Let us talk about integrating ADCs into HER2-negative, ultralow, and low metastatic breast cancer treatment algorithms. And we will start with a patient case.

[00:03:40]

Patient Case 1: Patient With HR+/HER2-Ultralow Unresectable Breast Cancer

This is a patient with hormone receptor-positive, HER2-ultralow, unresectable breast cancer. She is 54, she is a math teacher. She has a history of ER-positive 85%, PR-positive 20%, and HER2 IHC 0 stage IV breast cancer. She is initially prescribed endocrine therapy and a CDK4/6 inhibitor as a standard of care.

At a 6-month follow-up visit, the patient reports new vision disturbances, dizziness, and disorientation. And so, an MRI brain is performed, which confirms multiple CNS lesions, one 2 cm parietal and one 1 cm temporal lobe lesion. You get scans of the body as well, which show innumerable liver lesions, and a bone scan shows new bone metastases.

A biopsy of the liver now is read as ER 30%, HER2 IHC 0+, or basically ultralow by IHC with some staining, as is shown here.

[00:04:37]

Pretest 2: In your current practice, which of the following options would you recommend for this patient?

In your current practice, which of the following options would you recommend for this patient?

1. Eribulin;
2. Single-agent chemotherapy;
3. Sacituzumab govitecan; or
4. T-DXd.

Please vote.

Speaker: Poll is open. Five more seconds. All right, thank you. We will close the poll and share the results.

Dr. Huppert: Great, so some mixed answers here actually. The highest votes for T-DXd at 38%, but many choosing single-agent chemotherapy, eribulin or SG, actually. So let us talk this through.

[00:05:37]

Patient Case 2: Patient With TNBC

This is a second case, though, first. This is a 42-year-old female with breast cancer diagnosed in 2023, is de novo disease with two 2 cm liver metastases at diagnosis.

Biopsy reveals ER-negative, PR-negative, HER2-negative, IHC 0, with a PD-L1 of 15% (positive). She is treated with first-line nab-paclitaxel and pembrolizumab for the KEYNOTE-355 trial. But unfortunately, 1 month into treatment, she also has headaches, which prompt imaging, and is found to have a solitary 1.4 cm brain metastasis. She undergoes SRS for this and remains on nab-paclitaxel and pembro for 9 months, after which she progresses in the nodes and now has a new 1.2 cm liver met with a stable brain MRI.

[00:06:24]

Poll 2: In your current practice, which of the following treatment approaches would you recommend?

In your current practice, what would you recommend for this patient? So this is basically looking at into the second-line triple-negative breast cancer with brain mets and liver mets.

1. Single-agent chemotherapy;
2. Dato-DXd;
3. Sacituzumab govitecan;
4. T-DXd.

Please vote.

Speaker: Poll is open. Five more seconds. All right, thank you. We will close the poll and share the results.

Dr. Huppert: Great, so also some mixed responses here. Lots of votes for T-DXd. Also, a quarter voting for Dato-DXd, 21% saci, 17% single-agent chemo. Excellent.

[00:07:21]

Overview of HER2 in Breast Cancer

Let us talk about HER2 evaluation in breast cancer.

About 15% of breast cancers are considered to be HER2-positive as defined by the ASCO CAP guidelines. This is IHC 3+ or 2+ and ISH-positive. And this is linked to a more aggressive phenotype and is a validated therapeutic target. So you can either be HR-positive, HER2‑positive or [inaudible 00.07.45 – 00.07.48] in total.

[00:07:50]

Previous Binary Classification of HER2 in Breast Cancer

And previously we really only cared if patients were HER2-positive or -negative. And we did not pay as much attention to whether they were HER2 IHC 0, 1+, 2+, etc., if their ISH was negative. So what we have learned, though, is that there are abilities to utilize some of these ADCs with lower levels of HER2 expression.

