Updates from the 2025 San Antonio Breast Cancer Symposium

Harold J. Burstein, MD, PhD breaks down the most meaningful updates from this year’s symposium—what’s new, what’s promising, and what may change care for those diagnosed with breast cancer. Caroline Koffke, RN, BSN, OCN, LBBC’s Director, Educational and Healthcare Provider Programs, moderated the conversation.

This free webinar is designed for:

• People diagnosed with early-stage or metastatic breast cancer
• Family, friends, and caregivers
• Anyone interested in the latest advancements in breast cancer care

You’ll learn:

• The most impactful scientific updates from SABCS
• What new research may mean for current or future treatment options
• How innovations in care may support quality of life
• Answers to questions during the Q&A

Transcript

Caroline Koffke, RN, BSN, OCN (00:00:10):

Dr. Burstein, welcome, and thank you so much for joining us this evening.

Harold J. Burstein, MD, PhD (00:00:14):

Caroline, I’m delighted to be here. Thank you for that gracious introduction. I’m looking at all the people posting where they’re from as they scroll in. We are coast to coast, north to south. It’s great to see. A shout out to everyone in Red Sox Nation, and we’re really glad to be with you. So thank you very much for asking me to join you.

(00:00:36):

It’s fun to be here with you. Sometimes people ask, Why San Antonio? And as a breast cancer investigator who’s now been to San Antonio like 29 times, it’s a good question. It’s a great city. No dissing San Antonio, though 29 times, I’m not sure I would’ve picked it. But originally back in the 1980s, there was a group of investigators at the University of Texas at San Antonio. And many of these people went on to become some of the most recognizable names in all of breast cancer translational research, people like Kent Osborne and George Sledge and others. But they were amongst the first to recognize that breast cancers often expressed estrogen receptor, and that by testing for estrogen receptor you could explain the results from a lot of trials, like using hormone therapies, and show that the hormone treatments worked in estrogen receptor-positive breast cancers but were not effective in tumors that were estrogen receptor-negative.

(00:01:40):

And so that work was foundational for, not quite everything, but a lot that’s happened in the past 30 or 40 years. As part of that, they began to organize an annual meeting. And in the first iteration of this they had like 60 people, and then it slowly grew.

(00:01:58):

My first San Antonio Breast Cancer Symposium was when I was a second-year fellow here in 1997. And at that time, the conference was about 800 people at the Rivercenter, one of the hotels on the River Walk in San Antonio. It has grown steadily. There are close to 10,000 people in person at the meeting every year. It really draws an international community of cancer specialists, international pharmaceutical partners, laboratory investigators, administrators, advocates. It’s a great meeting for advocates to attend.

(00:02:37):

The nice thing about San Antonio in comparison to other, even larger meetings is that most of the events happen one at a time, so you can actually go to almost all the talks. It’s all in one place. And if you go about your business, seeing the posters and going to the venue and things, you’ll run into everybody. It’s a who’s who of breast cancer and there really is the chance to see them.

(00:03:01):

I’m glad to be with you tonight, and I hope that in the future you’ll consider going to the San Antonio meeting, which is always a success.

(00:03:10):

As always, the meeting had lots and lots and lots of stuff. There are 3 full days of presentations. There are six poster sessions. There are seven rapid-fire rounds and all sorts of poster discussions and educational talks.

(00:03:27):

I’m not going to touch on everything. I’ve tried to pull out some of the studies I thought were most important. And, as it happens, this was on the heels of the ESMO meeting in Berlin in October where there was a huge number of presentations relevant to breast cancer, including the DESTINY-Breast11 trial and the DESTINY-Breast05 trial looking at the use of trastuzumab deruxtecan, or Enhertu, in early-stage HER2-positive breast cancer. We’ll talk briefly about that a little bit as well.

(00:04:01):

Having said all that, I’ve tried to keep my remarks reasonably short so that we have plenty of time for your questions. I’m very happy to tackle them, so I do hope that you will post in the Q&A, and I see that some people are already going at it. You guys are ahead of me here! We’re getting into Joe Sparano’s work on multi-platform AI. <laugh> There’s a lot to cover. And I don’t actually have slides from that, but I think it’s worth talking about.

(00:04:31):

So let’s get to it. Shall we?

(00:04:33):

Here’s some big trends to watch as you think about the particular studies that are forthcoming over the past year and into the near term.

(00:04:41):

The first is that we’re seeing a steady wave of antibody-drug conjugates supplanting traditional chemotherapy, particularly in metastatic disease. So we’ve seen drugs like trastuzumab deruxtecan, or Enhertu, march up the ladder from refractory HER2-positive disease to second-line HER2-positive disease to first-line HER2-positive disease. We’ve seen drugs like Trodelvy, or sacituzumab govitecan, prove their worth in first- and second-line triple-negative breast cancer, including in combination with immunotherapy, outperforming standard chemotherapy, traditional chemotherapy.

(00:05:26):

There’s a third antibody-drug conjugate, another Trop-2 targeted antibody conjugate, datapotamab deruxtecan, which is like if you were to have a blender and mixed together Trodelvy and Enhertu, you would end up with datopotamab because it’s a deruxtecan chemotherapy payload but a Trop-2 targeted antibody. And that has activity in first-line ER-positive breast cancer, as does trastuzumab deruxtecan. We don’t know which of these options is better.

(00:05:57):

These drugs have been moving up and displacing chemotherapy standards like capecitabine or paclitaxel as treatments of choice for many patients in those settings. And now they’re doing the same in some studies in earlier stage breast cancer, though usually in addition to chemotherapy.

(00:06:15):

A second big trend to watch is the treatment paradigm for HER2-positive metastatic disease where we’re looking more and more at induction phases of treatment and then highly effective maintenance strategies, which can extend and maintain that maintenance for very long runs, often years of runs in successfully treated patients, which is very exciting. And that really speaks to the activity of some of the newer drugs and the sensitivity of this disease to many of our existing treatments.

(00:06:50):

For early-stage breast cancer, we are seeing, and saw at San Antonio, the first report of a new class of drugs, oral SERDs in the early-stage setting, with the report of the giredestrant study called lidERA. They’re going to be, in the next 12 to 24 months, multiple studies that are reporting out for adjuvant use of oral SERDs versus traditional drugs like tamoxifen or an aromatase inhibitor. And so everyone is very keen to see how those studies come forward and shape up. This would be the first new class of drugs for targeting the hormonal therapy in early-stage ER-positive breast cancer since the aromatase inhibitors, which were first reported in 2002, so long overdue.

(00:07:39):

There’s much talk about de-escalation in breast cancer management, but I think it’s important to realize there are really two groups of patients that we’re talking about in breast cancer right now in the United States. The first is a group of patients who have screen-detected, early-stage ER-positive breast cancers. These are usually smaller tumors. They are usually in women age 40 to 75 because that’s who get screening in the United States. They are often caught real early, so they’re stage I, hopefully node negative. And in those patients, we are consistently showing that we can do less. We can do less in the way of surgery, most recently sparing even a sentinel lymph node biopsy for many of these patients. We can do less by avoiding chemotherapy based on very successful genomic assays like the Oncotype DX recurrence score. there’s shorter courses of radiation therapy. The so-called hypofractionated schedule of radiation at 15 days is now standard, but there are even shorter courses of partial breast or even whole breast radiation down to 5 days.

