Tag Archive for: mismatch repair status

Endometrial Cancer Biomarkers | Impact on Prognosis and Treatment

What are endometrial cancer biomarkers? Dr. Hinchcliff discusses how prognostic biomarkers, namely mismatch repair status and HER2, influence treatment, leading to more tailored strategies for patients.  

Dr. Emily Hinchcliff is a Gynecologic Oncologist at Northwestern Medicine. Learn more about Dr. Hinchcliff.

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See More from INSIST! Endometrial Cancer

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Essential Endometrial Cancer Testing

Essential Endometrial Cancer Testing

What Questions Should Patients Ask About Endometrial Cancer Testing?What Questions Should Patients Ask About Endometrial Cancer Testing? Endometrial Cancer | What Is Personalized Medicine?

Endometrial Cancer | What Is Personalized Medicine?

Transcript: 

Katherine Banwell: 

Are there prognostic biomarkers that help determine how the cancer may behave? 

Dr. Emily Hinchcliff:  

Yeah. So, endometrial cancer, we now know that the molecular mechanism – so, what I’ve been talking about, these things that are happening inside the cancer cell – we now know that that can drive prognosis, and so, it used to be that we kind of had two big buckets of cancer. 

We used to say there’s Type 1 endometrial cancer and Type 2 endometrial cancer, and now, we’ve actually broken it down into molecular categories – so, into categories much more based on certainly what the cell looks like under the microscope, but also what’s going on inside the cell, not only to impact treatment, but also to give a patient a better look at what their prognosis is expected to potentially be, and we actually have changed our staging system pretty recently to incorporate some of those molecular characteristics that we now know to check for.  

Katherine Banwell:  

Talking about the biomarkers, how do biomarkers impact endometrial cancer treatment options? 

Dr. Emily Hinchcliff:  

Yeah, so I think specifically the two that I mentioned, the mismatch repair status and the HER2 status, have really robust data that tells us that we can better tailor our treatment strategy based on a patient’s status. So, for mismatch repair, for example, if someone is mismatch repair deficient, that tumor is going to respond very well, incredibly well, to immunotherapy. So, we now actually use immunotherapy in combination with chemotherapy to treat those cancers, especially for the cancers that have spread outside the uterus or the cancers that have gone through initial treatment and then come back. 

So, I think that is a really great option. Similarly, that HER2 receptor, there is a medicine that targets that receptor, which is that cell surface molecule, that thing that’s sitting on the cancer surface, and can treat that cancer better if that marker is expressed. 

Essential Endometrial Cancer Testing

 

What testing should endometrial cancer patients undergo after diagnosis? Dr. Hinchcliff explains the importance of determining cancer stage, histology, and performing biomarker testing, as these factors can guide more targeted treatments.

Dr. Emily Hinchcliff is a Gynecologic Oncologist at Northwestern Medicine. Learn more about Dr. Hinchcliff.

Download Resource Guide

See More from INSIST! Endometrial Cancer

Related Resources:

What Questions Should Patients Ask About Endometrial Cancer Testing?What Questions Should Patients Ask About Endometrial Cancer Testing? Endometrial Cancer Biomarkers | Impact on Prognosis and Treatment

Endometrial Cancer Biomarkers | Impact on Prognosis and Treatment

Endometrial Cancer | What Is Personalized Medicine?

Endometrial Cancer | What Is Personalized Medicine?

Transcript: 

Katherine Banwell:   

Dr. Hinchcliff, what testing should people with endometrial cancer undergo after diagnosis? 

Dr. Emily Hinchcliff:  

So, when I think about a cancer diagnosis, there are first two big buckets of things that are important to understand. One is the cancer stage, meaning where did the cancer start, and then, where has it potentially spread to. The other is the cancer histology, or what do the cells look like under the microscope. And in endometrial cancer, there are actually a variety of different subtypes of endometrial cancer that can be differentiated based on what they look like under the microscope. Once you have those as your framework, I think the next step is to better understand what’s called biomarker testing, or the genetics of your cancer. 

Katherine Banwell:  

Would you define biomarker testing? What does that mean? 

Dr. Emily Hinchcliff:  

Yeah. So, biomarker testing – while, under the microscope, we can determine what kind of cancer something is, we can’t tell what’s going on inside the cancer cells itself, and so, biomarker testing is an umbrella term for a variety of different tests that really try and assess what’s going on inside the cancer, what are the genetics making the cancer cells divide and grow abnormally, and also, what are the things that might be expressed or on the cancer cell surface that are potentially targets for us to leverage to treat the cancer better. So, what is unique to that cancer, either the patient’s own cancer individually or that cancer type in general, that we can use to our benefit to treat the cancer better.  

Katherine Banwell:  

What are the most common biomarkers associated with gynecologic cancers?  

Dr. Emily Hinchcliff:  

So, in endometrial cancer specifically, I think if there are a couple take-homes that I can emphasize to patients in this talk today, the first is it is essential to know your what’s called mismatch repair status. So, mismatch repair is one of the things that can happen inside a cancer cell, and when that goes awry, when that becomes abnormal, it means that the cancer has particular features that we can use to treat it better. 

