How to Treat Triple Negative Breast Cancer | Dr. Ruth O'Regan Chair & Dr. Anna Weiss

Welcome to Oncology Brothers: Triple Negative Breast Cancer Hello everyone, I am Rahul Hossein. Speaker 2 And I'm Rohit Hossein. Speaker 1 And we are oncology brothers. In 2023 we saw more than 40 new FDA drug approvals and indications for different diseases in oncology. As a general community medical oncologist, we need to be aware of all this data and how this fits in, in our day-to-day clinical practice. To make sense of all this that is available and to focus on current standard of care in triple negative breast cancer. We're joined by Doctor Ruth O Reagan, a breast medical oncologist and Dr. Anna Wise, a breast surgical oncologist from my home institution here at University of Rochester Beaumont Cancer Center. Ruth and Anna, thank you for joining us. Speaker 3 Thanks for having us. Thank. Speaker 4 You Anna. Speaker 2 Ruth, welcome. I feel outnumbered as I was saying before, part of Billmont cancer family for now. All right for today, Rahul. As Rahul stated, our focus is talking about triple negative breast cancer mainly focusing on standard of care for medical and surgical oncology standpoint. Approach to Early Stage Triple Negative Breast Cancer To get us started, Ruth, can you please walk us through your approach when it comes to early stage no negative, triple negative breast cancer? Speaker 3 Yeah, absolutely. So you know if the patients had surgery already which very often they have for you know, small triple negatives because you can accurately estimate the size always using radiology. Radiologic means I kind of look at the size of the cancer and then kind of decide how to treat patients. So for sure if the cancer is between 1 to 2cm, I would recommend chemotherapy to that patient and most likely as you can see here dose of taxol, cytoxan then radiation if appropriate and then surveillance after that. For T1A and T1B, again I look at the size, the age of the patient, any comorbid disease. But very often if they're larger T1B SI might consider for cycles of dose of tax or Cytoxan for those patients as well. But it's really a shared decision with with your patient and then standard local therapy after that. I don't typically treat T1A triple negative breast cancers, although I do think there in some cases that might be warranted as well. Speaker 4 Bruce, can I just add though, one of the things I hope to do today is to reinforce the use of neoadjuvant therapy and some of those even small triple negatives. You know, it might be 1 1/2 centimeters and a surgeon might say, oh, this is an easy lumpectomy, I can just do this. But you let the you lose the ability to assess that response like we'll talk about I'm sure in a second. So I really hope to kind of pound that boom today. Speaker 3 Yeah. And and I totally agree with that, Anna. And that's why I said if they've had surgery already when I see them because I I do agree with you, I think you know the larger T1 CS, we definitely would think about preoperative treatment, particularly in a younger patient. You know, I think one of the things there is you're kind of then have to think about agemymycin, Cytoxan followed by pack attacks on those patients because you don't know the exact stage, but absolutely agree with you. Speaker 1 Absolutely. And we'll see that the idea of neoadjuvant of course plays a bigger role with locally advanced or lymph node positive disease and you're brought up of the role here of neoadjuvant. But let's say surgery up front in a clinically node negative patient. In your practice, When it comes to node evaluation for this disease subset, what does that look like? Speaker 4 Yeah. So you know I fit these patients into Z11 criteria, so I would do the Sentinel node biopsy and and you know continue them along even with one or two positive nodes they would not need an extra dissection. So pretty standard at this point. I think most people accept that for all some types. Speaker 2 Thanks. Now going back to Ruth, from chemotherapy standpoint, now when do you usually utilize TC versus ACT when talking about less than two centimetre and what is a clinical scenario if one gets chemotherapy less than one centimetre? Do you utilize chemotherapy in the patient population? Speaker 3 So, so I think I've just to reword your your your question. So dealing with the the T1 BS first I think you know first of all I I wouldn't give them more than dose of taxol Cytoxan and and I think again you know it depends on the size of the cancer you know the age of the patient any comorbidities there are the kind of things I would take into account. Also keeping in mind that you know triple negative is very heterogeneous and there is that low grade type that you sometimes see which very often is apocrine features. And I I've I'm much, I'm