Podcasts about pik3ca

Featuring perspectives from Dr Angela DeMichele, Dr Komal Jhaveri, Dr Erica Mayer, Dr Hope S Rugo and Dr Seth Wander, including the following topics:  Introduction (0:00) 1985 NCI Consensus Conference on Early Breast Cancer: Sir Richard Peto, FRS (2:01) Current Role of Genomic Assays in Treatment Decision-Making for Localized Hormone Receptor (HR)-Positive Breast Cancer — Dr DeMichele (5:13) Case: A premenopausal woman in her mid 40s with an ER-positive, HER2-negative, node-negative infiltrating ductal carcinoma (IDC) after partial mastectomy/radiation therapy who enrolls in the prospective, observational FLEX study: MammaPrint® low risk — Laurie Matt-Amaral, MD, MPH (15:30) Case: A premenopausal woman in her mid 40s after modified radical mastectomy for T2N0 ER-positive, HER2-negative IDC with an Oncotype DX® Recurrence Score (RS®) of 19 — Swati Vishwanathan, MD Case: A woman in her mid 60s with locally advanced (19 cm) ER-positive, HER2-low (IHC 1+) Stage IIIB mucinous carcinoma breast cancer and an RS of 18 — Alan B Astrow, MD (22:40) Role of CDK4/6 Inhibitors and Other Novel Strategies in Therapy for HR-Positive, HER2-Negative Localized Breast Cancer — Dr Jhaveri (30:18) Case: A woman in her mid 50s with ER-positive, HER2-negative Stage IIB, T2N1 IDC after neoadjuvant dose-dense AC-T, lumpectomy and adjuvant radiation therapy — Eleonora Teplinsky, MD (42:14) Case: A woman in her mid 60s with ER-positive, HER2-negative breast cancer with a surgically removed solitary lung metastasis after 4 years of adjuvant letrozole — Eric Fox, DO (46:32) Evolving Up-Front Treatment Paradigm for HR-Positive, HER2-Negative Metastatic Breast Cancer (mBC) — Dr Rugo (49:45) Case: A woman in her early 80s with Type 2 diabetes, well controlled hypertension and recurrent ER-positive, HER2-negative mBC after 4 years of adjuvant letrozole — Sunil Gandhi, MD (1:02:30) Clinical Utility of Agents Targeting the PI3K/AKT/mTOR Pathway for Patients with Progressive HR-Positive mBC — Dr Mayer (1:06:37) Case: A woman in her late 60s with ER-positive, HER2-low (IHC 1+), PIK3CA-mutant mBC with disease progression after 2 years of adjuvant letrozole — Laila Agrawal, MD (1:20:22) Case: A woman in her early 60s with ER-positive, HER2-low PIK3CA-mutant mBC and disease progression on first-line palbociclib/fulvestrant — Dr Teplinsky (1:26:36) Results from the Global Phase III lidERA Breast Cancer Trial of Giredestrant versus Standard Endocrine Therapy as Adjuvant Treatment for ER-Positive, HER2-Negative Localized Breast Cancer (1:31:48) Current and Future Role of Oral Selective Estrogen Receptor Degraders for Progressive HR-Positive mBC — Dr Wander (1:42:30) Case: A woman in her early 100s with locally advanced ER-positive, HER2-negative breast cancer with disease progression on letrozole, now with an ESR1 mutation — Dr Astrow (1:57:51) CME information and select publications

Featuring perspectives from Dr Javier Cortés, Dr Rita Nanda, Prof Peter Schmid and Dr Priyanka Sharma, including the following topics:  Introduction (0:00) Case: A woman in her early 80s with multiple comorbidities and triple-negative breast cancer (TNBC) develops bone-only metastases 4 months after declining capecitabine for post-neoadjuvant residual disease — Justin Favaro, MD, PhD (1:50) Case: A woman in her mid 70s with ER-negative, HER2-low (IHC 1+), PIK3CA-mutated, PD-L1-positive metastatic breast cancer (mBC) after receiving 3 cycles of neoadjuvant paclitaxel/carboplatin/pembrolizumab, which was discontinued — Alan Astrow, MD (6:47) Previously Untreated Metastatic TNBC (mTNBC) — Prof Schmid (10:47)  Case: A woman in her early 80s with multiregimen-recurrent ER-positive, HER2-low (IHC 1+) ESR1-mutant mBC receives sacituzumab govitecan — Jennifer Yannucci, MD (27:19) Case: The role of datopotamab deruxtecan (Dato-DXd) for patients with ER-positive, HER2-low mBC who experienced disease progression on prior trastuzumab deruxtecan (T-DXd) — Ranju Gupta, MD; Case: A woman in her late 70s with bilateral recurrence in the lungs of ER-negative, HER2-low (IHC 1+) breast cancer (PD-L1 TPS 20%) receives Dato-DXd with durvalumab on protocol — Yanjun Ma, MD, PhD (31:35) Integrating Antibody-Drug Conjugates (ADCs) into the Management of Endocrine-Resistant Hormone Receptor-Positive mBC — Dr Sharma (36:31) Case: A woman in her early 70s with recurrent ER-negative, HER2-low (IHC 2+) mBC receives sacituzumab govitecan and achieves complete remission — Dr Gupta; Case: Management of neutropenia associated with sacituzumab govitecan — Gigi Chen, MD (50:30) Case: A woman in her late 60s with recurrent ER-negative, HER2-low (IHC 1+) mBC (HER2 V69L mutation) receives T-DXd and achieves a complete response but develops Grade 1 interstitial lung disease — Dr Gupta; Case: Management of T-DXd-related side effects — Laila Agrawal, MD (54:10) Selection and Sequencing of Therapy for Relapsed/Refractory mTNBC — Dr Nanda (58:59) Case: A woman in her early 40s with multiregimen-recurrent ER-positive, HER2-low mBC who has experienced severe nausea with past treatments is about to initiate T-DXd — Atif M Hussein, MD, MMM (1:12:40) Tolerability and Other Practical Considerations with ADCs and Other Cytotoxic Agents for mBC — Dr Cortés (1:18:10) CME information and select publications

