How Neoadjuvant Therapy Has Improved Breast Cancer Care
Guest
: Harry Bear, MD, PhD
From the Show: VCU Health System
Some breast cancer may allow for pre-surgical treatment. Dr. Harry Bear, Chair of Surgical Oncology at VCU Massey Cancer Center, discusses neoadjuvant therapy for breast cancer.
Transcription:
Alyne Ellis (Host): Breast cancer. Sometimes you can have a less radical surgery if you have chemo before the operation. Here to tell us about how this preop treatment works is Dr. Harry Bear, Chair of Surgical Oncology at VCU Massey Cancer Center. Welcome to Healthy with VCU Health. I’m Alyne Ellis. Dr. Bear, thanks for joining me. What is neoadjuvant therapy and how is it used to treat breast cancer?
Harry Bear, M.D., Ph.D. (Guest): So, the concept of using neoadjuvant therapy, which is giving a systemic therapy usually either chemotherapy or hormonal therapy prior to the surgical management of a breast cancer or any other cancer for that matter, really began in the 70s when we were confronted with patients who had cancers that were virtually inoperable. In other words, it wasn’t even possible to surgically remove the tumor with even a radical mastectomy.
Unfortunately, in those days, the drugs that we had available to us were not very effective, and so, even though it was the only option, it was not always terribly successful, but it could sometimes convert patients from being inoperable to operable. In the mid-80s, a number of researchers, including us at Massey, began exploring the approach of using this treatment in operable breast cancer patients – neoadjuvant therapy given before the surgery rather than after. And we learned that it was equally effective as giving the same drugs after surgery in terms of the patient’s overall survival. But it had a number of important advantages particularly for patients who would have otherwise required removal of the entire breast. Many of those patients could be converted to breast conservation surgery or a lumpectomy. In addition, more recently, we’ve learned that we can reduce the scope or the radicalness of the lymph node surgery in some patients who have positive nodes or may have positive nodes at the time they are diagnosed. We may not have to remove all their lymph nodes like we used to in the past.
Host: And if you do this treatment before surgery, does that open up other options after the surgery is over?
Dr. Bear: Well that’s really been the most recent benefit of the neoadjuvant approach. As we were investigating neoadjuvant therapy, we gathered convincing evidence that the response to treatment – in other words, how effectively the treatment shrank the tumor and sometimes to the point where there was no cancer left in the breast or in the lymph nodes at the time of surgery – was very predictive of how the patients were going to do long term.
So, patients whose cancers disappeared with the neoadjuvant treatment did very well, and patients who had even a little cancer left behind at the time of surgery had a much less good outcome and were much more likely to recur and die of their disease. And for a long time, there wasn’t a whole lot we could do about that. But more recently, particularly for triple negative breast cancers and for HER2 positive breast cancers, where we combine neoadjuvant chemotherapy with HER2 targeted therapy, we’ve discovered just in the last year or so, that giving certain additional treatments to patients with residual cancer has dramatically improved their prognosis and their likelihood of being cured.
So, now, this has become a valuable tool to assess whether the patient is very responsive to standard therapy and will do quite well or doesn’t respond so well to the standard-of-care therapy and needs something added. In some cases, the added therapy can improve their outlook. In addition, it provides a platform for doing clinical trials of new treatments where we try the new treatments on patients who have a very guarded or very grim prognosis and hopefully be able to improve that prognosis, such as adding immunotherapy for triple negative breast cancers that have an incomplete response to neoadjuvant chemotherapy.
Host: So, which breast cancer patients are eligible for neoadjuvant therapy?
Dr. Bear: Almost all patients with a HER2 positive breast cancer, unless it’s very, very tiny. Most patients or many patients with what we call triple negative breast cancer, that is breast cancer that does not respond to hormones and is not HER2 amplified or HER2 positive. Any patient with positive nodes should be considered for neoadjuvant therapy. Any patient whose tumor is large enough that they are not a good candidate for breast conserving treatment or lumpectomy should be considered for neoadjuvant therapy.
Some patients, particularly patients with hormone responsive HER2 negative breast cancers can achieve less radical or less deforming surgery by using neoadjuvant endocrine therapy, which in some cases and in some types of cancer, may be almost as effective as chemotherapy to convert them from a mastectomy to breast conservation.
Host: And this can also help with taking out lymph nodes that perhaps that will become less radical also?
Dr. Bear: Right, and that of course reduces the risk of lymphedema or arm swelling that may occur after removing all the lymph nodes. We do not remove all of the lymph nodes very often anymore. But for patients who start out with positive nodes, giving the neoadjuvant treatment may convert those lymph nodes to negative lymph nodes, which may in turn not only reduce the scope of the surgery but may reduce the need for regional radiotherapy as well.
Host: Now Dr. Bear, you’ve led many of the national clinical trials on these procedures and what is the research that is now going on to explore this possibility?