And so, the two categories of mismatch repair are you can be mismatch repair deficient, meaning there’s something abnormal in that machinery inside the cancer cell, or mismatch repair proficient, meaning that that machinery is still intact, and the reason for that being so important is that in endometrial cancer, if someone’s cancer is mismatch repair deficient, we can use a whole class of drugs called immunotherapy, or leveraging your own immune system using medicines to try and treat that cancer better. 

So, I think knowing that about your cancer type is really essential in endometrial cancer. I think the other thing that is important to know is in endometrial cancer, some subsets will express a receptor – so basically, something on the cancer surface – called HER2, and if you are HER2-positive, that also can be a target for potential drugs. So, those are two really important biomarkers in endometrial cancer that I think it’s important that patients know that they have been tested, and then know what their results are. 

Overcoming Barriers: Empowering Underrepresented Groups With Endometrial Cancer

Overcoming Barriers: Empowering Underrepresented Groups with Endometrial Cancer from Patient Empowerment Network on Vimeo.

 How can endometrial cancer care barriers be overcome for underrepresented groups? Expert Dr. Emily Hinchcliff from Northwestern Medicine discusses racial and cultural barriers and advice to patients to be proactive toward receiving optimal care.

[ACT]IVATION TIP

“…know the genetic status of your tumor, specifically something called the mismatch repair status of your tumor. And then not only how does that status impact your own treatment, but also how that may impact your family members…understand what resources are out there for you as a patient, especially for women in underserved groups and minority populations.”

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See More from [ACT]IVATED Endometrial Cancer

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Overcoming Geographical Barriers in Endometrial Cancer Care

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Innovative Approaches to Endometrial Cancer Care in Underrepresented Communities

Innovative Approaches to Endometrial Cancer Care in Underrepresented Communities

Endometrial Cancer Care Disparities | The Impact of Rural Residence

Endometrial Cancer Care Disparities: The Impact of Rural Residence

Transcript:

Lisa:

Dr. Hinchcliff, in your research, you dive deeply into the significant disparities that exist within medically underserved and minority populations in the U.S. when it comes to awareness of, access to, and the use of genetic services in endometrial cancer. Can you speak to the research and provide tips to these patients and families?

Dr. Emily Hinchcliff: 

Yeah, so I think that there are sort of two different pieces that go on here. First is the relationship of endometrial cancer, that some of it can be, I guess, at random, and some of it can be genetic. So understanding, especially for those who have a strong family history, that there are hereditary forms of endometrial cancer. I think that’s a really important point for patients to take away. And then we, as a society, as a field, now recommend kind of routine screening for those tests to determine, Is an endometrial cancer hereditary or not? So make sure that you, as a patient, know your results and know if your family members should be tested in any way.

The second is regarding the significant disparities that exist. We know, as a field, as a kind of medical subspecialty, that there is a racial disparity in endometrial cancer mortality. While there is a lot of research going on to address the kind of potential biologic component there, is there something different about the cancers that are developed in different racial groups? I think there’s also really important research going on about the kind of systemic and cultural barriers and differences that women of different races experience that also can dramatically impact their cancer care.

Lisa:

And do you have an activation tip for this question?

Dr. Emily Hinchcliff:  

I’ll give you two different activation tips. I think that the first is to know the genetic status of your tumor, specifically something called the mismatch repair status of your tumor. And then not only how does that status impact your own treatment, but also how that may impact your family members. And then I think the second is to understand what resources are out there for you as a patient, especially for women in underserved groups and minority populations. Simply obtaining support can often be a really important key first step to gaining access and understanding of your disease.


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Colon Cancer Treatment and Research News

Colon Cancer Treatment and Research News from Patient Empowerment Network on Vimeo.

What’s the latest colon cancer treatment and research news from the American Society of Clinical Oncology (ASCO) meeting? Dr. Smitha Krishnamurthi shares updates about research findings that were presented at the meeting along with exciting ongoing research in colon cancer.

Dr. Smitha Krishnamurthi is a gastrointestinal medical oncologist at the Cleveland Clinic. Learn more about Dr. Krishnamurthi here.

See More From The Pro-Active Colon Cancer Patient Toolkit


Related Resources:

Should Your Family Members Be Screened for Colon Cancer?


Transcript:

Katherine Banwell:

Welcome, Dr. Krishnamurthi. Would you mind Would you mind introducing yourself?  

Dr. Krishnamurthi:

Sure, it’s my pleasure. Thank you for having me, Katherine. I’m Smitha Krishnamurthi. I’m a medical oncologist. I specialize in taking care of patients who have colorectal cancer and other gastrointestinal cancers. As a medical oncologist, I treat patients with drug therapy like chemotherapy and immunotherapy.  

Katherine Banwell:

And where are you located?  

Dr. Krishnamurthi: I work at Cleveland Clinic in Cleveland, Ohio. 

