the diagnostic side, there’s new imaging modalities that are getting more refined. On the molecular side, there’s now different kinds of genetic tests. And our ability for us to do these tests, and do them quickly, and get results in real time that we can make decisions on we’ve come a long way from when we first sequenced the human genome. We’re now able to do that so quickly multiple times over in a very streamlined kind of way. And then, I have to say that there’s been tremendous improvement in our modalities of administrating therapies.  

So, our therapies are getting more novel, they’re getting more precise. What I mean, by that is targeted radioligand therapy, targeting linking a small molecule that binds PSMA, labeling it with a payload that is radiation therapy or kind of radio therapy/radio particle doing the same thing with chemotherapy, developing antibody drug conjugates. There’s androgen receptor degraders. There’s different ways of administrating immunotherapy by specific antibodies. So, there’s just the different sorts of treatments that are out there.  

We’ve just come such a long way from hormone therapy, which is still very important in chemotherapy to other different modes of action with the different systemic treatments we have.  

Katherine:

What about individual patients? Is there research into understanding a person’s – just one person’s disease?  

Dr. McKay:

Absolutely. I mean, that is in essence, precision medicine. I think we are now molecularly profiling tumors that is standard of care for anybody with advanced disease to undergo hereditary tumor profiling and – or hereditary profiling of just normal cells in the body, if there’s any sort of genetic abnormalities. But also, the tumor itself, and able to do that all for the actual biopsy specimen, or surgical specimen, and also blood. And then, based off of that individual’s genetic makeup, or the genetic makeup of the tumor, or the immune profile of the tumor actually trying to target therapy.  

There is a clinical trial that we are eagerly developing through the alliance, which we hope will open to enrollment before the end of the year, called the PREDICT Study. And this study is using that very notion of taking somebody’s DNA and RNA from their specific tumor, and based off of their results, strategizing the treatment around what kind of genetic makeup is in the tumor. And I think we’re moving towards that.  

Katherine:

What about common genetic mutations and what are you learning about people who have other genetic mutations like the BRCA mutation?  

Dr. McKay:

For patients who have BRCA mutations, first I’ll say, the prevalence of BRCA mutations varies across the stage of prostate cancer that somebody has. In the localized setting, the prevalence is a lot lower on the order of 2 to 4 percent depending on somebody’s risk profile. In the advanced setting, it is higher, 6 to 8 percent. Patients who have BRCA alterations are particularly susceptible to PARP inhibitors, which are oral drugs that can be given that when given in an individual who’s got a BRCA mutation, can cause cell death; can cause a tumor cell to die. And so, that’s a very good thing.  

I think the other thing, if thinking about the type of BRCA alterations, if there’s something that’s hereditary, this information is prognostic and predictive in that in can guide how people are going to – how we think they may do and what they may respond to. But it’s also really important because it can inform cascade testing for family members. It could also inform screening for secondary cancers in that individual who has prostate cancer with a known BRCA alteration. So, I think there’s a lot of personalization that happens based off of the molecular profiling results.  

Hereditary Ovarian Cancer: What’s Your Risk?

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Hereditary Ovarian Cancer: What’s Your Risk? from Patient Empowerment Network on Vimeo.

What should patients know about ovarian cancer and hereditary risk? Expert Dr. Ebony Hoskins explains the incidence rate of hereditary ovarian cancer and shares advice about when it’s important to ensure you get genetic testing.

Dr. Hoskins is a board-certified gynecologic oncologist at MedStar Washington Hospital Center and assistant professor of Clinical Obstetrics and Gynecology at Georgetown University Medical Center. Hoskins sees women for gynecological malignancies, which include the treatment of endometrial, ovarian, vulva, vaginal and cervical cancers.

[ACT]IVATION TIP

“…if you know someone who has ovarian cancer or if you’re affected yourself, make sure you have gotten genetics testing standard of care.”

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Transcript:

Mikki:

Dr. Hoskins, can ovarian cancer be hereditary? Should patients suggest that their family members undergo genetic testing?

Dr. Ebony Hoskins:

So, yes, ovarian cancer can be hereditary. Approximately 10 to 15 percent are associated with an increased risk with family history. It is now recommended that any patient with ovarian cancer get genetics testing period, even if there’s no family history that they should be offered genetics testing. I always recommend that an affected person, when I say affected person, I mean the person that have the cancer diagnosis get the genetics testing first. So sometimes I see patients where they’re…have several family members with, say, breast cancer, which could be indicative of a breast like a BRCA mutation, which is associated with an ovarian cancer. And come to find out they’ve had genetics testing, but they don’t have the gene for ovarian cancer. So again, it’s important that the affected person, meaning the person that have the cancer, get genetics testing. My activation tip for this is if you know someone who has ovarian cancer or if you’re affected yourself, make sure you have gotten genetics testing standard of care. 

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How Do Genomic Testing Results Impact Breast Cancer Treatment Options?

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How Do Genomic Testing Results Impact Breast Cancer Treatment Options? from Patient Empowerment Network on Vimeo.

Understanding a breast cancer patient’s individual disease is vital to personalizing their care. Dr. Jame Abraham explains how genomic testing results could impact a patient’s treatment path.

Dr. Jame Abraham is the chairman of the Department of Hematology & Medical Oncology at Cleveland Clinic and professor of medicine at Cleveland Clinic Lerner College of Medicine. Learn more about Dr. Abraham.