Dr. Bear: So, again, we have several trials ongoing to look at postsurgical treatments for the patients at highest risk who didn’t respond to chemotherapy and looking at immunotherapy. We are currently leading a phase 2 clinical trial testing the benefits of adding immunotherapy combinations to standard chemotherapy prior to surgery for breast cancer. One of the current trials was developed based on our own Massey laboratory research and it combines an immune therapy drug with what’s called a DNA methyl transferase inhibitor, which may make breast cancers more responsive to the immunotherapy.
There’s a tremendous amount of evidence that a brisk immune response in the tumor before the patient gets chemotherapy makes that tumor much more likely to have a good response to the neoadjuvant chemotherapy and for the patients to have a better outcome. So, the idea behind this trial is to improve the immune response in the tumor before we start the chemotherapy, and if that proves to be true, then it could very well increase the likelihood of a good response to the chemotherapy and give the patients a better chance for a better outcome.
Host: And you are still enrolling patients in this phase 2 trial?
Dr. Bear: Right. Absolutely. So, we still are looking to enroll about 30 to 40 more patients. We are about to add three other cancer centers around the country to the trial in the next month or so. But we are currently enrolling patients here, and again, we are looking for patients who have HER2 negative breast cancers. The reason for that is that the treatment of HER2 positive breast cancers is so successful in the preoperative setting that we do not think we need to use this approach yet. Therefore, either hormone responsive or HER2 negative or triple negative breast cancers, any patient who is being considered for neoadjuvant chemotherapy either because of the tumor size or the presence of lymph node spread or both would be potentially eligible for this trial.
Host: Finally, there has been research on combining immunotherapy and chemotherapy. Can you talk about that?
Dr. Bear: So, there was a trial that was reported at a meeting about two years ago where immunotherapy or what we call an immune checkpoint inhibitor was added to neoadjuvant chemotherapy and had showed a potential to dramatically increase the pathologic complete response rate. That is the percentage or proportion of patients in whom all the tumor had disappeared. There was a German trial, which was not quite as successful. The trial that was successful was a small sort of pilot trial. But what is really interesting is that some of the trials suggest that there is an interaction between chemotherapy and immunotherapy. Therefore, changing the immune microenvironment in the tumor can make the tumor more responsive to subsequent chemotherapy.
There is also data suggesting that chemotherapy, depending on which agents and how exactly they kill the cancer cells, may release tumor antigens in such a way that it stimulates the immune response and then combining that in the right sequence with immune therapy may also be beneficial.
Host: Dr. Harry Bear is the Chair of Surgical Oncology at VCU Massey Cancer Center. To learn more about breast cancer care at VCU Massey Cancer Center visit www.masseycancercenter.org. That is M-A-S-S-E-Y cancer center.org or call 877-4MASSEY. To listen to other podcasts from VCU Health, visit www.vcuhealth.org/podcasts. This is Healthy with VCU Health. I’m Alyne Ellis. Thanks for listening.
Alyne Ellis (Host): Breast cancer. Sometimes you can have a less radical surgery if you have chemo before the operation. Here to tell us about how this preop treatment works is Dr. Harry Bear, Chair of Surgical Oncology at VCU Massey Cancer Center. Welcome to Healthy with VCU Health. I’m Alyne Ellis. Dr. Bear, thanks for joining me. What is neoadjuvant therapy and how is it used to treat breast cancer?
Harry Bear, M.D., Ph.D. (Guest): So, the concept of using neoadjuvant therapy, which is giving a systemic therapy usually either chemotherapy or hormonal therapy prior to the surgical management of a breast cancer or any other cancer for that matter, really began in the 70s when we were confronted with patients who had cancers that were virtually inoperable. In other words, it wasn’t even possible to surgically remove the tumor with even a radical mastectomy.
Unfortunately, in those days, the drugs that we had available to us were not very effective, and so, even though it was the only option, it was not always terribly successful, but it could sometimes convert patients from being inoperable to operable. In the mid-80s, a number of researchers, including us at Massey, began exploring the approach of using this treatment in operable breast cancer patients – neoadjuvant therapy given before the surgery rather than after. And we learned that it was equally effective as giving the same drugs after surgery in terms of the patient’s overall survival. But it had a number of important advantages particularly for patients who would have otherwise required removal of the entire breast. Many of those patients could be converted to breast conservation surgery or a lumpectomy. In addition, more recently, we’ve learned that we can reduce the scope or the radicalness of the lymph node surgery in some patients who have positive nodes or may have positive nodes at the time they are diagnosed. We may not have to remove all their lymph nodes like we used to in the past.
Host: And if you do this treatment before surgery, does that open up other options after the surgery is over?
Dr. Bear: Well that’s really been the most recent benefit of the neoadjuvant approach. As we were investigating neoadjuvant therapy, we gathered convincing evidence that the response to treatment – in other words, how effectively the treatment shrank the tumor and sometimes to the point where there was no cancer left in the breast or in the lymph nodes at the time of surgery – was very predictive of how the patients were going to do long term.