Dr. Monty Pal and Dr. Hope Rugo discuss advances in antibody-drug conjugates for various breast cancer types as well as treatment strategies in the new era of oral SERDs for HR-positive breast cancer. TRANSCRIPT Dr. Monty Pal: Hello, and welcome to the ASCO Daily News Podcast. I'm your host, Dr. Monty Pal. I'm a medical oncologist and vice chair of academic affairs here at the City of Hope Comprehensive Cancer Center, Los Angeles. Today, I'm thrilled to be joined by Dr. Hope Rugo, an internationally renowned breast medical oncologist and my colleague here at City of Hope, where she leads the Women's Cancers Program and serves as division chief of breast medical oncology. Dr. Rugo is going to share with us exciting advances in antibody-drug conjugates (ADCs) that are expanding treatment options in various breast cancer types. She'll also address some of the complex questions arising in the new era of oral SERDs (selective estrogen receptor degraders) that are revolutionizing treatment in the hormone receptor-positive breast cancer space. Our full disclosures are available in the transcript of this episode.  Dr. Rugo, welcome, and thanks so much for being on the podcast today. Dr. Hope Rugo: Thank you. Pleasure to be here. Dr. Monty Pal: So, I'm going to switch to first names if you don't mind.  The first topic is actually a really exciting one, Hope, and this is antibody-drug conjugates. I don't know if I've ever shared this with you, but I actually started my training at UCLA, I was a med student and resident there, and it was in Dennis Slamon's lab. I worked very closely with Mark Pegram and a handful of others. This is right around the time I think a lot of HER2-directed therapies were really evolving initially in the clinics. Now we've got antibody-drug conjugates. Our audience is well-familiar with the mechanism there but tell us about how ADCs have really started to reshape therapy for HER2-positive breast cancer. Dr. Hope Rugo: Yeah, I mean, this is a really great place to start. I mean, we have had such major advances in breast cancer just this year, I think really changing the paradigm of treating patients. But HER2-positive disease, we've been used to having sequenced success of new agents. And I think the two biggest areas where we've made advances in HER2-positive disease, which were remarkably advanced this year in 2025, have been in antibody-drug conjugates with trastuzumab deruxtecan and with new oral tyrosine kinase inhibitors (TKIs) that have less of a target on EGFR and more on HER2, so they have an overall more tolerable toxicity profile and therefore a potentially better efficacy in the clinic. At least that's what we're seeing with these new strategies that we couldn't really pursue in the past because of toxicities of the oral TKIs. So, although our topic is ADCs, I'm going to include the TKI because it's so important in our thinking about treating HER2-positive disease. In the metastatic setting, we've seen these remarkable improvements in progression-free and overall survival in the second-line setting with T-DXd, or trastuzumab deruxtecan, compared to T-DM1. And then sequencing ADCs with giving T-DXd after T-DM1 was better than an oral tyrosine kinase or a trastuzumab combination with standard chemotherapy. That was DESTINY-Breast03 and DESTINY-Breast02. So, then we've had other trials since then, and T-DXd has moved into the early-stage setting, which I'll talk about in just a moment. But the next big trial for T-DXd in HER2-positive disease was moving it to the first-line setting to supplant what has become an established treatment for now quite a long time: the so-called CLEOPATRA regimen, which used the combined antibodies trastuzumab, pertuzumab with a taxane as first-line therapy. And then we've proceeded on with maintenance with ongoing HP for patients with responding or stable disease. And we'd seen long-term data showing, you know, at 8 years there was a group of patients whose cancers had never progressed and continued improved overall survival. So, T-DXd was studied in DESTINY-Breast09, either alone or in combination with pertuzumab compared to THP. The patient population had received a little bit more prior treatment, but interestingly, not a lot compared to CLEOPATRA. And they designed the trial to be T-DXd continued until progression with or without pertuzumab versus THP, which would go for six cycles and then stop around six cycles, and then stop and continue HP. Patients who had hormone receptor-positive disease could use hormone therapy, and this is one of the issues with this dataset because, surprisingly in this dataset and one other I'll mention, very few patients took hormone therapy. And even in the maintenance trial, the HER2CLIMB-05, less than 50% took hormone therapy as maintenance. This is kind of shocking to me and highlights an area of really important education, that outcome is improved when you add endocrine therapy for hormone receptor-positive HER2-positive metastatic disease in the maintenance phase, and it's a really important part of treatment. But suffice it to say, you know, you're kind of studying continued chemo versus stopping chemo in maintenance. And T-DXd, as we all expected, in combination with pertuzumab was superior to THP in terms of progression-free survival, really remarkably improved. And you could stop the chemo with toxicity, but most people continued it with T-DXd. Again, not a lot of people got hormone therapy, which is an issue, and you stop the chemo in the control arm. So, this has brought up a lot of interest in trying to use T-DXd as an induction and then go to maintenance, much as we do with the CLEOPATRA regimen with hormone therapy. But it brings up another issue. So first, T-DXd is superior; it's a great treatment. Not everybody needs to have it because we don't know whether it's better to give T-DXd first or second with progression - that we need a little bit longer follow-up. But just earlier this week, interestingly, the third week of December, the U.S. FDA approved T-DXd in the DESTINY-Breast09 approach with pertuzumab. So as I mentioned earlier, there was a T-DXd-alone arm; that arm has not yet reported. So very interesting, we don't know if you need pertuzumab or not. So what about the maintenance? That's the other area where we've made a huge advance here. So, we all want to stop chemo and we want to stop T-DXd. You don't want somebody being nauseated for two years while they're on treatment, and also there's a small number of patients with mostly de novo metastatic HER2-positive disease who are cured of their disease. We'd like to expand that, and I think these new drugs give us the opportunity to improve the number of patients who might be cured from metastatic disease. So the first maintenance study we saw was adding palbociclib, the CDK4/6 inhibitor, to endocrine therapy and HP, essentially. There, we had a remarkable improvement in progression-free survival difference of 15.2 months: 29 to 44 months, really huge. At San Antonio this year, we saw data with this oral tyrosine kinase inhibitor tucatinib, already showed it was great in a triplet, but as maintenance in combination with HP, it showed also a remarkable improvement in progression-free survival. But the numbers were all shifted down. So in PATINA, the control arm was in the 24-month range; here it was the tucatinib-HP arm that was in the 25 months and 16 months for control. So there was a differential benefit in ER-negative and ER-positive disease. So I think we're all thinking that our ideal approach moving forward would be to give T-DXd to most patients, we see how they do, and treat to best response. And then, stop the T-DXd, start HP, trastuzumab, pertuzumab for ER-negative, with tucatinib for ER-positive with palbociclib. We also have early data that suggests that both approaches may reduce the development of brain metastases, an issue in HER2-positive disease, and delay time to progression of brain metastases as seen in HER2CLIMB-05 in very early data - small numbers, but still quite intriguing that you might delay progression of brain metastases with tucatinib that clearly has efficacy in the brain.  So, I think that this is a hugely exciting advance for our patients, and these approaches are quickly moving into the early stage setting. T-DXd compared to standard chemo, essentially followed by THP, so a sequenced approach resulted in more pathologic complete responses than a standard THP-AC-type neoadjuvant therapy. T-DXd alone for eight cycles wasn't better, and that's interesting. We still need the sequenced non-cross-resistant chemo. But I think even more importantly, the data from DESTINY-Breast05 looking at T-DXd versus T-DM1 in patients with residual disease after neoadjuvant HER2-targeted therapy showed a remarkable improvement in invasive disease-free survival with T-DXd versus T-DM1, and quite early. It was a high-risk population, higher risk than the T-DM1 trial with KATHERINE, but earlier readout with a remarkable improvement in outcome. We expect to be FDA approved sometime in the first half of 2026. So then we'll get patients who've already had T-DXd who get metastatic disease. But my hope is that with T-DXd, maybe with tucatinib in the right group of patients or even sequenced in very high-risk disease, that we could cure many more patients with early-stage HER2-positive breast cancer and cure a subset, a greater subset of patients with de novo metastatic disease. Dr. Monty Pal: That's brilliant. And you tackled so many questions that I was going to follow up with there: brain metastases, etc. That was sort of looming in my mind. I mean, general thoughts on an ADC versus a TKI in the context of brain mets? Dr. Hope Rugo: Yeah, it's an interesting question because T-DXd has shown quite good efficacy in this setting. And tucatinib, of course, had a trial where they took patients with new brain mets, so a larger population than we've seen yet for the T-DXd trials, and saw that not only did they delay progression of brain metastases and result in shrinkage of existing untreated brain mets, but that patients who develop a new brain met, they could stay on the same assigned treatment. They got stereotactic radiation, and then the patients who were on tucatinib with trastuzumab and capecitabine had a further delay in progression of brain mets compared to those on the placebo arm, even after treatment of a new one that developed on treatment. So, I think it's hard. I think most of us for a lot of brain mets might start with the tucatinib approach, but T-DXd is also a very important treatment. You know, you're kind of trading off a diarrhea, some liver enzyme elevations with tucatinib versus nausea, which you really have to work on managing because it can be long-delayed nausea, and this risk of ILD, interstitial lung disease, that's about 12%, with most but not all trials showing a mortality rate from interstitial lung disease of just under 1 percent. In the early-stage setting, it was really interesting to see that with T-DXd getting four cycles in the neoadjuvant setting, a lot less ILD noted than the patients who got up to 14 cycles, as I think they got a median of 10 cycles in the post-surgical setting, there was a little bit more ILD. But I think we're going to be better and better at finding this earlier and preventing mortality by just stopping drug and treating earlier with steroids. Dr. Monty Pal: And this ILD issue, it always seems to resurface. There are drugs that I use in my kidney cancer clinic, everolimus, common to perhaps the breast cancer clinic as well, pembrolizumab, where I think the pattern of pneumonitis is quite different, right? What is your strategy for recognizing pneumonitis early in this context? Dr. Hope Rugo: Well, it is, and you know, having done the very early studies in everolimus where we gave it in the neoadjuvant setting and we're like, "Hmm, the patient came in with a cough. What's going on?" You know, we didn't know. And you have mouth sores, you know, we were learning about the drug as we were giving it. What we don't do with everolimus and CDK4/6 inhibitors, for example, is grade 1 changes like radiation pneumonitis, we don't stop, we don't treat it. We only treat for symptoms. But because of the mortality associated with T-DXd, albeit small, we stop drug for grade 1 imaging-only asymptomatic pneumonitis, and some of us treat with a half dose of steroids just to try and hasten recovery. We've actually now published or presented a couple of datasets from trials, a pooled analysis and a real-world analysis, that have looked at patients who were retreated after grade 1 pneumonitis or ILD and tolerated drug very well and none of them died of interstitial lung disease, which was really great to see because you can retreat safely and some of these patients stayed on for almost a year benefiting from treatment. So, there's a differential toxicity profile with these drugs and there are risk factors which clearly have identified those at higher risk: prior ILD, for example. A French group said smoking; other people haven't found that, maybe because they smoked more in France, I don't know. And being of Japanese descent is quite interesting. The studies just captured that you were treated in Japan, but I think it's probably being of Japanese descent with many drugs that increases your risk of ILD. And, you know, older patients, people who have hypoxia, those are the patients. So, how do we do this? With everolimus, we don't have specific monitoring. But for T-DXd we do; we do every nine weeks to start with and then every 12 weeks CT scans because most of the events occur relatively early. Somebody who's older and at higher risk now get the first CT at six weeks. Dr. Monty Pal: This is super helpful. And I have to tell you, a lot of these drugs are permeating the bladder cancer space which, you know, is ultimately going to be a component of my practice, so thank you for all this. We could probably stay on this topic of HER2-positive disease forever. I'm super interested in that space still. But let me shift gears a little bit and talk about triple-negative breast cancer and this evolving space of HR-positive, HER2-low breast cancer. I mean, tell us about ADCs in that very sort of other broad area. Dr. Hope Rugo: So triple-negative disease is the absolute hardest subset of disease that we have to treat because if you don't have a great response in the early stage setting, the median survival is very short, you know, under two years for the majority of TNBCs, with the exception of the small percentage of low proliferative disease subsets. The co-question is what do we do for these patients and how do we improve outcome? And sacituzumab govitecan has been one strategy in the later line setting that was shown to improve progression-free and overall survival, the Trop-2 ADC. We had recently three trials presented with the two ADCs, sacituzumab govitecan and the other Trop-2 ADC that's approved for HR-positive disease, datopotamab deruxtecan. And they were studied in the first-line setting. Two trials with SG, sacituzumab govitecan, those trials, one was PD-L1 positive, ASCENT-04. That showed that SG with a checkpoint inhibitor was superior, so pembrolizumab was superior to the standard KEYNOTE-355 type of treatment with either a taxane or gemcitabine and carboplatin with pembrolizumab for patients who have a combined positive score for PD-L1, 10 or greater. So, these are patients who are eligible for a checkpoint inhibitor, and SG resulted in an improved progression-free survival.  