much less likely to recommend chemotherapy to those patients than I would with somebody with more classical classical triple negative breast cancers. And I think the second part was for T1 CS how do you decide between ACT versus TC. The data from the ABC trials suggests that in those patients with no negative smaller triple negatives that they're fairly equivalent, although there were nuances with that trial because those trials because they do deduce more than four cycles of TC. So I I generally unless it's a very young patient I probably would just go with TC up to two centimetres. But I think there are selective patients where I might use an anthracycline, you know we have as I'm sure you may would do as well, we have a Co cap machine. So we know that the Co caps work well with TC, but they don't really work very well once you start adding an anthracycline and that's something to take into account as well I think. Speaker 1 Absolutely. And even just at San Antonio, breast cancer 2023, we saw some debate about when to use antracycline. Immunotherapy in High-Risk Triple Negative Breast Cancer Ruth, thank you for covering the early part, but moving on to high risk or locally advanced. And since July 2021, based off keynote 522 immunotherapy has been part of the standard of care here. Can you please walk us through your treatment algorithm in this patient population? Speaker 3 Yes. So for patients whose cancers that are greater than or equal to two centimetres in size and are node positive, your options really are ACAC followed by pactataxal or more and more increasing as you mentioned the keynote regimen which is you know AC Carboplatin, pactataxal with the addition of pembrolizumab. In terms of deciding about that again you know I think taking in obviously patients with no part of disease, I would absolutely consider pempronizumab larger cancers. I would certainly consider pempronizumab. Obviously it's a tougher treatment and you can put patients at risk of longer term immune related toxicities. So you know taking into account again the patients age comorbidities I think would be important here. But we do know that the pathologic complete response rate is higher. If you add in the immune therapy and the long term outcome, it's also improved. So that's kind of what I would do. Then they go to surgery, you make your decision based on what kind of response they had to that treatment. So it could be surveillance if they'd had pembrolizumab. Right now the standard of care is continue for approximate a total of approximately a year. If they have a residual disease, keep Cidabine for 8 cycles based on create X and then if they've got a BRCA one or two germline mutation using a PARP inhibitor, clearly we have data support doing that as well. Speaker 2 Thanks Ruth. Though we did see an update on San Antonio Breast Cancer Symposium 2023 that EFS benefit has been sustained and particularly in T2N0 subset and node positive disease. So important to stress that and utilize immunotherapy as much as we can in neoadjuvant setting and coming to your point on multi disciplinary approach, it is very critical to decide whether upfront surgery is beneficial versus neoadjuvant treatment particularly here in this disease especially now with the EFS benefit. Any particular thoughts from what you were iterating before to community oncology here? Speaker 4 Yeah, absolutely. I mean I think that the real like I said from my standpoint the real take away is that these patients should all have neoadjuvant therapy you know greater than 2cm. I think it's almost malpractice at this point to not be giving you adjuvant therapy. I mean that's a bold statement but you know but I I really do believe in it and I think you know we get the chance to escalate the therapies like we've talked about and I think from a surgery standpoint we should not be worried about the axilla much anymore. You know we're seeing these higher PCR rates. So I, you know we're going to clear the axillary nodal disease most likely you know and in terms of axillary management, I think the most important take away is that if there's residual disease it really should be still doing an axillary dissection. But I will say if you're supported by a multidisciplinary you know, case conference, you can, I would say we're getting to a point discuss you know the volume of that residual disease and it's if someone was CN zero and has a really small volume or CN one really small volume. You know some are considering omission of Axler dissection per St. gallon especially. You know those experts have kind of said we may not need need to do these Axler dissections even though we don't have data for this yet. But I would say if you do not have the support of a multidisciplinary group, then you know you should do a dissection for residual nodal