Specifically, a patient who is 2+ ISH-negative, 1+, or even between 0 and 1+ which is termed ultralow. So it is called HER2-low if it is 1+, 2+ ISH-negative. And then ultralow is basically a faint amount of membrane staining, less than 10%, but not just null. So between 0 and 1+, that is called ultralow. And we can now utilize T-DXd in these patients based on data from DESTINY-Breast04 and DESTINY-Breast06. It is more important to sort of pay attention to this level of detail.

[00:08:42]

ADCs in HER2-Low/Ultralow/Negative mBC

We now have 3 ADCs that are approved in HER2-low, ultralow and negative metastatic breast cancer. T-DXd is approved in HER2-low and now ultralow in the HR-positive cohort. This is a HER2-directed ADC that has a DXd payload, has great CNS penetration, a highly effective agent across all 3 subtypes.

Sacituzumab govitecan is a TROP2-directed ADC that has an SN38 payload. Also a topoisomerase 1 inhibitor payload, more potent than the parent compound of irinotecan. You do not need to check the TROP2 level of expressions. There is no specific biomarker. This is now approved in both HR-positive/HER2-negative breast cancer, as well as triple-negative breast cancer.

And then Dato-DXd is our newest kid on the block here, also a TROP2-directed ADC, but then it has the same DXd payload as T-DXd. I think of it as a hybrid, if you will, between SG and T‑DXd with the same target as SG, the same payload as T-DXd with the DXd payload. This also has no biomarker. We do not need to check TROP2 levels. It is now approved in hormone receptor-positive/HER2-negative metastatic breast cancer. And recently we have seen data in triple-negative, although not yet approved in that setting, but likely will be soon.

[00:10:08]

T-DXd: Efficacy and FDA-Approved Indications in HER2-Low/Ultralow Breast Cancer

And so, this is a summary of some of this data.

I mentioned that T-DXd is approved in HER2-low and ultralow breast cancer based on 2 trials that are really important, DESTINY-Breast04 and DESTINY-Breast06. And so, DESTINY-Breast04 was the first trial that we saw data from, and this specifically looked at T-DXd in the HER2-low population. So IHC 1+ or 2+ ISH-negative. These patients had to have 1 to 2 prior lines of chemotherapy, and then had to already be treated with endocrine therapy and thought to be endocrine therapy resistant.

This data showed that patients with on T-DXd outperformed the chemo arm, 9.9 vs 5.1 months overall. Most of the patients in this trial were HR-positive. There were about 60 triple-negative patients. So that is why this is in the all patients on the left. And then, specifically, just looking at those HR-positive patients, taking out those 60 triple negatives, the data was very similar, 10.1 vs 5.4, hazard ratios of about 0.5 in each.

We have also seen an improvement in median overall survival in all patients, 23.4 vs 16.8, as well as in the HR-positive cohort, as shown. And so, this received full FDA approval in August of 2022, and is now the standard of care in this population.

More recently, we saw data from DESTINY-Breast06, which asked several different questions. It said, number 1, what about the ultralow group? Can we use T-DXd in patients between 0 and 1+? And then it also asked, should we be using this in the first-line chemo setting? And so this was patients who had been on endocrine therapy, but no prior chemotherapy. And what we saw is that T-DXd outperformed the chemo arm here as well.

In the ITT population, 13.2 vs 8.1, a hazard ratio of 0.64. And then splitting out the HER2‑low and ultralow, you can see the numbers look very similar in both of those groups, which was very reassuring. I think I feel very comfortable using T-DXd across the board in the HER2-low and ultralow based on these data. The median overall survival, not yet reached in any of this trial yet, but was FDA approved actually about a year ago now, in January 2025.

Now we do have the option of using T-DXd in that first-line chemo setting for both the HER2‑low and ultralow patient population, in patients who are hormone receptor-positive.

[00:12:37]

HER2 Expression Today

And so, yes, this basically goes back to that initial diagram that I was showing you. Now I am not only doing care for patients who are HER2-positive, but it is now really important to note if they are HER2-low or ultralow, or less than 10% of cells with perceptible staining.