The interesting thing about that dataset is that few patients had received adjuvant or neoadjuvant checkpoint inhibitor, which is fascinating because we give it to everybody now. But access is an issue and timing of the study enrollment was an issue. The other thing which I think we've all really applauded Gilead for is that there was automatic crossover. So, you could get from the company, to try and overcome some of the enormous disparities worldwide in access to these life-saving drugs, you could get SG through the company for free once you had blinded independent central review confirmation of disease progression. Now, a lot of the people who got the SG got it through their insurance, they didn't bill the company, but 80 percent of patients in the control arm received SG in the second-line setting. So that impacts your ability to look at overall survival, but it's an incredibly important component of these trials. So then at ESMO, we saw the data from SG and Dato-DXd in the first-line metastatic setting for patients who either had PD-L1-negative disease or weren't eligible for an immunotherapy. For the Dato study, TROPION-Breast02, that was 10 percent of the patients who had PD-L1-positive disease but didn't get a checkpoint inhibitor, and for the ASCENT-03 trial population it was only 1 percent. Importantly, the trials allowed patients who relapsed within a year of receiving their treatment with curative intent, and the Dato study, TB-02, allowed patients who relapsed while on treatment or within the first six months, and that was 15 percent of the 20 percent of early relapsers. The ASCENT trial, ASCENT-03, had 20 percent who relapsed between 6 and 12 months. The drugs were better than standard of care chemotherapy, the ADCs in both trials, which is very nice. Different toxicity profiles, different dosing intervals, but better than standard of care chemotherapy in the disease that's hardest for us to treat. And importantly, when you looked at the subset of early relapsers, those patients also did better with the ADC versus chemotherapy, which is incredibly important. And we were really interested in that 15 percent of patients who had early relapse. I actually think that six months thing was totally contrived, invented, you know, categorization and doesn't make any sense, and we should drop it. But the early relapsers were 15 percent of TB-02 and Dato was superior to standard of care chemo. We like survival, but the ASCENT trial again allowed the crossover to an approved ADC that improved survival and 80 percent of patients crossed over. In the Dato trial, they did not allow crossover, they didn't provide Dato, which isn't approved for TNBC but is for HR-positive disease, and they didn't allow, of course, pay for SG. So very few patients actually crossed over in their post-treatment data and in that study, they were able to show a survival benefit. So actually, I think in the U.S. where we can use approved drugs already before there's a fixed FDA approval, that people are already switching to use SG or Dato in the first-line setting for metastatic TNBC that's both PD-L1 positive for SG and PD-L1 negative for both drugs. And I think understanding the toxicity profiles of the two drugs is really important as well as the dosing interval to try and figure out which drug to use. Dr. Monty Pal: Brilliant. Brilliant. Well, I'm going to shift gears a little bit. ADCs are a topic, again, just like HER2-positive disease we could stay on forever. Dr. Hope Rugo: Huge. Yes. Dr. Monty Pal: But we're going to shift gears to another massive topic, which is oral SERDs. In broad strokes, right, this utilization of CDK4/6 inhibitors in the context of HR-positive breast cancer is obviously, you know, a paradigm that's been well established at this point. Where do we sequence in oral SERDs? Where do they fit into this paradigm? Dr. Hope Rugo: Ha! This is a rapidly changing area; we keep changing what we're saying every other minute. And I think that there are three areas of great interest. So one is patients who develop ESR1 mutations that allow constitutive signaling through the estrogen receptor, even when there's not estrogen around, and that is a really important mutation that is subclonal; it develops under the pressure of treatment in about 40 percent of patients. And it doesn't happen when you first walk in the door. And what we've seen is that oral SERDs as single agents are better than standard single-agent endocrine therapy in that setting. The problem that we've had with that approach is that we're now really interested in giving targeted agents with our endocrine therapies, not just in the first-line setting where CDK4/6 inhibitors are our standard of care with survival benefit for ribociclib and, you know, survival benefit in subsets with other CDK4/6 inhibitors, and abemaciclib with a numeric improvement. So we give it first line. The question is, what do you do in the second-line setting? Because of the recent data, we now believe that oral SERDs should be really given with a targeted agent. And some datasets which were recently presented, which I think have helped us with that, have been EMBER-3 and then the most recently evERA BC, or evERA Breast Cancer, that looked at the oral SERD giredestrant with everolimus compared to standard of care endocrine therapy with everolimus, where 100 percent of patients received prior CDK4/6 inhibitor and showed a marked improvement in progression-free survival, including in the subsets of patients with a short response, 6-12 months of prior response to CDK4/6 inhibitor and in those who had a PIK3CA pathway mutation. The thing is that the benefit looks like it's much bigger in the ESR1 mutant population, although response was better, PFS wasn't better in the wild type. So, we're still trying to figure that out. We also saw EMBER-3 with imlunestrant and abemaciclib as a second line. Not everybody had had a prior CDK4/6 inhibitor; they compared it to imlunestrant alone, but still the data was quite striking and seemed to cross the need for ESR1 mutations. And then lastly, we saw data from the single arms of the ELEVATE trial looking at elacestrant with everolimus and abemaciclib and showed these really marked progression-free survival data, even though single-arm, that crossed the mutation status. At least for the everolimus combination, abemaciclib analysis is still to come in the mutated subgroups. But really remarkable PFS, much longer.  Single-agent fulvestrant after CDK4/6 inhibitor AI has a PFS in like the three-month range and in some studies, maybe close to five months. These are all at 10-plus months and really looking very good. And so those questions are, is it ESR1 mutation alone? Is it all comers? We'd like all comers, right? We believe in the combination approach and we're learning more about combinations with drugs like capivasertib and other drugs as we move forward. Everybody now wants to combine their targeted agent with an oral SERD because they're clearly here to stay with quite remarkable data. The other issue, so the second issue in the metastatic setting is, does it make a difference if we change to an oral SERD before radiographic imaging evidence of progression? And that was the question asked in the SERENA-6 trial where patients had serial monitoring for the presence of ESR1 mutations in ctDNA. And those who had them without progression on imaging could be randomized to switch to camizestrant with the same CDK4/6 inhibitor or stay on their same AI CDK4/6 inhibitor. And they showed a difference in progression-free survival that markedly favored camizestrant. But interestingly, the people who were on the standard control arm had an ESR1 mutation, we think AIs don't work, they stayed on for nine more months. The patients who were on the camizestrant stayed on for more than 16 months. And they presented some additional subset data which showed the same thing: follow-up PFS data, PFS2, all beneficial in SERENA-6 at the San Antonio [Breast Cancer Symposium]. So, we're still a little bit unclear about that. They did quality of life, and pain was markedly improved. They had a marked delayed time to progression of pain in the camizestrant arm. So this is all a work in progress, trying to understand who should we switch without progression to an oral SERD based on this development of this mutation that correlates with resistance. And, you know, it's interesting because the median time to having a mutation was 18 months and the median time to switch was almost 24 months. And then there were like more than 3,000 patients who hadn't gotten a mutation, hadn't switched, and were still okay. So screening everybody is the big question, and when you would start and who you would change on and how this affects outcome. Patients didn't have access to camizestrant in the control arm, something we can't fix but we have experimental drugs. We're actually planning a trial, I hope in collaboration with the French group Unicancer, and looking at this exact question. You know, if you switch and you change the CDK4/6 inhibitor and then you also allow crossover, what will we see? Dr. Monty Pal: We're coming right to the tail end of our time here, and I could probably go on for another couple of hours with you here. But if you could just give us maybe one or two big highlights from San Antonio, any thoughts to leave our audience with here based on this recent meeting? Dr. Hope Rugo: Yeah, I mean, I talked about a lot of those new data already from San Antonio, and the one that I'd really like to mention which I think was, you know, there were a lot of great presentations including personalized screening presented from the WISDOM trial by my colleague Laura Esserman, fascinating and really a big advance. But lidERA was the big highlight, I think, outside of the HER2CLIMB-05 which I talked about earlier in HER2-positive disease. And this study looked at giredestrant, the oral SERD versus standard of care endocrine therapy as treatment for medium and high-risk early-stage breast cancer. And what they showed, which I think was really remarkable with just about a three-year median follow-up, was an improvement in invasive disease-free survival with a hazard ratio of 0.7. I mean, really quite remarkable and so early. It looked as though this was all driven by the high-risk group, which makes sense, not the medium risk, it's too early. And also that there was a bigger benefit in patients who were on tamoxifen compared to giredestrant versus AI, but for both groups, the confidence intervals didn't cross 1. There's even a trend towards overall survival, even though it's way too early. I think that, you know, really well-tolerated oral drug that could improve outcome in early-stage disease, this is the first advance we've seen in over two decades in the treatment of early-stage hormone receptor-positive disease with just endocrine therapy. I think we think that we don't want to give up CDK4/6 inhibitors because we saw a survival benefit with abemaciclib and a trend with giving ribociclib in the NATALEE trial. So we're thinking that maybe one approach would be to give CDK4/6 inhibitors and then switch to an oral SERD or to have enough data to be able to give oral SERDs with these CDK4/6 inhibitors for early-stage disease. And that's all in the works, you know, lots of studies going on. We're going to see a lot of data with both switching 8,000 patients with an imlunestrant switching trial, an elacestrant trial going on, and safety data with giredestrant with abemaciclib and soon to come ribociclib. So, this is going to change everything for the treatment of early-stage breast cancer, and I hope cure more patients of the most common subset of the most common cancer diagnosed in women worldwide. Dr. Monty Pal: Super exciting. It's just remarkable to hear how this has evolved since 25 years ago, which is really the last time I sort of dabbled in breast cancer.  Thank you so much, Hope, for joining us today. These were fantastic insights. Appreciate you being on the ASCO Daily News Podcast and really want to thank you personally for your remarkable contribution to the field of breast cancer. Dr. Hope Rugo: Thank you very much, and thanks for talking with me today. Dr. Monty Pal: You got it. And thanks a lot to our listeners today as well. You'll find links to all the studies we discussed today in the transcript of this episode. Finally, if you value the insights that you hear today on the ASCO Daily News Podcast, please rate, review, and subscribe wherever you get your podcasts. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinion of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Follow today's speakers:   Dr. Monty Pal @montypal Dr. Hope Rugo   @hoperugo Follow ASCO on social media:        ASCO on X  ASCO on Bluesky       ASCO on Facebook        ASCO on LinkedIn        Disclosures:     Dr. Monty Pal:    Speakers' Bureau: MJH Life Sciences, IntrisiQ, Peerview   Research Funding (Inst.): Exelixis, Merck, Osel, Genentech, Crispr Therapeutics, Adicet Bio, ArsenalBio, Xencor, Miyarsian Pharmaceutical   Travel, Accommodations, Expenses: Crispr Therapeutics, Ipsen, Exelixis   Dr. Hope Rugo:    Honoraria: Mylan/Viatris, Chugai Pharma   Consulting/Advisory Role: Napo Pharmaceuticals, Sanofi, Bristol Myer   Research Funding (Inst.): OBI Pharma, Pfizer, Novartis, Lilly, Merck, Daiichi Sankyo, AstraZeneca, Gilead Sciences, Hoffman La-Roche AG/Genentech, In., Stemline Therapeutics, Ambryx  