disease. Speaker 3 I was just going to say one other thing here. You know, I, and I don't know if this there's really no Jay support doing this, but you know, you know, the keynote regimen can be fairly toxic as we know, and most of us start with pack of taxol carbon permboilizumab. I will image them after the 12 weeks of treatment and if they've had a complete response in certain patients, I might talk to Anna and say maybe we could do surgery and then decide whether they really need the anthrocycline on the back end. But there's nothing to support doing that. But I think that prispat CR is such an important prognostic factor, I think it's a way of potentially de escalating treatment as well. Speaker 4 So the conversation is so important because if I'm still worried about their axolot or something like that, you know then we will. We won't do that. We'll just continue because we want to make sure we're utilizing the neoadjubant therapy, you know, leveraging it to to, you know, minimize surgery to kind of a balance there. Speaker 3 Yeah, absolutely. I, I and I would never do without talking from my surgical colleagues. Speaker 1 And you know in our field we've historically over treated. So now is the time to start doing this to de escalate treatment. While we're talking about residual disease, Ruth, let me push you a little more on this idea. Patient got Keno 522 upfront. There is residual disease. Are you going to continue pembro and add Cape Cytabine if to have germline mutation? Are you going to add PARP in the bitter? Speaker 3 I will usually continue the pembrolism because we we don't have data to stop it at at this point. There's plenty of safety data with kepsitabine and pembrolismab and with the PARP inhibitors and pembrolism app. So I'm pretty comfortable doing that. I think if they have a germline mutation though, I would pick a PARP inhibitor over kepsitabine in that in that setting because I think the data is a little bit more convincing. Speaker 1 Absolutely. Speaker 2 And just to go back on your point, Ruth, when a person who did have this limited therapy without anthracycline base and the patient did have complete response at least on radiological imaging say PET CT after surgery, there is residual disease was found. In that case, are you planning to just continue on with pembrolizumab and add capacitamine because there was residual disease present at that time? Speaker 3 I think it's a discussion but but I think that if they haven't had an anthrocycline, you know I I think depending on the amount of physical disease I would talk to them about doing the AC at that time point that's that's a real problem. That's why you have to, I think be very careful in in that scenario because you know I I think as Rahul said we we certainly don't want to over treat, but we also don't want to under treat and. Speaker 1 They all right. Algorithm for Metastatic Triple Negative Breast Cancer Now switching gears to metastatic disease, not long ago we had very limited treatment options here, but now we have immunotherapy and antibody drug conjugates along with chemotherapy. Ruth, back at you. Can you share your treatment algorithm for metastatic disease? Speaker 3 Yeah, absolutely. And of course, you know some of what we do is a little bit dependent on how, how when the patient relapsed after adjuvant treatment. But obviously we'll check PDL one status if it's positive, I would treat with pembrelizumab plus chemotherapy. The nice thing from the KEYNOTE study is that you know if they've had a prior taxane, you can use gem carbo as your chemotherapy backbone. If they're far out from a taxane, you know we can use either a packed attack cell or nab packed attack cell. If they're PDL one negative, then I guess obviously looking at to see if they've got a BRCA mutation would make sense. The data from the with with the PARP inhibitors do suggest that if if you give them the first line setting, they actually have more of an impact on survival. So I think doing that with the lap rib in particular I think would be very reasonable here. If they don't it's kind of chemo of our choice. I think all the chemotherapy single agents are pretty much very similar in terms of response in in that first line setting and then a progression. I think as you've outlined here looking at her two status to see if they've got some low her two expression in which case using transducer map, deroxetecan would certainly be an option. And then Saji Tusa map and there's very strong data with Saji Tusa map as well in and that's effective in both the her two low and the her 20 setting. So it's very exciting because we now have these AD CS that we didn't have before and the question will be, of course, can we use them earlier. There's ongoing trials with statutuzumab in the first line setting, both with