Triple-negative breast cancer represents approximately 15 percent of all breast cancers, but it is diagnosed at a higher rate in patients with hereditary (particularly BRCA1-gene associated) breast cancer, as well as among African-American women.
In this segment, Yuan Yuan, MD., Ph.D. discusses this aggressive form of breast cancer and how City of Hope is leading the field in advancements for this type of cancer and how there are several innovative clinical trials both for newly diagnosed and Stage 4 triple negative breast cancer patients that play into efforts going on nationally to address these difficult to treat tumors.
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Metastatic Triple Negative Breast Cancer
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Learn more about Yuan Yuan, MD., Ph.D
Yuan Yuan, MD, PhD
Yuan Yuan, MD., Ph.D. is an assistant professor specializing in breast oncology in the Department of Medical Oncology & Therapeutics. Prior to joining City of Hope in 2012, she was an assistant professor at Loma Linda University Medical Center in the Division of Medical Oncology and Hematology, and a principal investigator for multiple breast cancer trials.Learn more about Yuan Yuan, MD., Ph.D
Transcription:
Metastatic Triple Negative Breast Cancer
Melanie Cole (Host): Although breast cancer is often referred to as one disease; there are actually many different types. The differences can help guide treatment and provide information on prognosis. Certain characteristics make some breast cancers more aggressive than others. One such breast cancer is metastatic triple negative breast cancer. My guest today is Dr. Yuan Yuan. She is an assistant professor specializing in breast oncology in the Department of Medical Oncology and Therapeutics at City of Hope. Welcome to the show Dr. Yuan. What is metastatic triple negative breast cancer?
Dr. Yuan Yuan, MD, PhD (Guest): Thank you. Triple negative breast cancer is defined by lack of three receptors; estrogen receptor, progesterone receptor and HER2 receptors. So, that defines the triple negative breast cancer and so called the metastasis meaning the tumor had traveled beyond the local, went to other organ systems. So, triple negative breast cancer of course is one of the most challenging and aggressive disease.
Melanie: So, when we hear the word metastases, we think that as you say, it has traveled to other areas, but people tend to think of that as something that you find later in a cancer. So, is this something that happens very quickly in this cancer?
Dr. Yuan: Yes. The tumor is characterized by dividing really fast. We use the jargon called a proliferation means the tumor grows, they divide from one to two, two to four really fast. So, that it gets higher chance of spread beyond local and the most common sites of metastases can be liver, lung, brain. So, these are the really vital organs that we survive on.
Melanie: So, who would be a risk for this type of breast cancer?
Dr. Yuan: Any woman, but it tends to happen in certain ethnic backgrounds such as African Americans, Hispanics and also it happens in younger women.
Melanie: It happens in younger women? So, that’s a little bit more rare, now as we are getting our mammograms and some women don’t start until thirty five or forty, then is this a breast cancer that might have a genetic component that might signal that you want to start getting those mammograms earlier?
Dr. Yuan: Yes. Anyone who has family history of early onset breast cancers, I would encourage them to look for genetic counseling and often triple negative breast cancer is tied into the connection between the BRCA1 mutation and nowadays because of what we have much more comprehensive genetic testing panels we are able to identify gene mutations beyond the BRCA1 and 2.
Melanie: So, then what is treatment like? Are we in the clinical trial phase? Are there a lot of things that you are doing? Or is there a standard course of treatment that has been set out for this particular type?
