The text transcription has been edited for length and clarity.
Parvin Peddi, MD (PD): Hello! My name is Dr Parvin Peddi and I am a Breast Medical Oncologist. I am the director of Breast Medical Oncology at the Margie Petersen Breast Center at Providence Saint John’s Cancer Institute, Santa Monica, CA.
Macy Duong, MSN, APRN, FNP-BC (MD): Hello! My name is Macy. I am a board-certified nurse practitioner currently working at Providence Saint John’s Cancer Institute in the field of breast medical oncology.
Navigating Initial Conversations About HER2-Positive Breast Cancer Therapy
PD: When I meet a patient with HER2 (human epidermal growth factor receptor 2)-positive breast cancer, first of all I tell them how far the treatment of HER2-positive breast cancer has come. I tell them that we did not know about this type of breast cancer before the 1980s. When it was first discovered, we realized it was a more aggressive type of breast cancer and people did poorly. Then, I quickly tell them that things have changed a lot and with the advent of trastuzumab, then pertuzumab, and the many other targeted agents since then. No other field of breast cancer has seen as much advancement as the HER2-positive breast cancer patients.
I tell them that now HER2-positive breast cancer has changed from being a worse type of breast cancer to actually being a better type of breast cancer because the treatment is so good. I put that in perspective and that is usually my discussion with patients for HER2-positive. I want my patients to understand that yes, it is more aggressive but if you treat it right, they actually fare better than those with other types of breast cancer. That is to say, patients with HER2-positive disease need to take their diagnosis seriously but at the same time be very, very optimistic.
Effective Conversations About Side-Effect Management: Key Components
MD: With anti-HER2 therapies it may cause some cardiac problems, including a reduced heart ejection that can result in congestive heart failure so it is an important part of the discussion to educate patients to watch out for any symptoms that they might have including swelling of the legs, shortness of breath, cough, or even waking.
Before starting therapy, port placement for central intravenous access is needed as well as obtaining an echocardiogram to assess the patient’s baseline heart functioning. It is essential to continue cardiac monitoring throughout the duration of therapy to evaluate if there is a decline in their left ventricular ejection fraction as well as to avoid any potential treatment-related cardiotoxicities.
Approach to Discussing Goals of HER2-Positive Breast Cancer Therapy
PD: The goals of therapy are no different than other types of breast cancer so typically if a patient comes in with stage I, II or III breast cancer you talk to them that the goal is cure. The goal is to completely get rid of this cancer. Obviously, someone who has stage III breast cancer may need more treatments to get them there and they have a little bit higher risk of not being successful in that endeavor but still that is a goal. The goal is to cure.
Someone comes in with metastatic breast cancer whether they are HER2-positive or not, unfortunately, for most patients I tell them that goal is not cure. The goal is prolonging life, improving quality of life, and putting in some kind of remission. There are some patients with HER2-positive metastatic breast cancer that are doing great years and years down the line.
Is it potentially possible to cure some patients? It is unclear and maybe it can be, but I do not think that is a realistic goal to tell the patients about. I tell them that I am hoping for a long remission and hopefully for less than symptoms and you are doing better in terms of your quality of life. In general, cure for met and localized disease versus maintaining and prolonging life for someone who has metastatic disease.
Optimizing Factors Related to Adherence to the Recommended Duration of Therapy
MD: Most patients are able to tolerate targeted anti-HER2 therapy with trastuzumab and/or pertuzumab that generally lasts for one year in duration. It is usually used as part of the treatment regimen with other chemotherapy drugs so to manage the common side effects like diarrhea with pertuzumab, we would initiate prescribing antidiarrheals as well as intravenous fluids as part of the regimen to replace any dehydration losses that they might have, and also just getting the patient ready mentally before treatment is also important in improving patient adherence.
PP: Patients just need to understand that anti-HER2 therapy whether it is in the localized setting or whether it is in the metastatic setting is typically of a longer duration than treatment for other types of breast cancer. Even when you drop the chemotherapy, you need to continue the anti-HER2 therapy for much longer. Stress to them that it is temporary, a lot of the side effects go away when you are on just an anti-HER2 part, and that helps as well just for them to mentally know that yes, I still have to come every 2 weeks but at least most of my side effects are gone. Exactly.
Discussions Regarding Modes of Administration for Systemic Therapy
PP: A subcutaneous (subq) formulation of trastuzumab is now FDA (US Food and Drug Administration)-approved and appears to have the same efficacy and bioavailability as the IV (intravenous) formulation.
However, for a lot of patients because trastuzumab is not the only medication, they still have to get chemotherapy as well. They already have a port in place for the chemotherapy portion and they do not mind coming in and just using the port for the IV administration of the targeted therapy. The subq injection can sometimes cause discomfort where the site of injection is and it depends on the patient’s preference. If someone already has a port and they are happy to use their port and there is no issue, then I will continue using the IV version of trastuzumab. If they do not have a port, they have lost the port for some reason or they have poor IV access, continuing with the subq formulation to deliver trastuzumab is a very good option for them.
Those would be the different scenarios when I would discuss different formulations of trastuzumab with patients.