(00:08:53):

So for the local therapy, the early detection is allowing us to do less in the way of surgery and often a little bit less in the way of avoiding chemotherapy.

(00:09:03):

Having said that, most of the other half of this group of patients are patients who have higher risk disease, usually nodal involvement presenting with larger tumors. Around the world, this is a huge problem because many of the most populous nations on earth do not have screening mammography, and so most cases of breast cancer present with stage III or IV disease.

(00:09:26):

And in these higher risk cancers, there’s been a clear escalation of our systemic therapy, where we are adding CDK 4/6 inhibitors, we are adding SERDs for high risk ER-positive disease, perhaps. In triple-negative breast cancer, we are adding immunotherapy as neoadjuvant treatment, and in HER2-driven disease, we are beginning to think about where the antibody-drug conjugates belong.

(00:09:51):

I know that if you go to these meetings, you often hear a lot of talk about de-escalation, but I think it’s important to remember there is no actual agenda for de-escalation, particularly in medical oncology. What we’re trying to do is really tailor the amount of therapy we’re giving. So in low-risk breast cancers, where we can dial down some of the locoregional therapies and simplify these systemic adjuvant treatments, that’s a big opportunity. But a lot of the drug innovation space is in these higher risk, stage II or III cancers, particularly note positive and riskier cancers, and there we’re clearly escalating our therapies.

(00:10:28):

So, don’t buy all the rhetoric about deescalation, I guess.

(00:10:32):

Finally, and there are already some questions posted in the chat about this, there is mounting evidence for the possible roles of circulating tumor DNA testing in both early- and late-stage breast cancer and artificial intelligence models looking at pathology, in particular, and a little bit in radiology to try and supplement or refine clinical care. And I would say we’re getting close, but we’re not quite there yet. And by ctDNA here, I mean not the familiar liquid biopsies where they look for mutations, but particularly assays like the Signatera assay, which are looking for a readout on the presence or absence or quantification of circulating tumor DNA. And in that setting you can begin to see where this is going, but, personally, I do not think that those are parts of routine care for patients at this point. Though I’m interested in what the dialogue here will be.

(00:11:27):

So let me start by talking about that maintenance space of HER2-positive metastatic breast cancer.

(00:11:33):

There were two really important studies this year in that space. One was presented at San Antonio, the so- called HER2CLIMB study. This was a study that took patients who had HER2-positive metastatic breast cancer and randomized those patients after initial induction therapy with paclitaxel-trastuzumab-pertuzumab, or THP. And they got that for 4 to 8 months and then, assuming they’d had a treatment response and were not getting a tumor progression in any way, they were randomized to either the maintenance phase of trastuzumab-pertuzumab by itself or the addition of tucatinib, the small molecule tyrosine kinase inhibitor that targets the HER2 protein.

(00:12:15):

The endpoint here was progression-free survival. And what they showed was that by adding tucatinib to the trastuzumab-pertuzumab background, they could meaningfully improve the progression-free survival, the time until the cancer got worse, by close to 12 months. It was really quite a dramatic difference.

(00:12:34):

Numerically, tucatinib also had a tiny impact on brain metastases. I think there was perhaps the hope that there might be a more robust signal there. And this observation was particularly true in patients who had estrogen receptor-negative, HER2-positive breast cancer.

(00:12:53):

Now, tucatinib does have side effects, particularly lower GI side effects like colitis or diarrhea. And as yet, there really was no strong signal of survival benefit with the addition of tucatinib used in this particular way. We already use tucatinib as one of our second- or third-line options in HER2-positive metastatic breast cancer.

(00:13:14):

But I think the vision here, and we’ll see this in the next study as well, is that you induce a high rate of response with initial chemotherapy, trastuzumab-pertuzumab treatment, and then you peel off the chemotherapy and maintain that for a long arc of time with the antibody drugs and perhaps adding this targeted drug tucatinib as well.

(00:13:36):

The second study in this space, which was updated at San Antonio is the PATINA study. This was led by my Dana-Farber colleague, Otto Metzger. A very fundamentally similar design, six to eight cycles of chemotherapy and trastuzumab with or without pertuzumab, and then in patients who had had a induction response without progression, randomization to endocrine therapy plus trastuzumab, again, with or without pertuzumab, versus palbociclib, or Ibrance, in combination with the endocrine therapy and the HER2 antibodies.

(00:14:11):

What this study showed, again, was a major improvement in progression-free survival with the addition of the palbociclib to this cocktail. A strong argument for a maintenance approach that uses not just endocrine therapy but also includes the CDK 4/6 inhibitor in this treatment space.

(00:14:34):

Again, in the update here, they began to look numerically at whether there would be a reduction in the incidence of brain metastases. Fortunately, in both these studies, the incidence of brain metastases remains actually pretty low, and there was a numerical but not really statistically robust improvement in the incidence of later brain metastases here.

(00:14:53):

These studies are also notable in the context of the DESTINY-Breast09 trial. This was a study that looked at T-DXd, or trastuzumab deruxtecan, plus pertuzumab versus the taxane-trastuzumab-pertuzumab induction regimen. And this study, which reported out at ASCO 2025, showed that T-DXd plus pertuzumab achieved longer progression-free survival than did the THP. Now, for the clinical trial aficionados in the audience here, it’s important to note that the THP regimen was not continuous THP. They actually gave the THP for about eight cycles and then they stopped the chemo. So it was essentially a study of ongoing T-DXd with pertuzumab versus the THP followed by a maintenance phase of treatment that we just alluded to. And there was no overall survival difference, and essentially all these patients could have gotten T-DXd at some point down the road.

(00:15:57):

But what they showed here was that there was a higher rate of response and a longer period of tumor control with the T-DXd. And actually this week, the U.S. FDA approved T-DXd plus pertuzumab in the first-line setting for HER2-positive metastatic breast cancer.

(00:16:15):

Finally, one more study in the same vein. … Well, I’m going to pause on that.

(00:16:24):

Let me just say where I think we’re at here for first-line HER2-positive disease. The standard of care is going to be to give an induction phase of treatment. It could either be T-DXd with pertuzumab or with, THP, the taxane, trastuzumab, pertuzumab combination. After a good response, I think what most people are going to do is transition then to maintenance with trastuzumab and pertuzumab, because the cumulative side effects of the chemotherapy or the T-DXd become more difficult as time goes by.

(00:16:55):

And if it’s ER-positive, we would also then add endocrine therapy, and if it’s ER-positive, we could also add palbociclib. And conversely, if it’s ER-negative, in addition to the antibody therapies, we would probably add tucatinib. But I think that that maintenance phase is a really nice way of thinking about how to manage patients with newly diagnosed, advanced HER2-positive breast cancer.