Dr. Yuan: Yes, so over the past years, there has been a lot of effort to look into treatment options beyond chemotherapy. But unfortunately, at this moment of time, there is no FDA approved target therapy beyond conventional chemo. There has been a lot of efforts in research, such as identifying newer targets, identification of immunotherapies, so at this moment of time, we do have multiple clinical trials in triple negative breast cancer and as you mentioned earlier, breast cancer is heterogenous and in triple negative breast cancer, it is also a very heterogenous disease including a multiple of subset types, that is based on a MRNA expression panel, so at this time, we are working hard to identify a subset of triple negative breast cancer and treat them accordingly. We have multiple clinical trials for example, one of the trials we are leading is to target androgen receptor positive triple negative which accounts for about 10% of triple negatives and we combine immunotherapy with a checkpoint inhibitor and with the androgen receptor targeting drug which is an oral agent. So, that is one of the efforts that we are leading right now. We have multiple other studies and trying to identify targets, but the disease has been very challenging to treat especially in the metastatic setting because of the previous therapies they have received; so, the tumor often becomes chemotherapy resistant.
Melanie: And what about hormone therapy? Is it as resistant to that as it might be to chemo?
Dr. Yuan: Yes, because of a lack of receptors, ER and PR so hormonal therapy conventionally was not offered and here in this clinical trial, I mentioned earlier, we are looking at androgen receptors which is a male hormone receptor we can identify in about 10% of triple negative patients and we are hoping to see signals. Now there are some earlier trials utilizing drugs such as enzalutamide which we use to treat prostate cancer because of the prostate cancer cells expressed androgen receptors. So here in this clinical trial, we are using that concept and that concept has been tested but the signal is not super robust. For example, response rate is around 15-20% when you are just giving patient hormonal therapy. So, here in this clinical trial, we are combining hormonal therapy, antihormonal therapy and antiandrogen receptor with antiPD1 inhibitors. So, we are hoping to see some synergies between these two.
Melanie: So, as far as immunotherapy goes and seeing what is going on out there, is there – there is a new medication that might be effective in shrinking the tumors? Are you working on that immunotherapy as well?
Dr. Yuan: Yes. So, one of these agents being tested is called pembrolizumab or Keytruda. Earlier clinical trial has demonstrated a single agent activity meaning by offering just the single agent, Keytruda, alone in triple negative breast cancer, the response rate is around 8-15% of the time and one of the trials it is actually 19%, but we think it is not good enough and often our patients do have very aggressive disease and you need a much more effective therapy in order to help them relieve the symptoms and to prolong the survival. So, that is why the combination strategy has been utilized here. So, beyond the androgen receptor targeting drug, we also have a combination using Keytruda in combination doxorubicin, one of my colleagues is leading that study. Another trial is using Keytruda in combination with a stem cell inhibitor called Axl, A-X-L, axl inhibitor, so that is an ongoing study we just opened and looking forward to seeing some positive signals.
Melanie: So, what about recurrence and survival? We don’t always like to talk about prognosis and survival on this show, however, this one sort of warrants that. Is it a highly, does it recur quite often and then when it does, is it much harder to treat?
Dr. Yuan: Yes. So, the recurrence rate for stage by stage comparing the ER positive disease or HER2 positive disease to what is triple negative, the triple negative patients have a much higher rate of recurrence and once patients were diagnosed stage four or metastatic, the overall survival is really pretty bad in a way that average survival is about 13 months.
Melanie: So, what can you tell women Dr. Yuan, if they are either at risk for this type of breast cancer or if they have been diagnosed, what would you like them to know that might give them some hope and things that you are doing there at City of Hope?
Dr. Yuan: Yes. So, for women who have a diagnosis with any type of breast cancer, I think the key is to keep a very close follow up on a regular basis with their oncologist and certainly for triple negative, the challenge is that we don’t have a good adjuvant therapy, so although there are some clinical trials that are looking into giving women immunotherapy in the adjuvant setting, but that is not a proven strategy but a woman can certainly do several things to reduce their risk of recurrence. One such strategy is exercise and weight reduction has in some areas has shown benefit, but most important thing is that to keep a close follow up with your oncologist. And at this time, for the adjuvant patient, we are bringing some newer clinical trials to try to help for high risk women to offer them different options. Outside of that setting, we don’t have a lot of effective strategies. But for recurrent or metastatic cases, I think certainly looking for immunotherapy combinations would be something probably the most promising area in treating metastatic breast cancer – triple negative breast cancer, in addition at City of Hope, we are doing robust research including the preclinical translational and early phase clinical trials in an effort to try to change the current status of lack of therapy for triple negative breast cancer. So please do consider participating in one of our studies.