And keep in mind, this can be true from any prior biopsy. Often when I am annotating a chart, even if in the early-stage disease 20 years ago, if you saw HER2-low, I highlight that in my notes so that later down the line, I recall that I can use that to get T-DXd. So any prior biopsy does not have to be the most recent biopsy, is an important point.

[00:13:12]

Sacituzumab Govitecan: Efficacy and FDA-Approved Indications in Breast Cancer

And then what about sacituzumab govitecan? This is the TROP2 ADC that I mentioned that is approved in both triple-negative and HR-positive/HER2-negative. The data from triple-negative breast cancer comes from the ASCENT trial, which was a trial that looked at SG in patients with metastatic triple-negative who had had at least 2 lines of prior chemo. They had to have had a prior taxane. Stable brain mets were permitted.

This showed that SG outperformed chemotherapy, 5.6 vs 1.7 months, a hazard ratio of 0.41. And also demonstrated an impressive overall survival benefit in this population as well, 12.1 vs 6.7, a hazard ratio of 0.48. And so, this was approved, and full approval was in April 2021, is our current second-line standard of care for triple-negative breast cancer in most patients. You also have the option of using T-DXd in that patient population as well. And so, when to use SG vs when to use T-DXd depends on the context.

I tend to prioritize the use of sacituzumab govitecan in the second line for triple-negative. But if a patient has brain mets or other reasons where the schedule is more convenient for T-DXd or the side effect profile, T-DXd is also very appropriate to use in that second-line setting as well.

In the hormone receptor-positive/HER2-negative population, the TROPICS-02 trial is the relevant trial here. This was a later-line trial. Patients have had to have been on endocrine therapy and 2 to 4 lines of prior chemotherapy. This trial also was a positive trial showing that SG outperformed chemo, 5.5 vs 4.0 months. And also demonstrated about a 3-month overall survival benefit. This was also approved in February 2023 in this HR-positive/HER2-negative population.

For the triple-negative patients, I tend to prioritize T-DXd because the data just looked so good in both the last 2 trials I showed you, DESTINY-Breast04 and -06. I tend to use T-DXd first in the HR-positive/HER2-negative population and then tend to use SG later in this population. Of course, we have never compared these head-to-head. We are doing some cross-trial comparison and just the data we have available. There is also some controversy about using ADCs one after the other. Should we use them back-to-back? Should we put chemo in between? And we can touch on that later if we have time.

[00:15:38]

Dato-DXd: Efficacy and FDA-Approved Indication in Breast Cancer

And then Dato-DXd is now approved in hormone receptor-positive/HER2-negative breast cancer based on the TROPION-Breast01 trial. This was a trial that looked at patients who had metastatic hormone receptor-positive/HER2-negative breast cancer, 1 to 2 prior lines of systemic therapy had already progressed on their endocrine therapy, showed a benefit in PFS of 6.9 vs 4.9, hazard ratio of 0.63. There was no overall survival benefit in this trial. Keep in mind that in this trial, some patients were getting ADCs as standard of care since it was done a little bit later. Whether that was partially to blame for that or whether it just would not have been reached anyway, hard to say. But given the PFS benefit, this was FDA-approved as well about a year ago.

And so in general, again, I prioritize T-DXd for the hormone receptor-positive/HER2-negative. And then I think, whether to use DATO or saci later, again, they have never been compared head-to-head. Differences in schedule, differences in side effect profile. One has OS, one does not, although it is hard to compare that across trials. I often do discuss both with patients and then decide based on patient preference in this situation.

[00:16:58]

Where ADCs Fit Into HR+ MBC Treatment

Where do ADCs fit in hormone receptor-positive metastatic breast cancer? I definitely prioritize the use of T-DXd in the HER2-low and ultralow patient population. Keep in mind that even if all of the prior biopsies have read as IHC 0, often if you call the pathologist and ask them, can you look at all of these prior cases, often they can find at least one case that is ultralow.