(00:17:20):

One of the other questions has been, are these antibody-based regimens so active that we could actually skip the chemotherapy and just use endocrine therapy instead.

(00:17:30):

This was a small study from a German group, presented at San Antonio that randomized patients with HER2-positive metastatic breast cancer getting either first-, second-, or third-line therapy to chemotherapy with trastuzumab-pertuzumab or with endocrine therapy, plus one of the CDK 4/6 inhibitors, ribociclib, plus trastuzumab and pertuzumab.

(00:17:56):

What this study showed actually was that the hormone regimen was at least as good as the chemotherapy regimen. Now, many astarisces to point out here, some of these patients had already had some chemotherapy, and they were relatively endocrine therapy naive in the metastatic setting. But I think for many patients who have HER2-positive metastatic breast cancer, it’s a reminder that these patients are going to get lots and lots and lots of lines of therapy, and that for patients who have relatively mild, disease burdens at baseline, actually starting with endocrine therapy and the antibody therapies could be a nice option. They’re going to get T-DXd, chemotherapy, and all those other things with the antibodies, in the future, down the road.

(00:18:38):

Those were some of the highlights in HER2-positive advanced breast cancer. And here’s kind of a summary of some of the major studies in recent years, looking at the CLEOPATRA study, which was the one that put pertuzumab on the map, the DESTINY-Breast09 trial that compared T-DXd plus pertuzumab versus THP. Interestingly, there was a third arm in this study, trastuzumab deruxtecan alone. They have not reported out that result, and they actually announced that it wasn’t as good as the T-DXd with the pertuzumab. So it’s not just Enhertu monotherapy here. And then finally, the PATINA and the HER2CLIMB-05 trials, introducing that maintenance phase.

(00:19:28):

I think there are just a couple things more to note as you look at this. One is that these trials are global studies, they’re done around the world. And if you look, particularly outside the U.S., the vast majority of patients going on to these trials are patients who have de novo metastatic HER2-positive breast cancer. We still see that in the U.S. It’s actually a growing percentage of all metastatic HER2-positive breast cancer, and paradoxically, that is because women who have early-stage HER2-positive breast cancer who get effective treatment in the United States actually have a very low risk of recurrence of their disease because of the activity of trastuzumab and all the other derivatives.

(00:20:10):

So in the U.S., we don’t actually see nearly as much recurrent disease as we used to, and so more and more patients are de novo. And around the world, the vast majority, again, are de novo, are walking to the door with metastatic disease.

(00:20:26):

OK, so in the big scheme of things, they’re always trying to make these cartoons to suggest lines of therapy. Again, we’ve talked about this T-DXd plus pertuzumab or THP then the maintenance phase, and then you have a variety of options out back now, including older ADCs like T-DM1, tucatinib-based regimens if not already given, other chemotherapy and trastuzumab combinations, and other combinations with TKIs. So, obviously an exciting space where there’s been a lot of progress.

(00:21:00):

Before we leave HER2-directed antibody-drug therapy, we’ll focus on the early-stage studies that were presented in Berlin. One of them was the DESTINY-Breast11 study, which was a neoadjuvant trial that compared T-DXd, followed by THP versus dose-dense AC followed by THP versus T-DXd alone. And again, the T-DXd alone arm here was closed. It was not better than AC followed by THP. However, the T-DXd followed by THP neoadjuvant arm did have a slightly higher pathologic complete response rate, than did the, THP alone arm. in the U.S., our standard here has been TCHP, and it’s not exactly clear how T-DXd followed by THP would compare with TCHP, that’s Taxotere, carboplatin, trastuzumab, pertuzumab, and I think that still remains the standard.

(00:21:59):

Perhaps the more important study in Berlin as it relates to antibody-directed therapy for HER2-positive disease was the DESTINY-Breast05 trial. So this study was the first trial since the KATHERINE study for women who had had preoperative induction therapy for HER2-positive breast cancer with chemotherapy and trastuzumab.

(00:22:20):

And you may remember that in the KATHERINE study, those patients who had residual disease were randomized to either ongoing trastuzumab or to switch to the antibody-drug conjugate T-DM1, or Kadcyla. Kadcyla was the winner there, and in this study, they compared Kadcyla versus Enhertu, or T-DXd, in a large, randomized study of women who had had preoperative chemotherapy, trastuzumab, had residual disease in the breast or lymph nodes, and then were randomized. And what they showed here was that actually T-DXd outperformed the T-DM1. So I think that that will be an important practice-defining study. We’re already beginning to move patients who have significant amounts of residual disease after neoadjuvant Herceptin-directed therapy towards T-DXd. I think that’s really an important step forward as well.

(00:23:21):

So we’ll move now to the single most commercially anticipated study at the meeting, which was the lidERA study, a study of the oral SERD giredestrant for hormone receptor-positive HER2-negative early breast cancer. You have undoubtedly heard of oral SERDs. Fulvestrant is a SERD, a selective estrogen receptor degrader. It works by binding to the estrogen receptor and causing the cell machinery to break down the estrogen receptor. It’s a standard care, fulvestrant, but in multiple studies now, several of these oral SERDs, including imlunestrant and elacestrant and camizestrant have all shown that they can outperform fulvestrant in metastatic breast cancer, particularly in tumors that have acquired an ESR1 mutation, a mutation in the estrogen receptor.

(00:24:21):

So that story, which has been informed heavily by Rinath Jeselsohn here at Dana-Farber is that, as a mechanism of resistance to aromatase inhibitors, many tumors develop estrogen receptor mutations. I describe it to patients as though you’re putting your foot on the gas to accelerate it forward, and then you take your foot off but the pedal stays stuck to the ground because it’s perpetually on. And that’s what happens with these estrogen receptor mutations. They turn on the estrogen receptor even in the absence of estrogen. So it’s the way that the cell escapes from aromatase inhibitor therapy.

(00:24:59):

These drugs are now increasingly commercially available. Imlunestrant was FDA approved about 2 months ago, but none of them have yet reported out until last week on outcomes in the early-stage setting.

(00:25:11):

So the trial that looked at this was the lidERA study from Genentech Roche. It was a large 4,000 person randomized clinical trial for stage I, II, or III estrogen receptor breast cancer.

(00:25:25):

Now they went out of their way to enroll a very high risk group of patients, including women who had nodal involvement, women who had T4, which are large or locally advanced breast cancers, or women whose tumors had high risk scores on genomic assays like the mammoprint test or the Oncotype DX test. So this is not your ordinary lower risk, ER-positive breast cancers.

(00:25:51):

The randomization was to standard endocrine therapy, which could have been tamoxifen or an aromatase inhibitor, versus giredestrant for up to 5 years. Now, nearly all these women got chemotherapy because it was a higher risk patient population, and only 10% of the patients actually were enrolled in the United States. The vast majority were enrolled in Asia, Pacific, rest of world accrual.

(00:26:17):

I’m going to show some of the data here, because I think some of the details are really important. You’ll see that actually very few patients, well 40% were in the U.S., Canada, western Europe, but, again, only 10% were from the U.S. Forty percent were premenopausal. In general, these women, using various criteria, 70% had high risk breast cancers, and as I said, essentially all of them, or nearly all of them, 80% got chemotherapy as part of their treatment program. None of these women received CDK 4/6 inhibitors in the adjuvant setting.