Dr. Juan Carlos Samamé, oncólogo médico de Lima, Perú, y vicepresidente de la Latin American Breast Cancer Association (LABCA), recibe al Dr. Antonio Llombart Cussac, jefe de servicio en el Hospital Arnau de Vilanova y coordinador en la Universidad Cardenal Herrera en Valencia, España. Juntos nos hablan sobre lo mejor en cáncer de mama, presentado en el marco del Simposio de Cáncer de Mama de San Antonio 2025, celebrado del 9 al 12 de diciembre de 2025 en San Antonio, Texas, Estados Unidos.Cáncer de mama luminal:lidERA Breast Cancer [1]EPIK-B5 [2]Cáncer de mama HER2:PHERGain [3] CLEOPATRA[4]PATINA[5]HER2CLIMB-05[6]ALTTO[7]Referencias:Giredestrant vs standard-of-care endocrine therapy as adjuvant treatment for patients with estrogen receptor-positive, HER2-negative early breast cancer: Results from the global Phase III lidERA Breast Cancer trial. https://sabcs.org/events/general-session-1/. Presentación científica (Abstract GS1-10). Presentado en el marco del Simposio de Cáncer de Mama de San Antonio 2025, celebrado del 9 al 12 de diciembre de 2025 en San Antonio, Texas, Estados Unidos.De Laurentiis M., Ferreira A. M., Gligorov, J., y cols. (2025, diciembre 9–12). Alpelisib plus fulvestrant for PIK3CA-mutated, HR-positive, HER2-negative advanced breast cancer after a CDK4/6 inhibitor (EPIK-B5): Phase III, randomized, double-blind, placebo-controlled, multicenter study (Abstract RF7-02). Presentado en el marco del Simposio de Cáncer de Mama de San Antonio 2025, celebrado del 9 al 12 de diciembre de 2025 en San Antonio, Texas, Estados Unidos.Llombart-Cussac, A., Pérez-García, J., Ruiz-Borrego., y cols. Circulating tumor DNA (ctDNA) in human epidermal growth factor receptor 2-positive (HER2[+]) Early Breast Cancer (EBC): Translational analysis of PHERGain neoadjuvant tailored treatment study (Abstract GS1-06). Presentado en el marco del Simposio de Cáncer de Mama de San Antonio 2025, celebrado del 9 al 12 de diciembre de 2025 en San Antonio, Texas, Estados Unidos.Rinnerthaler, G., Gampenrieder, S. P., Pichler, A., y cols. Clinical predictors for first-line treatment duration in HER2-positive metastatic breast cancer: Results from the AGMT_MBC-Registry. AGMT_MBC-Registry study (Abstract PS5-01-04). Presentado en el marco del Simposio de Cáncer de Mama de San Antonio 2025, celebrado del 9 al 12 de diciembre de 2025 en San Antonio, Texas, Estados Unidos.Metzger, O., Mandrekar, S., & Dockter, T. (2025, December 9–12). Central nervous system outcomes from the Phase III PATINA trial (AFT-38) (Abstract RF4-01). Presentado en la San Antonio Breast Cancer Symposium (SABCS) 2025; del 09 al 12 de diciembre de 2025; San Antonio, Texas.Hamilton E., Curigliano G., Martin M., y cols (2025). HER2CLIMB-05: A randomized, double-blind, phase 3 study of tucatinib versus placebo in combination with trastuzumab and pertuzumab as maintenance therapy for HER2+ metastatic breast cancer. Abstract GS1-01. Presentado en el marco del Simposio de Cáncer de Mama de San Antonio 2025, celebrado del 9 al 12 de diciembre de 2025 en San Antonio, Texas, Estados Unidos.Lambertini M, Samy F, Agostinetto E y cols. Adjuvant aromatase inhibitor or tamoxifen in patients with hormone receptor-positive/HER2-positive early breast cancer: An exploratory analysis from the ALTTO (BIG 2-06) trial. Abstract #GS1-03. Presentado en la San Antonio Breast Cancer Symposium (SABCS) 2025; del 09 al 12 de diciembre de 2025; San Antonio, Texas. Abstract GS1-09.