I really do not sort of give up on T-DXd until I have really exhausted all options. And most of the time there is some biopsy that is read as ultralow upon re-review. And so, I tend to use T-DXd first in most patients. If they are truly IHC 0, you cannot get any ultralow reading. You have the option of SG or Dato-DXd and sort of, again, depending on the situation, either is reasonable. And then often if you do use T-DXd, you can come back around and use SG or Dato-DXd later as well.

[00:17:52]

Let’s Revisit a Question

Let us revisit a question.

[00:17:55]

Patient Case 1 Revisited: Patient With HR+/HER2-Ultralow Unresectable Breast Cancer

Going back to our first case, remember this patient is hormone receptor-positive, ER 85%, PR 20%, HER2 initially read as IHC 0 on endocrine therapy, but progresses in the brain at 6 months, and scans also show liver lesions, innumerable liver lesions, and a bone scan shows bone mets. Now, she is read as HER2-ultralow by IHC as shown here.

[00:18:22]

Posttest 2: Now, which of the following options would you recommend for this patient?

And so in this patient, HR-positive/HER2-ultralow with brain mets and liver lesions, which of the following therapies would you recommend?

1. Eribulin;
2. Single-agent chemo;
3. SG; or
4. T-DXd.

Please vote.

Speaker: The poll is open. Five more seconds. All right, thank you. We will close the poll and share the results.

Dr. Huppert: Great, so the most votes here are for T-DXd, followed by SG and then single-agent chemo. So excellent, yes, I agree completely. I would use T-DXd here.

This patient is HER2-ultralow. And so, based on the DESTINY-Breast06 trial, we have the option of using T-DXd in the first line in the ultralow population, especially with her innumerable liver lesions, brain mets, this is aggressive disease, and I would want to get the best control, and DESTINY-Breast06 showed that T-DXd outperformed chemo there.

[00:19:33]

So that is what I would also do here, excellent.

[00:19:38]

Novel Strategies: First-Line Therapy

And then what about moving ADCs earlier?

[00:19:42]

ASCENT-03: 1L Sacituzumab Govitecan vs CT for Pts With Advanced TNBC Ineligible for PD-1/PD-L1 Inhibitors

This year, we have seen some really exciting data in the triple-negative setting. Right now, we have ADCs approved in the second line being more effective than chemo, but should we be using them in the first line? And so, first, we will talk about ASCENT-03, which is looking at using sacituzumab govitecan vs chemo in the first-line setting for patients who are ineligible for PD-1 or PD-L1 inhibitors.

And so, this trial was presented at ESMO in 2025. And as you can see, the SG here is in the blue color, and the chemo is in orange. The SG in the first-line setting outperformed chemo, 9.7 vs 6.9 months, a hazard ratio of 0.62, which was statistically significant. So very impressive data there.

[00:20:31]

TROPION-Breast02: 1L Dato-DXd vs CT for Pts With Advanced TNBC Not Candidates for Immunotherapy

We also, you know, back-to-back at the same conference at ESMO, Rebecca Dent presented the data from TROPION-Breast02. This was looking at Dato-DXd in the first-line setting for triple-negative patients who are not candidates for immunotherapy.

And similarly, we saw an improvement in PFS here as well. Dato-DXd now being in blue, 10.8 vs 5.6, and a hazard ratio of 0.57, which was statistically significant.

And so, basically, neither of these is yet approved, but likely will be based on this impressive data. I very much anticipate that we are going to be seeing both of these agents available in the first-line setting for our triple-negative patients.

I will also mention that there was a trial presented at ASCO, ASCENT-04, looking at SG plus pembro, which was positive. And then the ongoing TROPION-Breast05 trial is looking at Dato-DXd plus durvalumab for PD-L1-positive patients.

So likely, I think it will be basically an ADC with or without immunotherapy as our first-line treatment in the future, although not yet FDA-approved. Unfortunately, I cannot quite get them, but I think hopefully one or both of these will be approved this calendar year so we can start using these for our patients.

[00:21:48]

InterACT Discussion

Please send your comments

So here, please send your comments. I definitely want to address any questions or comments.

[00:21:52]

Poll 3: Which of the following topics related to treatment would you like the faculty speaker and patient advocate to discuss?