(00:26:50):

So here’s the primary disease-free endpoint. Here’s the overall results, and here’s the magnified image. At 3 years, there was about a 3% separation between these curves, and 89% or 89.5%, up to 92.5% chance of being free from cancer recurrence, that’s a so-called hazard ratio of 0.7. So it reduced the risk of events by about 30%. And if you look at metastatic cancer-free survival, it made about a 2% difference.

(00:27:18):

So because this was such a big study with 4,000 patients, they were able to say that even a 2% difference here was statistically significant, though you have to do studies with thousands and thousands of patients to see that a relatively small difference like that emerges as statistically significant.

(00:27:37):

The company was clearly surprised that they had these data so early. There wasn’t the usual corporate buildup of anticipation about the news, in fact, they’d only released a press statement 10 days ago for the markets to suggest that they were going to have a positive study here. But the San Antonio meeting organizers did a really great job of hustling to get this presented at the meeting.

(00:28:00):

Now, one of the disappointments of this trial was that giredestrant’s toxicity looks a lot like that of aromatase inhibitors. Many people had hoped that it might be less toxic, but in fact, if you look at the incidence of arthralgias or headache or hot flashes and things, they were all roughly comparable between the standard-of-care endocrine treatments or giredestrant. So it’s not like this drug is so much better tolerated than tamoxifen or the AIs.

(00:28:29):

A couple of points here that I think are worth remembering, about this study. Again, it was a very high-risk patient population, relatively speaking, by stage, and not all the patients got what we would consider a real standard of care. A large fraction of the patients were actually given tamoxifen alone. Now, that is not inappropriate care, but usually in the United States, if a woman has a high-risk cancer such that they need chemotherapy and that you’re going to recommend more extensive treatment, the majority of those patients would be offered an aromatase inhibitor or ovarian suppression plus an aromatase inhibitor. And there was a disproportionate benefit with giredestrant compared to tamoxifen in contrast to the AIs.

(00:29:20):

A second point relates to that risk. This is a table I constructed just to make the point that in the United States many women who have node-positive breast cancer still have a very good prognosis. So if you have ER-positive breast cancer and you have one, two, or three positive nodes and a low Oncotype score, if you look at your rates of 5-year metastasis free survival, 94%, 95% of those women are cancer free at 5 years. If you look at some of these other trials like NATALEE, which was the adjuvant CDK 4/6 study, or monarchE, again, they really over-enrolled with very high-risk patients. The patients who entered that study had a risk of metastatic disease three to four times that of your average patient in the U.S. And the lidERA population is somewhere in between, but these are data with only 3 years. And they’re already having more events than your average patient in the U.S. So again, whether this drug is suitable for everyone is something we’re going to have to sort out.

(00:30:16):

And finally, this drug has, likely, an extraordinary cost. If you look at the currently approved treatments for breast cancer, elacestrant and imlunestrant, which are commercially available oral SERDs for metastatic disease, run you about $22,000 a month, whereas letrozole and tamoxifen are anywhere from $10 to a couple hundred bucks per month. One of the consequences here is that this drug, as well as the CDK 4/6 six inhibitors, which have very similar prices at around $20,000 to $22,000 a month, will represent huge public health expenditures for drugs that have some, but modest, benefit. And I think a really important question to be asked is, while no one is against progress, we all want the best treatments we can get, but is there a way to find less expensive pricing for these drugs, and how will this much money being spent on these drugs distort other opportunities for treatment in a resource strapped economy.

(00:31:28):

I don’t have the answers to that, but I think these are things that your group and others, which are very powerful advocates, might want to start exploring with the pharmaceutical companies, members of Congress, those kinds of things because the cost here is essentially going to take everything we do in breast cancer — screening, surgery, radiation therapy, chemotherapy, growth factors, genetic testing — and just dwarf the cost of all of that put together for these drugs if they become widely used, commercially. I don’t have the answer to that question, but it’s something to think about and be aware of.

(00:32:09):

Back to the metastatic setting. Data presented quite recently at the European meetings just a few weeks before, included a new drug called gedatolisib, which is a PIK3CA-targeting drug. And gedatolisib was compared to fulvestrant alone or fulvestrant plus palbociclib and gedatolisib in a randomized study called the VIKTORIA study. So there are a couple of commercially available PIK3CA inhibitors already in the market — alpelisib, capivasertib — this would be another one. And it too showed an improvement in progression-free survival.

(00:32:49):

The interesting thing about VIKTORIA-1 is that these patients had tumors that did not have PIK3CA mutations. There’s always been this question as to whether the activity of PIK3CA inhibitors was really limited to those patients who had PIK3CA mutations or not. This is the first study to show clinical evidence for activity outside of the PIK3CA-mutated tumor population. So, more to come about that.

(00:33:15):

Gedatolisib is not an incredibly convenient drug. It is an intravenous drug given 3 weeks in a row and then 1 week off. So there are considerations there as well. But that’s a drug you’ll be hearing a lot more about.

(00:33:28):

Finally, before we leave the topic of ER-positive metastatic disease, there was yet another study that compared chemotherapy in the first line versus endocrine therapy plus a CDK 4/6 inhibitor. Now, this is metastatic disease we’re talking about. The AMBRE study compared chemotherapy with either capecitabine or paclitaxel, versus endocrine therapy with abemaciclib and actually showed that the endocrine therapy did better than first-line chemotherapy.

(00:33:59):

A notable feature here is that all these patients actually had what was considered to be visceral metastases. That usually means the lung or the liver. It’s been the practice pattern for quite some time, but really for the vast majority of patients getting first-line treatment in ER-positive disease, even if there’s metastatic disease to viscera, chemotherapy should be deferred in favor of endocrine therapy with the CDK 4/6 inhibitor.

(00:34:24):

All right, now we’re switching gears to a different story about, antibody-drug conjugates. The ASCENT-03 trial, was a study of first-line triple-negative breast cancer for patients whose tumors were PD-L1 negative, such that they were not candidates for immunotherapy, because the standard of care for PD-L1 positive triple-negative disease in the metastatic setting is to give chemotherapy plus pembrolizumab, or Keytruda. This study compared sacituzumab govitecan, or Trodelvy, alone versus chemotherapy. It showed, again, an improvement in progression-free survival compared to chemotherapy. Very similar to what we’d seen in previous studies with sacituzumab in second line. We don’t really know whether it’s better to give sacituzumab in first or second line. I think either is a legitimate option right now, but the drug has activity in this space.

(00:35:16):

By contrast, the ASCENT-07 trial was a first-line study of sacituzumab in ER-positive metastatic breast cancer, and this study did not show that sacituzumab was better than chemotherapy. Other studies have shown that sacituzumab was more active in the second or third line setting. So standard chemotherapy or trastuzumab deruxtecan remain first-line choices for ER-positive metastatic disease. Saci could be a second-line option, though we know almost nothing about giving an ADC after a previous ADC exposure.