Melanie: Thank you so much Dr. Yuan for being with us today. You are listening to City of Hope Radio and for more information, you can go to cityofhope.org. That’s cityofhope.org. This is Melanie Cole. Thanks so much for listening.
Metastatic Triple Negative Breast Cancer
Melanie Cole (Host): Although breast cancer is often referred to as one disease; there are actually many different types. The differences can help guide treatment and provide information on prognosis. Certain characteristics make some breast cancers more aggressive than others. One such breast cancer is metastatic triple negative breast cancer. My guest today is Dr. Yuan Yuan. She is an assistant professor specializing in breast oncology in the Department of Medical Oncology and Therapeutics at City of Hope. Welcome to the show Dr. Yuan. What is metastatic triple negative breast cancer?
Dr. Yuan Yuan, MD, PhD (Guest): Thank you. Triple negative breast cancer is defined by lack of three receptors; estrogen receptor, progesterone receptor and HER2 receptors. So, that defines the triple negative breast cancer and so called the metastasis meaning the tumor had traveled beyond the local, went to other organ systems. So, triple negative breast cancer of course is one of the most challenging and aggressive disease.
Melanie: So, when we hear the word metastases, we think that as you say, it has traveled to other areas, but people tend to think of that as something that you find later in a cancer. So, is this something that happens very quickly in this cancer?
Dr. Yuan: Yes. The tumor is characterized by dividing really fast. We use the jargon called a proliferation means the tumor grows, they divide from one to two, two to four really fast. So, that it gets higher chance of spread beyond local and the most common sites of metastases can be liver, lung, brain. So, these are the really vital organs that we survive on.
Melanie: So, who would be a risk for this type of breast cancer?
Dr. Yuan: Any woman, but it tends to happen in certain ethnic backgrounds such as African Americans, Hispanics and also it happens in younger women.
Melanie: It happens in younger women? So, that’s a little bit more rare, now as we are getting our mammograms and some women don’t start until thirty five or forty, then is this a breast cancer that might have a genetic component that might signal that you want to start getting those mammograms earlier?
Dr. Yuan: Yes. Anyone who has family history of early onset breast cancers, I would encourage them to look for genetic counseling and often triple negative breast cancer is tied into the connection between the BRCA1 mutation and nowadays because of what we have much more comprehensive genetic testing panels we are able to identify gene mutations beyond the BRCA1 and 2.
Melanie: So, then what is treatment like? Are we in the clinical trial phase? Are there a lot of things that you are doing? Or is there a standard course of treatment that has been set out for this particular type?
Dr. Yuan: Yes, so over the past years, there has been a lot of effort to look into treatment options beyond chemotherapy. But unfortunately, at this moment of time, there is no FDA approved target therapy beyond conventional chemo. There has been a lot of efforts in research, such as identifying newer targets, identification of immunotherapies, so at this moment of time, we do have multiple clinical trials in triple negative breast cancer and as you mentioned earlier, breast cancer is heterogenous and in triple negative breast cancer, it is also a very heterogenous disease including a multiple of subset types, that is based on a MRNA expression panel, so at this time, we are working hard to identify a subset of triple negative breast cancer and treat them accordingly. We have multiple clinical trials for example, one of the trials we are leading is to target androgen receptor positive triple negative which accounts for about 10% of triple negatives and we combine immunotherapy with a checkpoint inhibitor and with the androgen receptor targeting drug which is an oral agent. So, that is one of the efforts that we are leading right now. We have multiple other studies and trying to identify targets, but the disease has been very challenging to treat especially in the metastatic setting because of the previous therapies they have received; so, the tumor often becomes chemotherapy resistant.