But we have the option of choosing our own adventure here today. So, which of the following topics related to treatment would you like us to discuss?

1. How we talk to our patients about goals and priorities;
2. How to best check in with the patient starting therapy;
3. How we talk with our patients about the importance of adherence;
4. Patient perceptions of dose modifications, practice workflows to improve toxicity management, resources and strategies to help patient maintain adherence; or
5. Other.

Please vote about what would be most helpful for Mary Jane and me to discuss together with you all today.

Speaker: The poll is open. Five more seconds. All right. Thank you for your votes. We will now close the poll and share the results.

Dr. Huppert: Lots of options here. It looks like the top vote here is practice workflows that improve toxicity management and adherence. So, let us start with that.

So yes, practice workflows that improve toxicity management. Maybe I will start with what we do at UCSF and then, Mary Jane, would also love to get your input here as well.

I think for ADCs, the first thing I tell patients, of course, is that I explain it as a targeted form of chemotherapy. I explain that there is a target and then it has a payload. And so the idea is that it is pulling the payload closer to the cancer cell, ideally, to improve efficacy and decrease toxicity in an ideal world, but it is a form of chemotherapy. I think it is really important that patients understand that it is similar to chemo in many ways. And so, many of the side effects are like chemo, but they are unique to each particular agent.

I think in terms of practice workflow at UCSF, whenever we are starting a patient on chemo, we do a chemo teach with them, where our nurses go over the side effects. And we do as well, of course, as MDs. And I think that, I guess, going through each of the 3 ADCs we talked about, I will tell you the things I emphasize.

So I think for T-DXd, I emphasize that most common side effects are fatigue and nausea. We use a triplet anti-emetic nausea regimen. I use a lot of PO olanzapine as well, 2.5 mg at night for the first 5 to 7 nights can really sort of stave off the nausea. And I emphasize to patients, if what we are giving you is not enough, call us, let us know. We can definitely adjust or modify. Sometimes you do need to go down on the dose of the agent. Sometimes you do need to bring patients back in for day 7 fluids if they are really struggling. Sometimes you do need to add steroids. You can obviously titrate things as needed, but I do find that the olanzapine really does help. But just the low-dose 2.5 mg, sometimes you will need to go up to 5 mg, or sometimes I will even go down to 1.25 mg, if that makes them too drowsy.

I also talk about, you know, we need to do the cardiac monitoring every 3 months. I have rarely run into issues with that, but definitely important to do for T-DXd. And then the ILD risk, I emphasize strongly that there is about an 11-15% risk of interstitial lung disease or pneumonitis. Any cough, any shortness of breath, I want to know about it right away. And so, I tell that to the patients, their loved ones. And I really emphasize, do not wait for your next visit. Call our office or write to me right away.

We get scans more frequently on T-DXd. I typically do them every 9 weeks to evaluate for this because if you detect a grade 1 pneumonitis, which is defined as basically seeing it on imaging, but no symptoms, you can stop the drug, give steroids, re-scan. And as long as it is improved, you can re-challenge with T-DXd. We do have some re-challenge data.

Whereas with grade 2 pneumonitis, once they have symptoms, you need to permanently discontinue the drug, give steroids, etc. Scanning more frequently, hopefully, allows you to catch it earlier so that you have the opportunity to re-challenge, basically. And so, I think those are some of the key points and workflows that we utilize for T-DXd.

For sacituzumab govitecan, the side effects that I emphasize are fatigue, diarrhea, neutropenia, and alopecia. I think for the diarrhea, most of the time just sending patients with Imodium off the bat and counseling them, let us know if you have severe diarrhea. And occasionally, you need to escalate that and use other agents as well, or you need to dose-reduce if needed.

For the neutropenia, it is now in the label to give prophylactic growth factor off the bat. And so, I am giving everyone growth factor on this agent. In either, you can use short-acting growth factor or long-acting growth factor or both. Often, I will try to get away with long-acting on day 8, which might be enough, and that could cover them through the whole time. Sometimes people are neutropenic between day 1 and day 8, and you have to use short-acting, or sometimes insurance does not approve the long-acting. And so, sometimes I am either using both or short-acting after both day 1 and day 8. So depending on the situation, I will do different things, but really important to use growth factor to reduce the risk of neutropenia and febrile neutropenia in particular.