Pembrolismab and without Pembrolismab. So we'll await the results from those. Speaker 2 Exactly. These are exciting times indeed. But it is important to keep the indication of utilization of these medications in mind that pembrolizumab in locally advanced setting is approved for all comers. When Ruth was stressing PDL 1 positive that is pertinent to CPS score of more than or equal to 10. Role of Surgery for Oligo-Metastatic Disease And that's when we can utilize in metastatic settings, Anna, any role of surgery or local regional for mainly for local regional control in metastatic setting, especially when we're talking about oligo metastatic disease, because that question comes a lot especially in community cycle. Speaker 4 Yeah, I would say rarely, but yes, you know, so our clinical trials around this have shown no survival benefit. And then of course as surgeons, we hope that our surgeries would make people feel better, but they actually also showed no quality of life improvement either, if anything a little bit worse. So I really reserved surgery for the patients that have symptoms, maybe they're having breast pain, maybe they have some breast lymphedema, you know, remaining even though they've had a good response, Is it close to the skin And with are we worried later when they stop responding there's going to be a wound because it's really superficial. You know those are the really the patients that I reserve surgery for in this setting. It's very tempting in all of the metastatic disease to to do a surgery, but it's there's just not a really big indication for it. I. Speaker 1 Know, thank you for covering that. Especially in metastatic settings, it's so important to keep these two things in mind. Is it going to affect your overall survival? Is it helping your symptoms or quality of life? Managing Toxicities of Antibody Drug Conjugates As we're nearing the end, I want to take a few minutes to talk about supportive care and toxicity management, especially when we're talking about antibody drug conjugates. With TDXD, we worry about fatigue, nausea, hair loss and pneumonitis, whereas when it comes to sassitismab, we worry about neutropenia and diarrhoea. Any clinical pros to manage these toxicities with these new AD CS? Speaker 3 I I think just being very proactive on them. I mean they are, they do have some toxicity, there's no question about it and I think it's always a very unfortunate when you cause MOP shared to patients with metastatic disease. But given how effective they are, you know I think most patients are probably OK with that. You know, I think diarrhoea we've lost antidiarrhoea has been very proactive with that I think makes sense, you know being very careful with the TDXD to to basically look for any pneumonitis because obviously that's a very serious side effect for patients. Speaker 1 Yeah. So as community oncologists, we get to use Sassy to zimab and bladder cancer. You brought up a trial for Sassy and that's happening in lung cancer as well. And TDXT is now approved almost in every disease site and the idea of pneumonitis is important because there were deaths related to this. So we have to keep that in mind and stopping and using steroids in that case is very important. And sassitism that we know we have overall survival benefit here, but managing that neutropenia and diarrhea is critical. So we thank you for going over that. Speaker 2 Right. We are used to seeing pneumonitis especially with immunotherapy. But again, the TDXD immunother pneumonitis is extremely concerning as Raul mentioned, mortality association with it, which is certainly very concerning. So one has to be very, very diligent with acting on it. Key Takeaways for Triple Negative Breast Cancer Well, we've covered a lot here, Ruth and Anna, thank you so much for joining us and reiterating the current standard of care for triple negative breast cancer today for our listeners. Stay tuned for a short recap. In this discussion with Doctor Ruth Oregon and Anna Weiss from Wilma Cancer Center, we cover the current standard of care for triple negative breast cancer. The importance of a multidisciplinary approach in this disease cannot be stressed enough when looking at early and locally advanced disease. We have discussed the role of immunotherapy in neoadjuvant and adjuvant settings. Speaker 1 When focusing on metastatic disease, immunotherapy plays a role here as well, but with CPS of 10 and above, then we've also discussed role of TDXT, insassitizumab and chemotherapy in this space. Speaker 2 The jury is yet to be out on what exactly is the current sequence for these antibody drug conjugates, but we fortunately have these treatment options available for our patients today. Make sure to check out our R2 positive and hormone receptor positive discussions as well. We are the oncology brothers.