(00:35:54):

Another really nice study at the meeting was the so- called OlympiaN study, and this was a neoadjuvant study with olaparib, the PARP inhibitor, in women who had BRCA-associated breast cancers. So these are women who have known hereditary predisposition to breast cancer with a BRCA1 or BRCA2 mutation. They presented with tumors. They were randomized to olaparib alone, so not chemotherapy but just the oral PARP inhibitor, versus olaparib plus a checkpoint inhibitor and immunotherapy drug called durvalumab. And what this study showed is actually a very high rate of pathological complete response with olaparib alone. It was on the order of 50% to 60% and a little bit improvement with the durvalumab. What excited people about this was the idea that you might be able to spare patients who had BRCA-associated tumors from chemotherapy.

(00:36:53):

Now, the eagle-eyed amongst you will notice the problem here, which is there are only 25 patients in each of these arms. It’s the dilemma of doing studies in relatively rare situations of BRCA-associated breast cancer where the clinical team and the patient feel comfortable omitting chemotherapy as an initial part of the treatment plan. But it was a very provocative study, and I think you’ll see people building on this trial. Here are the actual numbers. So 68% path response rate with the olaparib alone, which is really quite remarkable.

(00:37:31):

OK. Another very interesting provocative study, probably not practice defining but provocative, was the WISDOM trial presented by Laura Esserman, who is the senior surgeon at University of California at San Francisco and a very innovative thinker for early-stage breast cancer. She’s been the intellectual force behind the I-SPY 2 trial. So as you know, screening mammography in the U.S, there are multiple different guidelines. Most recently, the United States Preventive Services Task Force and the American College of Radiology have endorsed beginning at age 40, usually with annual mammography. American Cancer Society is a little bit different. But usually we’re thinking about ages 40 to around 70 or 75 or even older if you’re in fabulous health. The point here is that we treat everybody the same. Irrespective of family history, irrespective of other health considerations, we make the same blanket guidelines.

(00:38:31):

What Laura has been developing is a study she calls the WISDOM Study where they were trying to more rationally set people up for screening. And they looked at risk factors including breast density, they had a health questionnaire that looked at family history, other health problems, whether or not she’d had previous breast biopsies, and a genomic panel looking for mutations in genes that might predispose to breast cancer or other high-risk features. And they classified patients into very low risk, average risk, high risk, or really high risk. In fact, most of the women who had hereditary predispositions obviously fell into the elevated or highest risk group. But then they prospectively stratified patients for screening — these are not women with breast cancer but they’re screening — into a lowest risk group where you didn’t start until age 50; an average risk group where you got every 2 year mammograms, which is the standard in much of Western Europe; or to annual mammograms with additional support from a breast health specialist or even annual mammograms plus an MRI.

(00:39:42):

What they showed is that, first of all, women could understand and work with this algorithm: that the satisfaction scores were very good, that people understood the idea if you’re at low risk, you need less than someone is at high risk. And when they actually looked at the outcome of screening, roughly 40,000 women in this experience, they saw the appropriate distribution of cancer diagnoses, and it didn’t seem like they were missing any. That is to say, they picked up the cancers they were supposed to pick up, and even though they had deferred the initiation of mammographic screening or done it less frequently in these low risk groups, they didn’t miss significant cancers.

(00:40:23):

Now, this is an exploratory study, even though it’s got 40,000 patients in it, but I think it opens the door to a real interesting discussion about ways of thinking about screening women. It must be acknowledged that this was a highly educated, highly motivated group of patients who really understood what was going on here. And as many of you know, one of the practical challenges in the U.S. is just getting women to come every year or two as it is, and the idea that you’re going to take them through an algorithmic-driven thing where they, some might not get any mammograms at all for another 10 years and others might shift to mammogram with an annual MRI is a complicated thing to implement at the public health level. But it’s probably an important exploratory study, and I think you’ll see a lot of interest in this kind of rational use of imaging in the future. And again, an area where the input of breast cancer survivors and patient advocates will be hugely valuable.

(00:41:28):

So in the last couple of slides — and then I hope you will post questions because I’m nearing the end of my remarks — places where we’re doing less surgery. You may be familiar with the SOUND and the INSEMA trial, and there was a third study presented at San Antonio called the AXSANA or EUBREAST study. And in these trials, what they all share is, they’re taking patients who have early-stage, newly diagnosed breast cancer, clinically stage I, they’re doing imaging of the axilla, like the ultrasound of the axilla. And if the axilla is negative, they are then randomizing patients to either sentinel lymph node surgery or skipping any sentinel node surgery or any axillary surgery at all.

(00:42:09):

What these studies have now consistently shown is that women who have low-risk tumors, who have a negative ultrasound of the axilla, can safely avoid sentinel lymph node surgery, even though roughly 10% to 15% of those women will have cancer in the sentinel lymph node. It’s just not clinically important because they will get radiation therapy and they will get endocrine therapy, these are almost all ER-positive cancers, and do quite well.

(00:42:35):

So the AXSANA or EUBREAST study also showed that, and there is no difference in the long-term outcomes here. So again, the surgeons have been able to move down, down from axillary node dissection to sentinel lymph node surgery to avoidance of sentinel lymph node surgery in a very rational way.

(00:42:53):

There was another trial trying to do less surgery for DCIS. This was a Japanese study and it was a registry. So women were diagnosed with DCIS and then they were followed without definitive surgery while on tamoxifen or other antiestrogen medicines. What they showed there was that at 5 years, actually, the risk of developing invasive breast cancer was 10%, which exceeded the threshold they had set for themselves of around 5% or 7%. So it turns out surgery for DCIS is still an important part of preventing a recurrence of this disease.

(00:43:26):

Finally, and it’s impossible to summarize the dozens of studies on circulating tumor DNA and artificial intelligence, but let me just give you the vibe of where things are going. With respect to circulating tumor DNA, there really are two discussions. One is about what we are now calling liquid biopsy, where, particularly in patients who have metastatic disease, we draw a tube of blood, and that allows the companies that manufacture these tests to look for the fragments of tumor DNA in the bloodstream and identify possible mutations in them, like an ESR1 mutation or a PIK3CA mutation, that could tailor therapy for those patients. That’s very standard and quite frequently done now for patients who have metastatic breast cancer.

(00:44:08):

The other kind of ctDNA testing, which is embodied in the Signatera test is looking for a readout — yes, no — on whether there is residual circulating tumor DNA as a surrogate for small occult bits of tumor DNA or tumor in the body. And the way they do this is they take the primary cancer and they sequence it and cancers have all these mutations, most of which are genetic noise, but they make a probe out of the unique mutations to your cancer. Then they take a tube of your blood and they run that probe in the blood to see if they find tumor DNA. Consistently, what they now show is that if you find a positive signal the chance of the cancer coming back in the future is higher. Makes sense, there’s still some -occult tumor in you. And if the tumor DNA test is negative or undetectable, your risk of the cancer coming back is lower, which again makes sense because they’re not finding viable tumor cells.