I think I will say alopecia is pretty uniform with sacituzumab govitecan, whereas with both T‑DXd and Dato-DXd, it is more 50-50 whether patients lose their hair, and often they lose only part of their hair or have more shedding or thinning. Whereas with SG, most patients do have complete alopecia. So, important to let patients know about that.

And then with Dato-DXd, the things I emphasize are stomatitis is number 1 for sure, nausea, and you do have to monitor for ocular toxicity and ILD are the 4 things.

So for stomatitis, using prophylactic steroid mouthwash is very key. So prescribing a dexamethasone steroid mouthwash, which we have patients use 4 times a day. And then that really helps reduce the incidence of stomatitis. If patients develop stomatitis despite that, you often do need to do a dose holder, dose reduction, and that really is effective. But the more you can prevent it off the bat with the steroid mouthwash, the better. So, I really, really do emphasize the prevention for all patients on that drug.

For the ocular toxicity, fortunately, it is pretty mild in most patients, and it is recommended to use a saline preservative or a preservative-free eyedrops, 4 times a day is how it was done in the studies. I will say for that one, my patients often are less compliant just because it is less of an issue. I think some people do it only once or twice a day, but I really do try to emphasize that it helps to use the eyedrops at least several times per day.

It is recommended to get an ocular exam around the time of study start is how it is worded, which I find is really helpful. Because if I want to start the drug, because the ocular toxicity incidence is lower than some of our other ADCs and other cancer types, you do not have to get them in before you start, you can actually start and then get them in a couple of weeks after that. And so, it should not limit your start. But we want to around the time of study, start an ocular exam, and then per the label, it is supposed to be once a year or as needed. So a less stringent ocular screening than with some of the other ADCs and other cancer types, but important to do and important to ask your patients about and counsel your patients about this.

And then the nausea, usually less severe than with T-DXd, and the ILD usually only about 3-4% in both of the trials. So about a quarter as often as with T-DXd, but similarly monitoring for it, trying to manage it like we do for T-DXd. So those are, I guess, some of the side effects tips that I would say.

Mary Jane, any specific advice for our clinicians about how, from the patient perspective, it helps to hear this or get some side effect data?

Mary Jane Steinhagen (Smart Patients): My experience, I have had metastatic breast cancer for 6 years. I am still on ribociclib and fulvestrant and doing very well.

Dr. Huppert: That is awesome. So you have not had to hear about these ones yet. That is great.

Mary Jane Steinhagen: Right. So what I found most helpful is the doctor prescribed ribociclib. She left. The next person to come in is the pharmacist who does the routine on the side effects and the whole thing. The third person who comes in in this practice is somebody who deals with the finances because CDK4/6 inhibitors are all uniformly very expensive. She said, "My job is to help you pay for them." And she is very good at her job.

I think the financial toxicity of drugs needs to be taken into account also. And if the practice has someone whose job it is to help secure funds, this will increase adherence to the drugs, which leads to a better outcome.

Dr. Huppert: Excellent. No, that is really, really wonderful. And it is nice that you actually got to meet that person. I feel like at our practice, we do not necessarily have that opportunity, but the more person-to-person connections to make that feasible is better. So that is a wonderful tip. Good.

[00:31:41]

InterACT Discussion

Please send your comments

Well, I think we have an opportunity for another Choose Your Own Adventure discussion. And any questions from the audience too, please do put them in the chat. Sorry, I have multiple screens here, so I cannot always see them, but we can definitely address them at the end.

Or if you have any specific questions about anything we are talking about, do put them in the chat.

[00:32:02]

Poll 3: Which of the following topics related to treatment would you like the faculty speaker and patient advocate to discuss?

So for our second poll, which of the following topics related to treatment would you like the faculty, speaker, and patient advocate to discuss?