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Transcript:

Katherine:

Dr. Abraham, how do genomic test results impact treatment options?  

Dr. Abraham:

So, let’s just kind of think about the germline mutation. Let’s just say, we do a genetic testing for a patient with a stage two breast cancer. And let’s just say, if the patient has BRCA1 mutation, basically, we are saying, if somebody has a BRCA1 mutation, there’s about a 20 to 40 percent chance of developing contralateral breast cancer, breast cancer on the other side, and then, about 20 to 40 percent chance of developing ovarian cancer. 

So, if I’m seeing somebody who is in their 40s or 50s, those who completed their family, completed the family, then, with the mutation, we will talk to them about potential risk reduction surgeries for the other breast. 

And then, in addition, we’ll talk about removing the ovaries for prevention of ovarian cancer. 

So, that’s one major decision point. And then, let’s just say, with the BRCA mutation, there are new drugs, FDA-approved, what we call as, PARP inhibitors, or olaparib (Lynparza). After completing their chemotherapy and other treatments, we can add a PARP inhibitor or olaparib to their adjuvant treatment. That means, after surgery and chemo, we can add this medicine, for their treatment, for a year. 

So, this has tremendous implications for their treatment. And then, let’s just say, if she has other family members, there’s about 50 percent chance that they may have the same. 

So, you can probably talk to them about doing the testing for them, and that may influence their screening methods, to see if she has kids, and what 50 percent chance that they can inherit this gene. Again, that can influence how we screen and manage them.  

So, let’s just say, if I’m seeing somebody who stage I breast cancer, you’re positive, and then, we do a genomic testing. It’s not exactly somatic, but it’s, still, it’s a genomic testing. 

So, we do a genomic testing, such as Oncotype, or MammaPrint – so, again, that’s an early-stage breast cancer – that specifically looked at certain things within the tumor, which are markers for proliferation. So, those tests will help us, again, in a specific subset of patients, ER-positive, HER2-negative, early-stage patients, tests, such as Oncotype and MammaPrint, will help us to identify who will need chemo, or whom we can spare more aggressive treatments like chemo. 

And then, in metastatic setting, when we do this testing, we can see certain mutations within the tumor that will allow us to recommend treatments based upon that. 

What Are Some Hereditary Factors Impacting Prostate Cancer Patients?

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What Are Some Hereditary Factors Impacting Prostate Cancer Patients? from Patient Empowerment Network on Vimeo.

Along with aging, hereditary factors also contribute to prostate cancer incidence. Expert Dr. Leanne Burnham details some of the hereditary factors, their mechanism of action, and some treatments under study in prostate cancer clinical trials for African American men.

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Transcript:

Dr. Leanne Burnham

So, cancer is a disease of aging, and cancer is a hereditary disease for a lot of different kinds of cancers, not all, but for a lot of them. And so prostate cancer is one of those that we know for sure that there are some genetic variations that are passed down from our parents that would make men either predisposed or not to get prostate cancer and also would predispose them to get aggressive prostate cancer.

And so, for example, if you have a father, an uncle, grandfather, if you have family members that have had prostate cancer, and beyond that, if you had women in your family that have had breast cancer, then that increases your chance as a man to get prostate cancer and to get it even younger than other races would. And so certain things that we look at in the lab and in the clinic at City of Hope are really trying to understand what those hereditary factors are, and then how you can target them with drug treatments specifically.

So, for example, we have a clinical trial that a team of us developed, and we are looking at the ability of something called PARP inhibitor not to get too technical with you, but PARP inhibitors, if you want to Google it, they are at the forefront of prostate cancer treatments right now, and especially a few running in clinical trials. And so there is a hereditary disposition, there is a mutation on the BRCA gene that leads to PARP inhibitors benefiting any person that would have that BRCA mutation.

What we’re doing in our clinical trial is we are using a PARP inhibitor called talazoparib (Talzenna), and we are not only providing that to patients that have the spark commutation, but we are extending it to patients that may not have that mutation, and the reason for is because, and I definitely don’t want to get crazy technical, but the reason for it in a nutshell, as we know in cancer there is an interaction between PARP inhibition and androgen receptor function and reaction to treatments. And so, you may have heard of androgen and androgen receptor when it comes to prostate cancer, it’s really the fancy way of saying testosterone, and prostate cancer needs testosterone, or it needs androgen and androgen receptor to function and to grow. And so, what we want to see in this clinical trial is if we target, if we use PARP inhibitors in combination with hormone therapy that’s targeting androgen production androgen receptor, will we see better treatment and better response to the drugs in those patients. And the extra cool part to me is we know that there are variations in DNA segments that affect androgen receptor function in African American men. And so, for a specific mechanism that I won’t dive into, it involves trinucleotide repeats and link, segments links and all this, but because of these variations and androgen receptor in African American men that we know was associated with their ancestry and what they’ve inherited in their own DNA, this drug should work better in African American men. And we will be able to tease that out in this clinical trial. So, it’s an opportunity for African American men who have prostate cancer who have not developed castration resistance yet, but who do have metastatic prostate cancer so, at that point, there is not a cure, right, and so you can go to your physician, and you can get a standard of care therapy, or you may want to consider this clinical trial where you would receive standard care therapy. And then also, as I said before this VIP access to this new drug, this PARP inhibitor that we think may improve outcomes in men.