Welcome to the Oncology Brothers podcast! In this episode, we welcomed Dr. Neil Iyengar and Dr. Emily Gallagher, to dive deep into the world of PIK3CA and AKT pathway inhibitors for hormone receptor-positive (HR+) metastatic breast cancer. We discussed the latest approvals, including Inavolisib, Alpelisib, and Capivasertib, and explored their common side effects such as hyperglycemia, rash, and gastrointestinal issues. Our experts shared practical management strategies, dosing considerations, and the importance of patient education to ensure safe and effective treatment. Key topics covered in this episode: • Overview of PIK3CA and AKT inhibitors • Common side effects and their management • The significance of proactive patient education • Dosing strategies and when to consider dose modifications • Insights on managing hyperglycemia and gastrointestinal symptoms This episode is packed with valuable information to enhance your understanding of these important therapies in the breast cancer world. Don't forget to subscribe for more episodes on treatment algorithms, toxicities, and the latest in oncology! #PI3Kinhibitors #BreastCancer #Hyperglycemia #ToxCheck #MetastaticBC #OncologyBrothers #TargetedTherapy

Featuring an interview with Dr Priyanka Sharma, including the following topics: Patient-reported outcomes from the SERENA-6 trial of camizestrant with a CDK4/6 inhibitor for patients with HR-positive, HER2-negative advanced breast cancer and ESR1 mutations emerging during first-line endocrine-based therapy (0:00) Mayer E et al. Patient-reported outcomes (PROs) from the SERENA-6 trial of camizestrant (CAMI) + CDK4/6 inhibitor (CDK4/6i) for emergent ESR1m during first-line (1L) endocrine-based therapy and ahead of disease progression in patients (pts) with HR+/HER2– advanced breast cancer (ABC). ESMO 2025;Abstract 486MO. Imlunestrant and abemaciclib versus fulvestrant and abemaciclib for ER-positive, HER2-negative advanced breast cancer: An indirect treatment comparison of 3 Phase III trials (3:00) Bidard FC et al. Imlunestrant plus abemaciclib versus fulvestrant plus abemaciclib in estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer (ABC): An indirect treatment comparison (ITC) of three phase 3 trials. ESMO 2025;Abstract 496P . Giredestrant in the treatment of ER-positive, HER2-negative breast cancer: The Phase III evERA Breast Cancer and EMPRESS trials (5:39) Mayer E et al. Giredestrant (GIRE), an oral selective oestrogen receptor (ER) antagonist and degrader, + everolimus (E) in patients (pts) with ER-positive, HER2-negative advanced breast cancer (ER+, HER2– aBC) previously treated with a CDK4/6 inhibitor (i): Primary results of the phase III evERA BC trial. ESMO 2025;Abstract LBA16. Llombart-Cussac A et al. Preoperative window-of-opportunity study with giredestrant or tamoxifen (tam) in premenopausal women with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) and Ki67≥10% early breast cancer (EBC): The EMPRESS study. ESMO 2025;Abstract 294MO. Capivasertib/fulvestrant as first- and second-line endocrine-based therapy for PIK3CA/AKT1/PTEN-altered HR-positive advanced breast cancer in the CAPItello-291 trial and gedatolisib/fulvestrant with or without palbociclib for HR-positive, HER2-negative, PIK3CA wild-type advanced breast cancer in the VIKTORIA-1 trial.(10:25) Rugo HS et al. Capivasertib plus fulvestrant as first and second-line endocrine-based therapy in PIK3CA/AKT1/PTEN-altered hormone receptor-positive advanced breast cancer: Subgroup analysis from the phase 3 CAPItello-291 trial. ESMO 2025;Abstract 526P. Hurvitz SA et al. Gedatolisib (geda) + fulvestrant ± palbociclib (palbo) vs fulvestrant in patients (pts) with HR+/ HER2-/PIK3CA wild-type (WT) advanced breast cancer (ABC): First results from VIKTORIA-1. ESMO 2025;Abstract LBA17. CME information and select publications