Speaker: Dr. Huppert, this is the same one we just did. I will show the results again from it.

Dr. Huppert: Okay, perfect. The questions are different here.

Speaker: So they are. So it says poll 3. I am sorry. Let me see if this is the poll 4 that they have. Yes, okay. I did find it. It is after, just 1 second, I will get it up. It was after the other post questions. One second. Okay, the poll is launched.

Dr. Huppert: Wonderful. So another topic to discuss, please vote.

Speaker: Five more seconds. All right, thank you. We will close the poll and share the results.

Dr. Huppert: Great. So lots of enthusiasm for different topics here, but the winning topic is how to discuss treatment options and supporting evidence. And then the next most votes is clinical trials. We can maybe touch on both if we have time, but let us start with treatment options and supporting evidence for our patients.

Maybe, Mary Jane, I would love to start with you on this one, how you found it helpful that your medical providers talk about treatment options and supporting evidence from the patient perspective?

Mary Jane Steinhagen: I have the most common kind of breast cancer, which makes life easier for an oncologist. I also have very lazy cancer, which makes treatment easier for an oncologist. So my oncologist has simply said, "Given these 2 facts, this is what I would recommend." And we have had very good results with it.

I trust my oncologist. So she suggested this. We started it. And of course, when I get home, I do my own research and absolutely agreed with what she said. So in my case, I am very fortunate that I am a very simple oncology case. And I have been very pleased with the results of my drugs. It is working for me.

Dr. Huppert: That is wonderful. And I would love to hear, are there any particular, when you said you do your own research, any particular like websites or resources that you have found helpful as a patient that you direct other patients to?

Mary Jane Steinhagen: Yes. I belong to a support group run by breastcancer.org. And they have 4 sessions specifically for people with metastatic breast cancer.

Each session is moderated by 2 social workers. One moderates the group, and the other is the fact-checker. So that a patient can say, "Well, I am on a HER2." Okay, then in the chat will be clinical evidence about HER2 from a recognized cancer session. And at the end, after this support group is over, we are all emailed a copy with all of those links in.

So this support group, we actually did have somebody bring up ivermectin. However, she had been told there were no more options for her. So I can see her choosing that as a final gasp of desperation. But the moderator said, "It is your choice, but I want you to know this is not a standard of care." So, breastcancer.org does very good support, and it follows protocols. And you are not going to hear about any unusual, unapproved treatments without them being called out as such.

So that is a primary source for me. But I also then go, I look at clinical trials, and I look at the websites of the various drugs, and I do a lot of vocabulary work there because there are many words I do not know.

Dr. Huppert: Yes, yes. Those are excellent tips. Yes, breastcancer.org. I have also had patients that have really found their groups to be helpful. So that is a good tip for all. So wonderful. Thank you.

I guess I can say from my perspective, discussing treatment options and supporting evidence with patients, it really depends on the patient and what level of detail that they would like to hear from you and what level of exact findings. Do they want to look at the data slides, go through the trial with you, pull up the paper, or do they want to hear the overall big picture and have you guide them? I do think how I talk about it very much differs patient by patient.

At an academic center at UCSF, I have patients that are often very keen on knowing the specifics, knowing the data. So, often I am pulling up the trial. So if I have a patient, for example, where I am choosing between SG and Dato-DXd, I will tell them in the form of a positive or HER2-negative setting, I will say we have 2 options. We might also consider chemo. We have 3 options here. Here are the data for each. And sometimes I will even pull up the trial, I will pull up the tropics trial, I will pull up the TROPION-Breast trial, etc. And talk about, this was the efficacy, this was the toxicity, this is the schedule. And then this is option 2, toxicity, efficacy schedule or details. And then option 3, and then say, like, "These 2 have never been compared head-to-head, but here are the pros and cons."

And often patients say, "What would you do?" And I often will guide them based on what I know about them, "This might make sense for you, but this is also a great option." And it is a joint decision for sure.

