Amanda Wilde (Host): Recent developments have shaped and deepened our understanding of HER2 breast cancer. In this breast cancer update, we'll cover the new category of HER2 low breast cancer and new treatment options with Dr. Jamie McKenzie, senior Breast Medical Oncologist, TGH Cancer Institute. Welcome to MD Cast by Tampa General Hospital, a go-to listening location for specialized physician to physician content, and a valuable learning tool for world class healthcare. I'm Amanda Wilde. Dr. McKenzie, thank you for being here.

Dr Jamie McKenzie: Thank you Amanda. I'm very excited to be here to talk about some of the updates in breast cancer, management in 2023.

Amanda Wilde (Host): Well, how is this new category, HER2 low breast cancer discovered, and what defines that?

Dr Jamie McKenzie: So if I can back up, just a second. I can let you know where this HEr2 designation came from originally and Tell you about the recent changes. So what HER2 is, is it's a protein on the surface of breast cancer cells that helps to control the cell growth and division. We previously, defined the HER2 status of a breast cancer using a binary fashion. So, Breast cancer was either HER2 positive or HER2 negative. HER2 positive means that there was a high level of this,HER2 protein being expressed on the surface of the cells using, something called immunohistochemistry or gene amplification.

So the old definition of HER2 positive was you had something called three plus on immunohistochemistry or two plus with a subsequent test that was positive called inside HER2 hybridization. HER2 negative is the remainder of those patients. That means you're, classified as HER2 zero or one plus on immunohistochemistry or two plus, with a subsequent test, the inside HER2 hybridization being negative. That alone was pretty remarkable in the breast cancer world finding, this HER2 protein and targeted therapies, which people are probably familiar with, the earliest was called Trastuzumab or Herceptin, led to a pretty dramatic improvement in the survival of HER2 positive breast cancer patients.

So to tell you kind of what the recent evolution has been, this third category of HER2 low, includes some of those patients that were originally HER2 negative. That includes those patients that have an immunohistochemistry of one plus or two plus with the negative subsequent inside two hybridization test.

Amanda Wilde (Host): And how common is this HER2 low disease?

Dr Jamie McKenzie: It is surprisingly common. So if you look again at the prior definitions, HER2 positive patients make up about 15 to 20% of all metastatic breast cancer patients. HER2 negative was 80%. So the vast majority of patients are HER2 negative. if you include now this HER2 group. Basically the HER2 positive group stays the same. That's 15 to 20%. The HER2 low negative group goes down quite a bit to 30 to 40%. And this HER2 low group is actually about half 45 to 55% of all breast cancer patients fit this HER2 low category.

Amanda Wilde (Host): Well that's a highly significant number are there now targeted treatments for how you can treat HER2 low breast cancer?

Dr Jamie McKenzie: Absolutely. So the next question is, why did we come up with this group and does it really matter? And yes, this is a targetable group of patients that all the 50% of women now that are in this HER2 low group have had a significant advancement in their treatment options. And that includes, a specific drug that is within also a new category of drugs for breast cancer called antibody drug conjugate.

Amanda Wilde (Host): And what are those?

Dr Jamie McKenzie: So I think most people know kind of the treatment of cancer in general has always relied on, chemotherapy, right? These drugs that are given, and get into the bloodstream and just are targeting cancer cells somewhat indiscriminately, and having side effects because it's also affecting normal cells. So this new group, these antibody drug conjugates, basically are linking a chemotherapy drug. To, an antibody that's specific to, something on the surface of a cancer cell. So it's basically allowing for, that chemo that's linked to the antibody to be delivered directly to the cancer cell rather than just indiscriminately like the old way with chemotherapy. It basically is enabling tumor specific targeting, which is pretty exciting.

Amanda Wilde (Host): Yes, but do you have the same side effects as you would have with traditional chemotherapy?

Dr Jamie McKenzie: Some are similar, because again, at the end of the day, the chemo drug does get broken off from the molecule. and in some research studies that we can talk about, they did see similar rates of the traditional side effects. Things like low blood counts, fatigue. But I think in general those tend to be much milder than for patients that are on standard chemotherapy drugs. So this antibody drug conjugate group, it includes, probably at least a half a dozen drugs now that are being used in cancer. The drug that was found to be effective for this large group of women, this HER2 low group is a medicine called Trastuzumab. Duruxucan or, and HER2 is the brand name.

And the way this medicine works is, the, antibody is basically the same hertu protein on those, cancer cells. And it's linked to a chemo drug called Deruxucan, which is related to some other, standard chemotherapy drugs. This has made a remarkable improvement in not just this, HER2 low group. It started being studied in the HER2 positive group of patients. So, we've been using, this n HER2 therapy for HER2 positive patients since 2019. So that's actually been about three years we've been using it in that group.

And then now with the HER2 low designation, it was approved, in April of 2022. So we've been using it in this HER2 low group for just under a year, compared to chemotherapy. In this HER2 low group, it has, really advanced, how long women are living before they're needing their next treatment, as well as how long they're living, across the board. So we're, quite excited about using this, not just now in HER2 positive, but also HER2 low patients.

Amanda Wilde (Host): So you're seeing an improvement in survival rates and in cancer-free living. As we wrap up here, what is your perspective on future directions for these new drugs in the diagnosis and treatment of HER2 low breast cancer?

Dr Jamie McKenzie: So I think the next question that the researchers are trying to figure out is basically how low is, too low to benefit? There was a smaller study looking at women even in that HER2 negative group, the IHC zero, and they've seen benefit of using this in HER2 medication, even in that group. So now they're. Conducting a, bigger randomized trial, that's including not just the new HER2 low, they're now even thinking of this HER2 ultra low category. So I think some of us, as breast oncologists are wondering is, there gonna be a patient across the board that's not gonna benefit?

That remains to be seen, but it's pretty exciting. They're using these drugs now in combination with other, more traditional, cancer directed therapies like chemotherapy, immunotherapy, endocrine therapy to see if we can improve the outcomes even more. There's also a second antibody drug conjugate that we are using in a different patient population in breast cancer called Sasatuzamab or Trudelvy. That drug has been around about two years now in the triple negative breast cancer patients. and it just got approved earlier this month, February, 2023, for HER2 positive breast cancer patients.

So I think the whole world of breast cancer is really moving away from chemotherapy. It doesn't work all that well. It has these nasty side effects to these more targeted, therapies. And there's several. Antibody drug conjugates that are in research that I think we will have at our disposal in the next couple of years.

Amanda Wilde (Host): Well, it sounds like the more targeted treatments are also more individualized and have really. Added to survival rate and quality of life.

Dr Jamie McKenzie: Absolutely. I think we still have a ways to go with targeted therapy, truly, but, it certainly is a big difference compared to 20 years ago.

Amanda Wilde (Host): Dr. McKenzie, thank you so much for your time and your insights, and we'll join you for the next update.

Dr Jamie McKenzie: Thank you Amanda.

Amanda Wilde (Host): Thank you for listening to MD Cast by Tampa General Hospital, which is available on all major streaming services for free. To collect your cme, please click on the link in the description. For other CME opportunities, including live webinars, on demand videos, and local events offered to you by Tampa General Hospital, please visit cme.tgh.org. Thank you.