MD: My experience has been mainly with the IV route for many of the anti-HER2 systemic therapies. Usually, every 3 weeks for the total duration of a 1 with each infusion ranging from 30 to 90 minutes.
As Dr Peddi mentioned, since a lot of these patients already have a chemotherapy port in place, they may not mind coming in for an IV infusion of anti-HER2 therapy. It becomes part of their routine to come in every three weeks to just get the infusion. Then there are some current studies that were performed comparing the 2 routes of administration which showed that the subq injection route has more site related events such as experiencing some pain or erythema to the site so that is mainly what I have been hearing with the two routes.
Emerging Treatments for HER2-Low Breast Cancer
PP: I think it is been like what I said before, it has been very exciting [in] HER2-positive breast cancer arena. We had the first smart chemo drug in breast cancer or any solid cancer approved in the HER2 area with ado-trastuzumab emtansine and T-DM1 (trastuzumab emtansine). Since then, we have trastuzumab deruxtecan, which seems to be even more efficacious for T-DM1 for the treatment of these patients, which is a smart chemotherapy that targets the HER2-positive cells.
Now only recently, we have approval for treatment of that same compound that smart chemo trastuzumab/deruxtecan that was approved in August 2022, just this month, for the treatment of so-called HER2 low patients now. Meaning they have some HER2 expression, but not quite enough to reach the cutoff level for what has been defined as HER2-positive, but they are not completely HER2-negative either. Up to 50% of breast cancer patients would fall into this category, which is a large number of patients. Now this drug which is an anti-HER2 drug is approved for them as well when the patients need IV chemotherapy and they have already tried at least one round of chemotherapy, it is better than other types of chemotherapy.
The area of HER2-positive breast cancer has seen so much advancement that use of current targeted treatments are basically making their ways to other types of breast cancer which is amazing because those drugs have been proven to be very effective with so little, relatively speaking, side effects.
Ongoing Clinical Trials in HER2-Positive Breast Cancer
PP: Yes, I think there are lots of ongoing clinical trials in HER2-positive breast cancer. We are opening up clinical trials right now in our center and many other places around the country to try to figure out how to improve upon the treatment of HER2-positive breast cancers, including when to add a HER2-targeted drug for people who do not have advanced cancer. Oral medications like tucatinib or neratinib added to your traditional IV, anti-HER2 drug in the nonmetastatic setting. That’s one area.
Then in the metastatic setting, how to prolong the time that you just prolong the time that you are just on anti-HER2 therapy and not needing any additional chemotherapy. Whether it is addition of oral drugs, whether addition of immunotherapy, those are all being explored right now. It is a very exciting time to see all the advances in HER2-positive breast cancer treatment.
The last area that we need to improve upon is treatment of the CNS (central nervous system) with HER2-positive breast cancer goes to the CNS. This is a challenge because many currently available anti-HER2 drugs do not penetrate the blood-brain barrier. That is an area of active research because our treatments are so good that the rest of the body is quiet for a long, long time and you are now seeing late occurrence of the tumor finding its way to the only place it can grow, which is the CNS. We are working on that. Improving on figuring out smaller agents that can cross the blood-brain barrier and get to the CNS. More to come, but it has seen a lot in this HER2-positive breast cancer field and it is been great to watch our patients have improved survival rates year after year with newer and newer drugs.
Additional Clinical Considerations for Anti-HER2 Neoadjuvant Therapy
PP: One thing is that a lot of times when we administer chemotherapy combined with anti-HER2 therapy in the neoadjuvant setting especially when it is a 4-drug combo like trastuzumab/pertuzumab/docetaxel and Taxotere, treatment can be rough for the patients in terms of side effects, diarrhea, dehydration. Even though it’s not part of the treatment guidelines, I typically add prophylactic IV fluids for a few days after each chemotherapy session for these patients and then add more fluids in the 2 subsequent weeks as needed. That I have seen help a lot in these patients being able to better tolerate these medications.
That and also just being mindful of the fact that neoadjuvant treatment is the best method. This is the best way of treating these patients when they present with localized disease rather than after surgery in the adjuvant setting, because now, we have the approval for T-DM1 and perhaps in the future trastuzumab deruxtecan, so those are medications that you would lose access to and you would not know which patients need it if you gave patients chemo only after surgery. Even if it is operable, that is not the point, and I would give almost all of these patients neoadjuvant chemotherapy unless they are super-small- like less than 1 cm.
That would be another thing to keep in mind and to talk with your surgeons so they are aware that it would be preferable to give chemotherapy beforehand.MD: Mainly, I counsel patients on the side effects that they should expect, especially diarrhea, since that side effect is a really prominent one with pertuzumab. A lot of the patients become routine; we get to know our patients a little bit more especially when we see them a lot more throughout the week for scheduled administration of the IV fluids. Overall, just allowing the patients to really just know what therapies they are getting, understanding and educating them what types of chemotherapy they are getting, also what the difference in the available anti-HER2 therapies and how they are different is really important in the discussion.
Parvin Peddi, MD, reported affiliations with AstraZeneca Pharmaceuticals, LP; Eli Lilly and Company; Gilead Sciences, Inc.; Laekna Therapeutics; Novartis Pharmaceuticals Corporation; and Sanofi-Aventis U.S. LLC.
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Reviewed September 2022