Featuring slide presentations and related discussion from Prof Francois-Clement Bidard, Dr Hope S Rugo, Dr Rebecca Shatsky and Dr Seth Wander, including the following topics: Optimal approach to biomarker testing for patients with ER-positive metastatic breast cancer (mBC) (0:00) Case: A woman in her early 70s with recurrent ER-positive, HER2-negative mBC receives elacestrant (15:15) Case: A woman in her early 60s with ER-positive, HER2-low, PIK3CA-mutated mBC receives inavolisib-based therapy and experiences no disease progression for 24 months (18:02) Role of oral selective estrogen receptor degrader (SERD) monotherapy in the treatment of progressive ER-positive, HER2-negative mBC (26:26) Case: A woman in her mid 60s with recurrent HR-positive, HER2-negative mBC receives elacestrant (44:12) Case: A woman in her early 50s with recurrent HR-positive, HER2-negative, PIK3CA-mutant mBC receives capivasertib and fulvestrant (45:33) Potential novel applications of oral SERDs in the management of ER-positive, HER2-negative breast cancer (51:25) Case: A woman in her mid 50s with recurrent ER-positive, HER2-negative, PIK3CA-mutated mBC experiences disease progression 18 months after starting first-line letrozole and ribociclib (1:03:46) Case: A woman in her mid 50s with ER-positive, HER2-negative breast cancer undergoes serial ctDNA monitoring during first-line therapy (1:06:54) Tolerability and other practical considerations with oral SERDs (1:14:30) Case: A woman in her early 60s with recurrent HR-positive, HER2-negative mBC receives elacestrant (1:33:26) Case: A woman in her early 60s with recurrent HR-positive, HER2-negative mBC receives elacestrant (1:37:38) CME information and select publications

In this episode of the Oncology Brothers podcast, we are joined by Dr. Virginia Kaklamani from UT San Antonio to discuss the practice changing/informing findings from ESMO 2025, particularly in the realm of breast cancer. We dived deep into the most impactful studies, including: • MonarchE/NATALEE: Discover additional follow-up results from abemaciclib and ribociclib, where abemaciclib now has overall survival benefit in adjuvant HR+ settings. • Metastatic HR+ Disease: Insights on the latest data surrounding PIK3CA mutations, with results from the VIKTORIA1 trial with Gedatolisib, and evERA study with Giredestrant.  • HER2+ Breast Cancer: A comprehensive look at the DESTINY trials, highlighting the efficacy of Trastuzumab Deruxtecan (TDXd) in both neoadjuvant, adjuvant and palliative settings. • Triple Negative Breast Cancer: The role of sacituzumab and Dato-DXd in the first-line treatment landscape. Join us as we unpack these complex studies, discuss clinical implications, and share practical insights for community oncologists. Follow us on social media: •⁠  ⁠X/Twitter: https://twitter.com/oncbrothers •⁠  ⁠Instagram: https://www.instagram.com/oncbrothers •⁠  Website: https://oncbrothers.com/ Don't forget to like, subscribe, and hit the notification bell for more updates from the Oncology Brothers! #ESMO2025 #BreastCancer #MonarchE #NATALEE #DESTINYtrials #CDK4/6 #ADCs #OncologyBrothers

As part of the European Society for Medical Oncology (ESMO) Congress 2025, CancerNetwork® spoke with a variety of experts about key takeaways from different late-breaking abstracts, oral presentations, and other sessions focused on potential advancements across cancer care. Presenting investigators highlighted updated results from clinical trials evaluating novel therapeutic strategies across different cancer populations, including breast cancer and lung cancer.  Phase 3 VIKTORIA-1 Trial Sara A. Hurvitz, MD, FACP, the Smith Family Endowed Chair in Women's Health and senior vice president and director of the Clinical Research Division at the Fred Hutch Cancer Center, and tumor chair in breast oncology for the ONCOLOGY® editorial advisory board, first discussed findings from the phase 3 VIKTORIA-1 trial (NCT05501886). Her presentation highlighted how VIKTORIA-1 was “the first study to demonstrate a statistically significant and clinically meaningful improvement in progression-free survival [PFS] with PAM inhibition” for patients with PIK3CA wild-type advanced breast cancer. Data from the trial showed that gedatolisib plus fulvestrant (Faslodex) and palbociclib (Ibrance) produced a median PFS of 9.3 months (95% CI, 7.2-16.6) vs 2.0 months (95% CI, 1.8-2.3) with fulvestrant alone (HR, 0.24; 95% CI, 0.17-0.35; P