Katherine Banwell:

Excellent. Thank you so much.  

Cancer researchers came together recently to share findings at the annual American Society of Clinical Oncology meeting, also known as ASCO. Are there highlights from the meeting that patients should know about?  

Dr. Krishnamurthi:

Yes. That’s always such an amazing gathering of knowledge. Thankfully, it’s continued virtually at least due to the pandemic. This past ASCO last month, some of the major highlights in colorectal cancer were the final overall survival results were presented from the study of pembrolizumab versus chemotherapy as first-line treatment for patients with metastatic colorectal cancer with deficient mismatch repair or MSI high status.  

These are the patients who are predicted to benefit from immunotherapy.  

We’d already seen earlier results that the patients who received the immunotherapy up front had a much-improved time for the cancer to regress. Here, they presented the overall survival results, which showed that the median survival for patients who received chemotherapy was three years, meaning half the patients lived shorter time, half lived longer. For the patients who received the pembrolizumab, they hadn’t even reached the median survival at five years.  

So, it looks very important that we know this MSI status or mismatch repair status from the beginning, so that we can offer the right patients immunotherapy first.  

Other highlights were, for example, for patients who have cancers that overexpress HER2/neu. It’s an oncogene. When it’s overexpressed, it tends to drive growth of cancers.  

 We don’t have any FDA-approved drugs for HER2-amplified colorectal cancer, but there are many studies showing that those patients with that type of cancer benefit from targeting this HER2 protein. There are, of course, approved drugs for HER2/neu-amplified breast cancer and stomach cancer. One of these drugs is trastuzumab deruxtecan.   

It’s a drug that targets the HER2/neu protein, but it’s connected with chemo. So, it’s like bringing chemo right to the tumor. The results showed a very high response rate. But it does have a peculiar toxicity of causing inflammation in the lung. So, it’s another treatment option that could be approved. It’s good to see that we’re getting more treatment options there. 

Katherine Banwell:

What are you excited about when it comes to colon cancer research? 

Dr. Krishnamurthi:

There are so many important questions we still need to learn the answers to. I find that patients who have, of course, a mutation of the KRAS or NRAS gene and have metastatic cancer, they have fewer treatment options than when those genes are normal. 

KRAS is a very important oncogene driver of cancer in colorectal cancer, but also in lung cancer and pancreatic cancer. For many decades, it was thought that there was no way to target this protein. Now, we’re seeing that there’s a certain type of KRAS mutation – KRAS G12C – that can be targeted with drugs that now are approved in lung cancer. 

It’s a small fraction of colorectal cancer patients who have that mutation, but it’s like we’re beginning to crack this code. The most common KRAS mutation is G12D. There is a company – Mirati – that has a candidate G12D inhibitor that’s going to enter clinical trials this year. It’s very exciting.   

There was recently a press release onvansertib, which is a polo-like kinase inhibitor, combined with chemotherapy, a second-line treatment for patients with KRAS-mutant colon cancer, showing a much higher response rate than we would expect with the chemotherapy alone.  

That will need to be validated in a large, randomized trial, but that’s looking very exciting. Then the other aspects that I’m most excited about are how to get immunotherapy to work for more of our patients.   

We know that patients who have abnormal mismatch repair or MSI-high cancers can benefit remarkably in the metastatic setting and there are studies going on in the early-stage setting and there are reports of it looking quite promising. But how do we get it to work for the majority of patients who have normal DNA mismatch repair or MSS, microsatellite stable cancers? That’s an area of great interest.  

We’ve seen a study in the Netherlands where they treated patients with normal DNA mismatch repair, early-stage colon cancer, with just two doses of immunotherapy before going to surgery for their early-stage cancer. I was surprised to see like four out of 15 patients responded to the treatment. Perhaps earlier stage cancers may be more responsive to immunotherapy. Definitely looking forward to more updates from that study, which we’ll probably hear in the fall at the European Society of Medical Oncology meeting in fall of 2021. 

Then, of course, the other area that really interests me is what is causing this epidemic of colorectal cancer in young adults? This is really a matter of laboratory studies and epidemiologic studies, but that’s also an area of great interest.  

Katherin Banwell:

There’s an epidemic among younger people?  

Dr. Krishnamurthi:

Yeah. I think of it as an epidemic in that colorectal cancer has definitely been increasing in young Americans and young people around the world in many countries.  

Basically, clearly, there’s been an increase since the 1980s. It seems to be something environmental because it’s related to time. So, it’s not inherited. Some of our patients below the age of 50 diagnosed with colorectal cancer do not have an inherited cause. A study from Ohio State found that 16 percent have an inherited cause. So, 84 percent of them do not. This is definitely increasing, particularly of rectal cancer. I think it must be something environmental. Possibly something like we’re ingesting because our colon is exposed to what we eat. But we really don’t know yet.  

And so, I just advise all my patients and everyone who is interested to just try to eat as much natural food as we can. To try to minimize processed foods and chemicals. 

Because I think that’s the best we can do until we really identify the cause.