So, patients whose cancers disappeared with the neoadjuvant treatment did very well, and patients who had even a little cancer left behind at the time of surgery had a much less good outcome and were much more likely to recur and die of their disease. And for a long time, there wasn’t a whole lot we could do about that. But more recently, particularly for triple negative breast cancers and for HER2 positive breast cancers, where we combine neoadjuvant chemotherapy with HER2 targeted therapy, we’ve discovered just in the last year or so, that giving certain additional treatments to patients with residual cancer has dramatically improved their prognosis and their likelihood of being cured.
So, now, this has become a valuable tool to assess whether the patient is very responsive to standard therapy and will do quite well or doesn’t respond so well to the standard-of-care therapy and needs something added. In some cases, the added therapy can improve their outlook. In addition, it provides a platform for doing clinical trials of new treatments where we try the new treatments on patients who have a very guarded or very grim prognosis and hopefully be able to improve that prognosis, such as adding immunotherapy for triple negative breast cancers that have an incomplete response to neoadjuvant chemotherapy.
Host: So, which breast cancer patients are eligible for neoadjuvant therapy?
Dr. Bear: Almost all patients with a HER2 positive breast cancer, unless it’s very, very tiny. Most patients or many patients with what we call triple negative breast cancer, that is breast cancer that does not respond to hormones and is not HER2 amplified or HER2 positive. Any patient with positive nodes should be considered for neoadjuvant therapy. Any patient whose tumor is large enough that they are not a good candidate for breast conserving treatment or lumpectomy should be considered for neoadjuvant therapy.
Some patients, particularly patients with hormone responsive HER2 negative breast cancers can achieve less radical or less deforming surgery by using neoadjuvant endocrine therapy, which in some cases and in some types of cancer, may be almost as effective as chemotherapy to convert them from a mastectomy to breast conservation.
Host: And this can also help with taking out lymph nodes that perhaps that will become less radical also?
Dr. Bear: Right, and that of course reduces the risk of lymphedema or arm swelling that may occur after removing all the lymph nodes. We do not remove all of the lymph nodes very often anymore. But for patients who start out with positive nodes, giving the neoadjuvant treatment may convert those lymph nodes to negative lymph nodes, which may in turn not only reduce the scope of the surgery but may reduce the need for regional radiotherapy as well.
Host: Now Dr. Bear, you’ve led many of the national clinical trials on these procedures and what is the research that is now going on to explore this possibility?
Dr. Bear: So, again, we have several trials ongoing to look at postsurgical treatments for the patients at highest risk who didn’t respond to chemotherapy and looking at immunotherapy. We are currently leading a phase 2 clinical trial testing the benefits of adding immunotherapy combinations to standard chemotherapy prior to surgery for breast cancer. One of the current trials was developed based on our own Massey laboratory research and it combines an immune therapy drug with what’s called a DNA methyl transferase inhibitor, which may make breast cancers more responsive to the immunotherapy.
There’s a tremendous amount of evidence that a brisk immune response in the tumor before the patient gets chemotherapy makes that tumor much more likely to have a good response to the neoadjuvant chemotherapy and for the patients to have a better outcome. So, the idea behind this trial is to improve the immune response in the tumor before we start the chemotherapy, and if that proves to be true, then it could very well increase the likelihood of a good response to the chemotherapy and give the patients a better chance for a better outcome.
Host: And you are still enrolling patients in this phase 2 trial?
Dr. Bear: Right. Absolutely. So, we still are looking to enroll about 30 to 40 more patients. We are about to add three other cancer centers around the country to the trial in the next month or so. But we are currently enrolling patients here, and again, we are looking for patients who have HER2 negative breast cancers. The reason for that is that the treatment of HER2 positive breast cancers is so successful in the preoperative setting that we do not think we need to use this approach yet. Therefore, either hormone responsive or HER2 negative or triple negative breast cancers, any patient who is being considered for neoadjuvant chemotherapy either because of the tumor size or the presence of lymph node spread or both would be potentially eligible for this trial.
Host: Finally, there has been research on combining immunotherapy and chemotherapy. Can you talk about that?
Dr. Bear: So, there was a trial that was reported at a meeting about two years ago where immunotherapy or what we call an immune checkpoint inhibitor was added to neoadjuvant chemotherapy and had showed a potential to dramatically increase the pathologic complete response rate. That is the percentage or proportion of patients in whom all the tumor had disappeared. There was a German trial, which was not quite as successful. The trial that was successful was a small sort of pilot trial. But what is really interesting is that some of the trials suggest that there is an interaction between chemotherapy and immunotherapy. Therefore, changing the immune microenvironment in the tumor can make the tumor more responsive to subsequent chemotherapy.
There is also data suggesting that chemotherapy, depending on which agents and how exactly they kill the cancer cells, may release tumor antigens in such a way that it stimulates the immune response and then combining that in the right sequence with immune therapy may also be beneficial.
Host: Dr. Harry Bear is the Chair of Surgical Oncology at VCU Massey Cancer Center. To learn more about breast cancer care at VCU Massey Cancer Center visit www.masseycancercenter.org. That is M-A-S-S-E-Y cancer center.org or call 877-4MASSEY. To listen to other podcasts from VCU Health, visit www.vcuhealth.org/podcasts. This is Healthy with VCU Health. I’m Alyne Ellis. Thanks for listening.