And so I think again, whether I am actually pulling up the paper or pulling up the slides from the most recent meeting and going through at that level of data, I like to write things down a lot. So I will write option 1, option 2, option 3, and sort of summarize it. And then we often do decide together.

And then often what you do not use this time, you might use next time anyway. So I think it is a good exercise of showing the future as well. I have this roadmap for each type of breast cancer that I walk through with my patients.

When they are first diagnosed, I say, "This is the roadmap of how we treat hormone-positive/HER2-negative breast cancer. We are starting here at the first-line therapy, but we have all of these options in the future and how we choose them based on the mutation profile in endocrine therapy, later-line setting, based on your burden of disease, based on the options that are available." And so, I think at all points, I try to make clear that we are fortunate in breast cancer to have a lot of options. And so, we can make the best treatment decision based on their preferences and goals together at every point.

I do not know if that is sort of helpful to answer that piece of it. I can also touch on the clinical trial piece because often that is coming into play as well.

So if we have a clinical trial that I think would be a good option for our patients, I will throw that in the mix as well. Like I will say, "You know, unfortunately your scan showed progression." We talk through those. And as your next line of therapy, I usually say, "Here is what I would do per standard of care. We have option 1, option 2, option 3. Also, we have this option of this clinical trial, and let me tell you about that." And then we will go through the preliminary data or the details about that trial. Often it will be really important to talk about the schedule and the side effects. I emphasize that, of course, it is not yet FDA-approved. So, it is an experimental therapy. But if I do think it has promising elements that are maybe different than our standard, I sort of highlight those as well. And then I think patients will choose what they are feeling most comfortable with.

I think some patients like to try something new and different. And what I often say is it is an option that, you know, we can always come back around to the standard thing. So if we want to try a trial, we can do that now. And we can always come back to these other things later. Other patients that do not feel comfortable with trials would rather do the standard of care, the tried and true, the approved, if you will. And some patients choose not to do the trial.

So I think it just, again, there, depends on the patient. But I often do sort of phrase it as, "Here are our standards, here is a trial," you know, again, all of our options so that there is definitely no pressure to participate in the trial. But if they do participate in the trial or are interested in it, I will highlight what I think is unique about that trial, what I think the potential benefits are, as well as what are the known side effects, and what is the schedule. Many of our trials require more PKs, more visits. And so that is important too, if patients are coming from far. So I discuss that all in my treatment algorithm discussion.

Great, anything else to add, Mary Jane or …?

Mary Jane Steinhagen: No.

Dr. Huppert: Okay, perfect. So let us move on.

[00:41:34]

Insights Into Treatment of HER2-Negative/Ultralow/Low MBC From Patients and Caregivers

So insights into treatment of HER2-negative, ultralow, and low metastatic breast cancer for patients and caregivers.

So there were insights from a focus group of 10 patients and caregivers that talked about, you know, what do you wish you had known about ADCs? What are things that you want to convey to physicians? And some of the key insights are that one half of respondents reported that the doctor had never spoken with them about ADCs, which makes me feel really sad because these are great options for our patients.

And so, really important to be able to offer these, you know, whether that was they did not understand what is an ADC. And as Mary Jane mentioned, I think there is a lot of lingo and terminology that we are not very good as clinicians at throwing around, or whether they were not offered ADCs in the first place, I think, hard to know from here. But I think I really do try to talk to patients about what is an ADC and what are the options there. So, important to keep that in mind.

One-third of respondents reported that they have not feel well-informed about the latest breast cancer treatment options and available clinical trials, which also makes me sad. Community conversations suggested patients often must push for their preferences to be respected when deciding on treatment. And for one third of respondents, there was no explanation about whether their cancer was HER2-low or ultralow. So they did not understand that piece of it.

So I think, yes, the takeaway here is, I think it is important to bring up ADCs; important to inform our patients about different options. If your site does not have clinical trials, I think it is great to refer them early to a site that might, so that whether or not they want to consider a treatment now for the future, I think having that connection, being aware of the option of clinical trials is great. And of course, respecting patients' preferences along the way is critical.