(00:45:04):

The problem is that it’s not clear that we know what to do with the information. Just because the test is negative doesn’t mean the cancer can’t come back. You should still, for instance, take adjuvant therapy. And conversely, just because the test is positive doesn’t mean the cancer is going to come back, and in fact, that’s the whole purpose of giving adjuvant therapy is fundamentally to treat occult metastatic disease and cure it.

(00:45:30):

So we’re getting closer and closer, but the testing is not routine at this point. And even though it is the single most frequent question I get from patients who are very sophisticated and spend a lot of time in chat rooms and social media dialogues and has been very heavily promoted by the company, none of the current guidelines actually recommend this use of the Signatera test for breast cancer patients at this time. I am hopeful that in a couple of years what we’ll see is, here’s a test, here’s the result, we know what to do with it. That’s the way we should think about this. We’re getting closer to that.

(00:46:06):

The other big area like this is artificial intelligence. And I think the first places you’re going to see artificial intelligence are pretty clear now. They are in radiology, particularly for mammogram screening, and in pathology, looking at the slides.

(00:46:22):

In radiology, there are now multiple, multiple studies showing that artificial intelligence is a pretty good reader of screening mammograms. It has the advantage of never getting tired, and it has the advantage of seeing things that the human eye seems a little unable to process quite as effectively. As you may know right now in the United States, screening mammograms are read by two radiologists. There’s a national shortage of radiologists to do this work, and so it often takes a lot of time to get the results back. But I think in the future, not too distant future, you’re going to see artificial intelligence become certified by the FDA as one of these backup readers. You’ll still have a human radiologist looking at the X-rays, but a second read will be done by an AI platform. And that probably will be helpful.

(00:47:12):

The other really exciting thing is that globally, as I mentioned at the outset, there are many countries that do not do screening mammography, but the availability of AI could radically change that because the cost and accessibility of doing imaging will change radically.

(00:47:28):

The other place is in pathology. And so what we saw in San Antonio were a couple of really provocative studies looking at some very well-known studies like NSABP B-20, which was the Joe Sparano data, where in addition to human pathology, or traditional pathology, and in addition to an Oncotype DX Recurrence Score, they could further squeeze out which cancer seemed risky and which did not by using an AI read of the pathology. So again, that was a small, exploratory-level analysis, but it shows the direction that I think a lot of things will be going where we’re using the AI to augment the traditional work of a pathologist or a radiologist.

(00:48:08):

I hope I’ve conveyed some of the excitement from the meaning, the rise of the antibody-drug conjugates, the new paradigm of maintenance treatment for HER2-positive metastatic disease, an emerging class of drugs in early-stage breast cancer about which you’ll be hearing a lot more, opportunities to de-escalate surgery and avoiding sentinel lymph nodes in many lower risk breast cancer patients newly diagnosed, but the escalation of a lot of other targeted therapies that we’re using in ER-positive and other breast cancers. And finally, growing evidence for some of these very cool technologies, circulating tumor DNA and artificial intelligence, almost but not quite there. It won’t be long as the guess.

(00:48:49):

So with that, Caroline, perhaps we will open the phones as they say and take whatever questions people have. I’ll try and end my sharing here.

Caroline Koffke, RN, BSN, OCN (00:48:59):

The phones are open. The phones are ringing. And I would just like to say that I would like to have you on speed dial always so that you can summarize everything as beautifully as you just did when questions arise. So thank you so much.

Harold J. Burstein, MD, PhD (00:49:12):

Happy to help.

Caroline Koffke, RN, BSN, OCN (00:49:12):

And just to be clear for everyone in the audience, this conference ended on Friday. It is Wednesday. So I just want to put into context what an absolute feat it is that Dr. Burstein was just able to summarize all of this research so beautifully. So thank you so much.

Harold J. Burstein, MD, PhD (00:49:28):

Thank you. That’s very kind.

Caroline Koffke, RN, BSN, OCN (00:49:29):

You will be shocked to hear that the number one thing we are getting in the Q&A is about ctDNA. <laugh>

(00:49:35):

And I know it’s not surprising. I’m sure that’s what your clinic days look like as well. I know you’ve summarized this, so I just want to get just some final sound bites from you to make sure that we have a really crystal clear explanation for our audience. So correct me if I’m wrong. In your metastatic patients, are you using ctDNA tests at this point in time?

Harold J. Burstein, MD, PhD (00:49:59):

Well, it depends which test you ask about. So every day, we order liquid biopsy — so that’s like the Guardant 360; it’s like Foundation One liquid biopsy — because we are looking for targeted mutations to go after in the tumor and we are looking for tumor mutational burden or other evolution of the tumor. And most patients who have metastatic cancer now are getting that testing done serially, multiple times, over the arc of their disease. That is standard. We do it every day.

Caroline Koffke, RN, BSN, OCN (00:50:29):

Great.

Harold J. Burstein, MD, PhD (00:50:29):

The question about using ctDNA to either quantify the tumor burden or to direct therapy in the early-stage setting in particular like: Do I have residual cancer? Can I skip the adjuvant treatment? The answer there is no, not yet. And I feel pretty strongly about that. There’s been a large literature over the decades. Some people have been paying attention like you guys have for a long time. They remember the circulating tumor cells, CTCs. Remember that? And they were doing bone marrow biopsies. And it turned out that women who had CTC, circulating tumor cells, in the bone marrow were more likely to have the cancer come back and those who didn’t were less likely to have the cancer come back, but it’s not a guarantee one way or the other. And it’s not clear what you do with the information.

Caroline Koffke, RN, BSN, OCN (00:51:19):

Mm-hmm.

Harold J. Burstein, MD, PhD (00:51:20):

So I think that if you want to do this, the first question you should ask yourself and your doctors, “What would I do with this piece of information if I find it?” And if the answer is, “I’m not going to do anything differently,” then you don’t need the test.

(00:51:37):

I understand and I get that everybody would like to have a negative test because it would be very reassuring and everyone would feel better. And that’s what drives most of the inquiries that I get. And I’ve ordered the test. There are patients who bring the test to me. We’re not trying to, we’re not standing there going like this. But I always frame this by saying, “I don’t care what the test says. Here’s what the recommendation is.” And the test rarely changes that.

(00:52:06):

So it’s not an out to avoid chemo, it’s not an out to avoid hormonal therapy in the early-stage disease, or other adjuvant treatment. And at the moment, we don’t know what to do with either a positive or a negative result. So that’s why I’m not ordering it for everybody. That doesn’t mean we don’t see patients bringing it in. And I will tell you that while many patients do, of course, find it reassuring, a test that comes back positive is distressing. And I’ve also seen situations where at baseline the tumor was tested and it was negative, and then they wanted to test again like 2 years later, it was positive, and they tested again like 6 months later, it was negative again. So these tests are not as perfect as you would imagine.