Melanie: And what about hormone therapy? Is it as resistant to that as it might be to chemo?
Dr. Yuan: Yes, because of a lack of receptors, ER and PR so hormonal therapy conventionally was not offered and here in this clinical trial, I mentioned earlier, we are looking at androgen receptors which is a male hormone receptor we can identify in about 10% of triple negative patients and we are hoping to see signals. Now there are some earlier trials utilizing drugs such as enzalutamide which we use to treat prostate cancer because of the prostate cancer cells expressed androgen receptors. So here in this clinical trial, we are using that concept and that concept has been tested but the signal is not super robust. For example, response rate is around 15-20% when you are just giving patient hormonal therapy. So, here in this clinical trial, we are combining hormonal therapy, antihormonal therapy and antiandrogen receptor with antiPD1 inhibitors. So, we are hoping to see some synergies between these two.
Melanie: So, as far as immunotherapy goes and seeing what is going on out there, is there – there is a new medication that might be effective in shrinking the tumors? Are you working on that immunotherapy as well?
Dr. Yuan: Yes. So, one of these agents being tested is called pembrolizumab or Keytruda. Earlier clinical trial has demonstrated a single agent activity meaning by offering just the single agent, Keytruda, alone in triple negative breast cancer, the response rate is around 8-15% of the time and one of the trials it is actually 19%, but we think it is not good enough and often our patients do have very aggressive disease and you need a much more effective therapy in order to help them relieve the symptoms and to prolong the survival. So, that is why the combination strategy has been utilized here. So, beyond the androgen receptor targeting drug, we also have a combination using Keytruda in combination doxorubicin, one of my colleagues is leading that study. Another trial is using Keytruda in combination with a stem cell inhibitor called Axl, A-X-L, axl inhibitor, so that is an ongoing study we just opened and looking forward to seeing some positive signals.
Melanie: So, what about recurrence and survival? We don’t always like to talk about prognosis and survival on this show, however, this one sort of warrants that. Is it a highly, does it recur quite often and then when it does, is it much harder to treat?
Dr. Yuan: Yes. So, the recurrence rate for stage by stage comparing the ER positive disease or HER2 positive disease to what is triple negative, the triple negative patients have a much higher rate of recurrence and once patients were diagnosed stage four or metastatic, the overall survival is really pretty bad in a way that average survival is about 13 months.
Melanie: So, what can you tell women Dr. Yuan, if they are either at risk for this type of breast cancer or if they have been diagnosed, what would you like them to know that might give them some hope and things that you are doing there at City of Hope?
Dr. Yuan: Yes. So, for women who have a diagnosis with any type of breast cancer, I think the key is to keep a very close follow up on a regular basis with their oncologist and certainly for triple negative, the challenge is that we don’t have a good adjuvant therapy, so although there are some clinical trials that are looking into giving women immunotherapy in the adjuvant setting, but that is not a proven strategy but a woman can certainly do several things to reduce their risk of recurrence. One such strategy is exercise and weight reduction has in some areas has shown benefit, but most important thing is that to keep a close follow up with your oncologist. And at this time, for the adjuvant patient, we are bringing some newer clinical trials to try to help for high risk women to offer them different options. Outside of that setting, we don’t have a lot of effective strategies. But for recurrent or metastatic cases, I think certainly looking for immunotherapy combinations would be something probably the most promising area in treating metastatic breast cancer – triple negative breast cancer, in addition at City of Hope, we are doing robust research including the preclinical translational and early phase clinical trials in an effort to try to change the current status of lack of therapy for triple negative breast cancer. So please do consider participating in one of our studies.
Melanie: Thank you so much Dr. Yuan for being with us today. You are listening to City of Hope Radio and for more information, you can go to cityofhope.org. That’s cityofhope.org. This is Melanie Cole. Thanks so much for listening.