Featuring perspectives from Dr Aditya Bardia and Dr Adam M Brufsky, including the following topics: Introduction: Antibody-drug conjugates in localized breast cancer (0:00) Case: A frail woman in her late 70s with ER-positive, HER2-low metastatic breast cancer (mBC) receives sacituzumab govitecan after multiple lines of therapy — Eric Fox, DO (7:46) Case: A woman in her early 60s with NTRK-mutant ER-negative, HER2-low recurrent mBC receives trastuzumab deruxtecan — Lai (Amber) Xu, MD, PhD (21:07) Case: A woman in her mid 70s with PIK3CA-mutant recurrent metastatic triple-negative breast cancer who developed a diverticular abscess on neoadjuvant chemoimmunotherapy receives sacituzumab govitecan and pembrolizumab — Alan B Astrow, MD (31:49) Case: A woman in her mid 60s with ER-negative, HER2-low mBC receives sacituzumab govitecan after experiencing disease progression on capecitabine — Laila Agrawal, MD (38:37) Case: A woman in her late 50s with ER-negative, HER2-low mBC receives trastuzumab deruxtecan after experiencing disease progression on sacituzumab govitecan — Kimberly Ku, MD (44:24) Case: A woman in her early 60s with ER-positive, HER2-low mBC and hyperglycemia receives trastuzumab deruxtecan after experiencing disease progression on capivasertib/fulvestrant — Eleonora Teplinsky, MD (48:50) CME information and select publications

Host: Charles Turck, PharmD, BCPS, BCCCP Guest: Sarah Sammons, MD About 40 percent of patients with metastatic HR+/HER2- breast cancer have an activating mutation in the PIK3CA gene,1,2 which plays a key role not only in tumor growth, but also in driving resistance to endocrine therapy.3-5 And while there are several FDA-approved PI3K pathway-targeted agents for patients with PIK3CA tumor mutations,6-8 they come with challenges, like modest efficacy and on-pathway effects.9-12 Given this unmet need, the ReDiscover trial evaluated the investigational agent RLY-2608 in combination with fulvestrant in in patients with PIK3CA-mutated HR+/HER2- aBC previously treated with a CDK4/6 inhibitor.13 Joining Dr. Charles Turck to share updated safety and efficacy data from the trial is Dr. Sarah Sammons, a Senior Physician at the Dana-Farber Cancer Institute and an Assistant Professor of Medicine at Harvard Medical School in Boston. References: Vasan N, Cantley LC, Vasan N, Cantley LC. At a crossroads: how to translate the roles of PI3K in oncogenic and metabolic signalling into improvements in cancer therapy. Nat Rev Clin Oncol. 2022;19(7):471-485. doi:10.1038/s41571-022-00633-1 Network TCGA. Comprehensive molecular portraits of human breast tumours. Nature. 2012;490(7418):61-70. doi:10.1038/nature11412 Saal LH, Johansson P, Holm K, et al. Poor prognosis in carcinoma is associated with a gene expression signature of aberrant PTEN tumor suppressor …

CME credits: 0.75 Valid until: 07-10-2026 Claim your CME credit at https://reachmd.com/programs/cme/Case-in-Point-Applying-PI3K-Combinations-in-Early-Recurrent-HR-HER2-mBC/37336/ The PI3K-AKT-mTOR pathway is a crucial signaling network dysregulated in many cancers, promoting cell survival, growth, and proliferation, and often implicated in resistance to cancer therapies. Inhibition of this pathway by PI3K inhibitors disrupts a complex network of cellular processes that contribute to breast cancer, markedly reducing cell proliferation, promoting apoptosis, inhibiting angiogenesis, and ultimately preventing tumor formation and progression. In hormone receptor–positive (HR+), activating PIK3CA mutations occur in approximately 35% to 40% of patients and a variable prevalence across BC subtypes. Testing is thus crucial to ensure appropriate treatment selection. The development of PI3K-targeted agents may revolutionize the treatment landscape for HR+, HER2- metastatic breast cancer (mBC, and due to the recent approval of inavolisib, clinicians must be apprised of both the clinical evidence and best practices regarding the use of this agent. This activity has been designed to review the role of the PI3K-AKT-mTOR pathway in breast cancer, the importance of testing when making clinical decisions, and the role of PI3K-targeted therapies in HR+, HER- mBC.

CME credits: 0.75 Valid until: 07-10-2026 Claim your CME credit at https://reachmd.com/programs/cme/PI3K-Pathway-Inhibitors-Safety-and-Tolerability-Profiles/37338/ The PI3K-AKT-mTOR pathway is a crucial signaling network dysregulated in many cancers, promoting cell survival, growth, and proliferation, and often implicated in resistance to cancer therapies. Inhibition of this pathway by PI3K inhibitors disrupts a complex network of cellular processes that contribute to breast cancer, markedly reducing cell proliferation, promoting apoptosis, inhibiting angiogenesis, and ultimately preventing tumor formation and progression. In hormone receptor–positive (HR+), activating PIK3CA mutations occur in approximately 35% to 40% of patients and a variable prevalence across BC subtypes. Testing is thus crucial to ensure appropriate treatment selection. The development of PI3K-targeted agents may revolutionize the treatment landscape for HR+, HER2- metastatic breast cancer (mBC, and due to the recent approval of inavolisib, clinicians must be apprised of both the clinical evidence and best practices regarding the use of this agent. This activity has been designed to review the role of the PI3K-AKT-mTOR pathway in breast cancer, the importance of testing when making clinical decisions, and the role of PI3K-targeted therapies in HR+, HER- mBC.

CME credits: 0.75 Valid until: 07-10-2026 Claim your CME credit at https://reachmd.com/programs/cme/The-Future-of-PI3K-Inhibition-in-HR-HER2-Breast-Cancer/37339/ The PI3K-AKT-mTOR pathway is a crucial signaling network dysregulated in many cancers, promoting cell survival, growth, and proliferation, and often implicated in resistance to cancer therapies. Inhibition of this pathway by PI3K inhibitors disrupts a complex network of cellular processes that contribute to breast cancer, markedly reducing cell proliferation, promoting apoptosis, inhibiting angiogenesis, and ultimately preventing tumor formation and progression. In hormone receptor–positive (HR+), activating PIK3CA mutations occur in approximately 35% to 40% of patients and a variable prevalence across BC subtypes. Testing is thus crucial to ensure appropriate treatment selection. The development of PI3K-targeted agents may revolutionize the treatment landscape for HR+, HER2- metastatic breast cancer (mBC, and due to the recent approval of inavolisib, clinicians must be apprised of both the clinical evidence and best practices regarding the use of this agent. This activity has been designed to review the role of the PI3K-AKT-mTOR pathway in breast cancer, the importance of testing when making clinical decisions, and the role of PI3K-targeted therapies in HR+, HER- mBC.