Caroline Koffke, RN, BSN, OCN (00:52:53):

That makes a whole lot of sense. And I really like how you summarize that you’re not going to change anything that you’re doing for that patient based on the results. So you really have to think when you’re going into the doctor and you want that test, what is that going to mean for you. I also like how you mentioned earlier that the future is hopefully very bright for these tests. We do have something actionable that we can do with that positive result. We’re just not there yet. That’s what all of these amazing trials are taking a look at.

Harold J. Burstein, MD, PhD (00:53:20):

Probably the first place in breast cancer is going to be in triple-negative disease, because it’s much more likely to liberate circulating tumor DNA than ER positive cancers. So I talked about the paradigm in HER2 positive, where if you have residual disease you go one way versus the other way and there’s some data in that for triple-negative. I think you’re going to see a similar story, which is stage II or III triple negative, you measure ctDNA at baseline, you measure it after the neoadjuvant therapy. If you’ve completely sterilized the ctDNA, then there will be studies to ask, do you need any more treatment or not. And in the patients who have residual cancer, on the ctDNA, same kind of questions and that’ll show where we can really use the test to decide things.

Caroline Koffke, RN, BSN, OCN (00:54:03):

Great. That’s really helpful. Thank you so much. I know it is always a hot, hot topic and you did a great job explaining that.

(00:54:09):

We also have a lot of questions about lobular breast cancer. Are there updates in lobular? Were lobular individuals included in any of the trials that you mentioned? I probably have about five or six questions about lobular.

Harold J. Burstein, MD, PhD (00:54:24):

To the second question, most of the ER-positive studies, be they metastatic or early-stage disease do include lobular cancers, and they usually are 5% to 10% of the patient population that enters the study because that’s the distribution of lobular breast cancer.

(00:54:40):

There was a very nice session, and if you have access to it, you can get it. It was what they call a poster discussion session on lobular breast cancer at the meeting. And there was a lot of work in looking at the different genomic profiles and other biologic profiles of lobular breast cancer versus ductal carcinoma.

(00:54:59):

So I think there are two takeaways from that work. One is that while we tend to think of most lobulars as lower grade, strongly ER positive and PR positive and HER2 negative, there is a group of lobular tumors that are biologically more aggressive. These emerge under the microscope as pleomorphic lobular breast cancers. They are sometimes HER2 positive or have mutations in HER2. They tend to be higher grade, they tend to have higher Oncotype scores and things like that. And when you look at the other patterns of gene expression, those tumors do have a different look.

(00:55:37):

The other big takeaway is that the differences between lobular and ductal clinically are real. They don’t look the same on a mammogram. They have slightly different patterns of metastasis to lymph node. The recurrence patterns are different. They tend to go to the gut, serosal surfaces like the lung and the abdomen. But the treatment principles aren’t unique. And so the question has been, can we find a treatment based signal that’s different. And so far that’s proving elusive.

(00:56:09):

I think we use the same kinds of tools — anatomic stage, histology, recurrence score testing — for making decisions in the early-stage setting. We know that hormone manipulations are critically important for these lobular tumors, but there isn’t like a different treatment paradigm for lobular versus low to intermediate grade ductal carcinomas for the most part.

Caroline Koffke, RN, BSN, OCN (00:56:33):

That’s very helpful. Thank you for that. I know we had a lot of questions.

(00:56:38):

Some questions about HER2 heterogeneity, we know that that can come up, as well as HER2 low. Anything new with that? I know obviously we have Enhertu approved in the HER2-low setting.

Harold J. Burstein, MD, PhD (00:56:48):

Yeah. So there’s HER2 positive … a million years ago, a long time ago in a galaxy far, far away. <laugh>

(00:56:56):

There was HER2 positive and there was HER2 negative. And then HER2 negative kind of got split, not because of new biology, but because of the activity of this drug, trastuzumab deruxtecan, or Enhertu, which had activity in HER2-low cancers. And these were cancers which were 2+ or 1+ but without FISH amplification and now they’ve pushed it down to “ultralow” where there’s just a whiff of expression.

(00:57:24):

The good news in my mind is I think we’re actually going back to HER2 positive and everybody else. Because this whole gradation of HER2 low doesn’t really … Any pathologist can repeat the test and if you whisper to them, “Does it look like there’s a little bit of HER2?” They go, “Yeah, maybe there’s a little bit. I guess you can call it low.”

(00:57:44):

There have been some beautiful studies like 2 years ago that — and this was beautiful science and a very special resource and I want to acknowledge how hard it is to do these studies and it’s sometimes tough to think about these studies — but they did autopsy studies of patients with metastatic breast cancer. They sampled metastatic spots from multiple areas of the bone or the liver, wherever the cancer was. And sometimes the cancer was HER2-zero and sometimes it was 1+ and 2+, that’s in the same cancer and the same person. It just speaks to the fact that I don’t think there’s really a biological thing there, or if there is, it’s because in different parts of the body there are clones that have grown one way or the other. So pretty much trastuzumab deruxtecan and sacituzumab govitecan and drugs like this, they work in these HER2-low, HER2-negative cancers.

(00:58:36):

So it’s not that we don’t test anymore, but I think there’s a little less there than met the eye in terms of thinking about is my cancer HER2-low or not. Almost any HER2 cancer, and almost any cancer in metastatic disease will be a candidate now for trastuzumab deruxtecan. HER2 positive, obviously; everybody else, the drug also works at least as well as first-line chemotherapy in that setting.

(00:59:00):

Maybe the most interesting new piece of data was a study from David Rimm, who’s a pathologist at Yale, and he has a very ultrasensitive way of testing for Trop-2 and for HER2 in individual cancer cells. And the interesting story was that the trastuzumab deruxtecan was most active the stronger the HER2 level of expression was and the lower the level of Trop-2. I don’t know what that means, but that particular constellation is where they saw the highest clinical rates of response with trastuzumab deruxtecan.

Caroline Koffke, RN, BSN, OCN (00:59:32):

That was very interesting. I didn’t know that, so thank you for that.

(00:59:35):

OK. So another HER2-directed question. Someone was asking about, what crosses the blood-brain barrier. We know that Enhertu does that. Am I right in saying that Datroway also has a little bit of data, the datapotamab?

Harold J. Burstein, MD, PhD (00:59:48):

Yeah. The blood-brain barrier probably exists in some ways, but after 250 years of looking under a microscope, no one’s ever seen it. So it’s important to remember that it’s not like Saran wrap that they see under the microscope. No one’s ever seen the blood-brain barrier. Empirically, we know that some drugs don’t penetrate, but that mostly describes the intact normal brain. When you have an infection or when you have metastasis to the brain, the blood supply is different, there’s a lot of inflammation. And so the real problem with brain metastases has been that this is a later stage phenomenon of more heavily resistant cancers usually, not always, but often. And, the drugs weren’t very good. So as the drugs have gotten better, we’re seeing much better responses.

(01:00:38):

So trastuzumab deruxtecan, Kadcyla, T-DM1, tucatinib, all these drugs have activity in the CNS. Other, older treatments also have activity in the CNS: doxorubicin chemotherapy, hormone manipulations, capecitabine chemotherapy, and again, some of the very newer ADCs like datopotamab and sacituzumab also seem to have some activity.

(01:01:04):

I think that the point here is that these drugs can be active. And, my friend, Nancy Lin, who has the office like 5 feet through that door.

Caroline Koffke, RN, BSN, OCN (01:01:16):

We love her.

Harold J. Burstein, MD, PhD (01:01:17):

She is very special and has done so much work in HER2-positive and other types of metastatic disease to the CNS. And I have eponymously called it the Nancy Lin rule, the Lin Law, which is that the best drug for the CNS is the best drug outside the CNS. There’s no drug that works magically in the brain that doesn’t work elsewhere. So if you actually step back, of course, she and her colleagues have done all these brilliant studies looking at drugs for the brain, but the way you find the best drugs to work in the brain is to find the best drugs that work outside the brain. And that’s the best one to move forward into the studies for the brain.

(01:01:59):

I think that’s a really important thing for patients to understand. There’s no magic thing that makes the drug work in the brain if it doesn’t work elsewhere. And conversely, if the drug is really good elsewhere, it often has activity in the CNS.

Caroline Koffke, RN, BSN, OCN (01:02:14):

You’re teaching me so much this evening.

(01:02:17):

We had a couple of questions that I know you touched on this, but just to kind of give us a brief summary. Sometimes triple-negative, we don’t get as many updates as with HER2 positive and HR positive. I know you talked about ASCENT-03, and then there was a vaccine trial. Can you just briefly summarize the big TNBC updates?

Harold J. Burstein, MD, PhD (01:02:34):

It was not a big meeting for TNBC, I’ll be honest on that.

Caroline Koffke, RN, BSN, OCN (01:02:37):

OK.

Harold J. Burstein, MD, PhD (01:02:37):

We saw over the past year, ASCENT-03 and ASCENT-04. Mm-hmm. So those were sacituzumab trials in first line —04 included pembro, 03 was just against chemo, both were positive studies. So again, Saci is my go-to first-line drug for triple-negative disease at this point. I think it’s a nice niche for that drug, though you need to give it with the growth factor support, otherwise it’s quite toxic.

(01:03:02):

In other news in triple-negative disease, this wasn’t a huge meeting. The vaccine studies are always provocative, but not clinically actionable at the current time.

(01:03:13):

You’re seeing, what they’re talking about are small numbers of patients, they induce an immune response, which seems like in a really important first step, unclear that we’re changing the natural history of the disease. There were some updates on some of the adjuvant immunotherapy trials, and there’s a lot of interest in TILs.

(01:03:35):

I guess this is the area of early-stage triple-negative breast cancer that there’s the most dialogue on. Everybody wants to measure TILS, which are tumor infiltrating lymphocytes. And those are … I’m sorry, there’s a helicopter landing. The hospital’s emergency helicopter pad is 50 yards outside my building.

Caroline Koffke, RN, BSN, OCN (01:03:54):

You’re at the center of medicine!

Harold J. Burstein, MD, PhD (01:03:55):

It’s not my private jet coming to take me home, I’m afraid.

(01:03:57):

But TILs are a very exciting marker in a lot of ways because they seem to identify patients who really, really get benefit from immunotherapy. It’s a marker for the body has a natural immune response going on. And if you hit that with the immune checkpoint inhibitors, that really seems to “Pow!” So I think you’ll see more and more interest in trying to refine how many TILs, what kind of TILs, all those kinds of things.

Caroline Koffke, RN, BSN, OCN (01:04:30):

Very interesting. Super cool to hear more about.

(01:04:34):

Our closing question. I know we still have so many unanswered questions, and I’m really sorry. We tried to get to as many as possible.

(01:04:40):

The closing question: If you had a crystal ball and worked at the FDA, so we’re we’re really hypothetical now, when are we going to see, so this giredestrant the lidERA phase III trial, when are we going to see that in the early-stage population?

Harold J. Burstein, MD, PhD (01:04:55):

OK, I was not going to get political here, but at the U.S. FDA, I’m not sure they’re endorsing the polio vaccine anymore. So, what they’re going to do about the lidERA trial, I have no idea.

(01:05:08):

And I gotta say, not in jest, I think there’s some real threats to the American public health and biotech sector. And again, this is an area where advocates could be very powerful because they are going backwards in our health, not forwards. And the idea that people shouldn’t be getting measles vaccines, my God, or polio vaccines or COVID vaccines is completely mistaken. You may have seen last week news from the CDC that there’d been a report that there were 10 deaths in the wake of the COVID vaccines. And then they actually updated that because the final report said, “Well, there were 10 deaths, but it’s not clear that more than four or five of them were even possibly related to the vaccine.” And just as a reminder, if you vaccinate like 50 million people, some of those people are going to die in the weeks immediately because they’re going to have other health issues that may or may not be related. So this is a real threat to your well-being and to the well-being of your family and your children. And it’s having a very corrosive effect because drug discovery, medical management of complicated diseases, look how much time you’ve spent as a community, your group and all the people on this call, to understand the nuances of breast cancer and early stage versus late stage and triple negative versus HER2-positive and genomic assays. That takes a lot of time and energy, and what they are actively trying to do is to make fools of us all, to pretend that people aren’t smart enough to understand this, and to imagine that artificial fake things can be substituted.

(01:06:47):

It’s one thing to say, “Oh, we need more rigor and stuff.” It’s another thing to say we’re throwing out decades worth of data. I had a patient in — I practice in Boston, so we probably are not representative of the nation as a whole — but I had a patient in, last week who was complaining about this, and she said, “My God, RFK Jr. said there are no data for the polio vaccines. I was on one of the polio vaccine trials! What are they talking about?” So this is something we have to be very afraid of.

(01:07:14):

Having digressed onto that, the question was what’s the FDA going to do. And the answer is, I don’t know.

(01:07:21):

If you look at the CDK 4/6 inhibitors, what the FDA did with the very first data was they sat on it for about a year, because they said, “We wanted to see 12 to 18 more months of follow up. We want to see that these curves continue to separate and we want to see how durable these benefits are.” It would not surprise me if they took a similar posture.

(01:07:45):

Now, in defense of giredestrant, it is a less toxic drug than the CDK 4/6 inhibitors, and so they may be less concerned about that. My guess is that it and other SERDs will ultimately get to the market, but whether that happens in 2026 or early 2027 or beyond, I don’t know.

Caroline Koffke, RN, BSN, OCN (01:08:04):

OK. Well, thank you so much. And I truly appreciate you also sharing your feedback on that because I think at this time more than ever, having a community of advocacy and ensuring that we are presenting trusted information that is medically backed, it couldn’t be more important right now. So thank you for saying that, and thank you for being our guiding voice and presenting us with the real facts and the real content as far as where we’re making progress in this space. We will continue, obviously, we will continue the fight on our end as well, in the advocacy platform.

(01:08:37):

But thank you so much for joining us tonight, Dr. Burstein. And for sharing your expertise, you are absolutely brilliant and we’re just really thankful. So much information shared at SABCS was impactful to a lot of us on this call, and it’s really amazing to have you help us understand it in a more user-friendly way.