CME credits: 0.75 Valid until: 07-10-2026 Claim your CME credit at https://reachmd.com/programs/cme/Double-Take-Pivotal-Data-Evaluating-PI3K-Inhibitor-Endocrine-Therapy-Regimens-in-mBC/37333/ The PI3K-AKT-mTOR pathway is a crucial signaling network dysregulated in many cancers, promoting cell survival, growth, and proliferation, and often implicated in resistance to cancer therapies. Inhibition of this pathway by PI3K inhibitors disrupts a complex network of cellular processes that contribute to breast cancer, markedly reducing cell proliferation, promoting apoptosis, inhibiting angiogenesis, and ultimately preventing tumor formation and progression. In hormone receptor–positive (HR+), activating PIK3CA mutations occur in approximately 35% to 40% of patients and a variable prevalence across BC subtypes. Testing is thus crucial to ensure appropriate treatment selection. The development of PI3K-targeted agents may revolutionize the treatment landscape for HR+, HER2- metastatic breast cancer (mBC, and due to the recent approval of inavolisib, clinicians must be apprised of both the clinical evidence and best practices regarding the use of this agent. This activity has been designed to review the role of the PI3K-AKT-mTOR pathway in breast cancer, the importance of testing when making clinical decisions, and the role of PI3K-targeted therapies in HR+, HER- mBC.

CME credits: 0.75 Valid until: 07-10-2026 Claim your CME credit at https://reachmd.com/programs/cme/Understanding-Endocrine-Resistance-in-HR-HER2-mBC/37323/ The PI3K-AKT-mTOR pathway is a crucial signaling network dysregulated in many cancers, promoting cell survival, growth, and proliferation, and often implicated in resistance to cancer therapies. Inhibition of this pathway by PI3K inhibitors disrupts a complex network of cellular processes that contribute to breast cancer, markedly reducing cell proliferation, promoting apoptosis, inhibiting angiogenesis, and ultimately preventing tumor formation and progression. In hormone receptor–positive (HR+), activating PIK3CA mutations occur in approximately 35% to 40% of patients and a variable prevalence across BC subtypes. Testing is thus crucial to ensure appropriate treatment selection. The development of PI3K-targeted agents may revolutionize the treatment landscape for HR+, HER2- metastatic breast cancer (mBC, and due to the recent approval of inavolisib, clinicians must be apprised of both the clinical evidence and best practices regarding the use of this agent. This activity has been designed to review the role of the PI3K-AKT-mTOR pathway in breast cancer, the importance of testing when making clinical decisions, and the role of PI3K-targeted therapies in HR+, HER- mBC.

CME credits: 0.75 Valid until: 07-10-2026 Claim your CME credit at https://reachmd.com/programs/cme/PI3K-Pathway-inhibition-in-HR-HER2-mBC-Mechanistic-Insights/37329/ The PI3K-AKT-mTOR pathway is a crucial signaling network dysregulated in many cancers, promoting cell survival, growth, and proliferation, and often implicated in resistance to cancer therapies. Inhibition of this pathway by PI3K inhibitors disrupts a complex network of cellular processes that contribute to breast cancer, markedly reducing cell proliferation, promoting apoptosis, inhibiting angiogenesis, and ultimately preventing tumor formation and progression. In hormone receptor–positive (HR+), activating PIK3CA mutations occur in approximately 35% to 40% of patients and a variable prevalence across BC subtypes. Testing is thus crucial to ensure appropriate treatment selection. The development of PI3K-targeted agents may revolutionize the treatment landscape for HR+, HER2- metastatic breast cancer (mBC, and due to the recent approval of inavolisib, clinicians must be apprised of both the clinical evidence and best practices regarding the use of this agent. This activity has been designed to review the role of the PI3K-AKT-mTOR pathway in breast cancer, the importance of testing when making clinical decisions, and the role of PI3K-targeted therapies in HR+, HER- mBC.

CME credits: 0.75 Valid until: 07-10-2026 Claim your CME credit at https://reachmd.com/programs/cme/Comprehensive-Biomarker-Testing-in-mBC-Informs-Clinical-Decision-Making/37332/ The PI3K-AKT-mTOR pathway is a crucial signaling network dysregulated in many cancers, promoting cell survival, growth, and proliferation, and often implicated in resistance to cancer therapies. Inhibition of this pathway by PI3K inhibitors disrupts a complex network of cellular processes that contribute to breast cancer, markedly reducing cell proliferation, promoting apoptosis, inhibiting angiogenesis, and ultimately preventing tumor formation and progression. In hormone receptor–positive (HR+), activating PIK3CA mutations occur in approximately 35% to 40% of patients and a variable prevalence across BC subtypes. Testing is thus crucial to ensure appropriate treatment selection. The development of PI3K-targeted agents may revolutionize the treatment landscape for HR+, HER2- metastatic breast cancer (mBC, and due to the recent approval of inavolisib, clinicians must be apprised of both the clinical evidence and best practices regarding the use of this agent. This activity has been designed to review the role of the PI3K-AKT-mTOR pathway in breast cancer, the importance of testing when making clinical decisions, and the role of PI3K-targeted therapies in HR+, HER- mBC.

CME credits: 0.75 Valid until: 07-10-2026 Claim your CME credit at https://reachmd.com/programs/cme/Double-Take-Pivotal-Data-Evaluating-PI3K-Inhibitor-Endocrine-Therapy-Regimens-in-mBC/37333/ The PI3K-AKT-mTOR pathway is a crucial signaling network dysregulated in many cancers, promoting cell survival, growth, and proliferation, and often implicated in resistance to cancer therapies. Inhibition of this pathway by PI3K inhibitors disrupts a complex network of cellular processes that contribute to breast cancer, markedly reducing cell proliferation, promoting apoptosis, inhibiting angiogenesis, and ultimately preventing tumor formation and progression. In hormone receptor–positive (HR+), activating PIK3CA mutations occur in approximately 35% to 40% of patients and a variable prevalence across BC subtypes. Testing is thus crucial to ensure appropriate treatment selection. The development of PI3K-targeted agents may revolutionize the treatment landscape for HR+, HER2- metastatic breast cancer (mBC, and due to the recent approval of inavolisib, clinicians must be apprised of both the clinical evidence and best practices regarding the use of this agent. This activity has been designed to review the role of the PI3K-AKT-mTOR pathway in breast cancer, the importance of testing when making clinical decisions, and the role of PI3K-targeted therapies in HR+, HER- mBC.

CME credits: 0.75 Valid until: 07-10-2026 Claim your CME credit at https://reachmd.com/programs/cme/Triple-Threat-Key-Data-on-Simultaneous-Estrogen-CDK4-6-and-PI3K-Inhibition-in-mBC/37335/ The PI3K-AKT-mTOR pathway is a crucial signaling network dysregulated in many cancers, promoting cell survival, growth, and proliferation, and often implicated in resistance to cancer therapies. Inhibition of this pathway by PI3K inhibitors disrupts a complex network of cellular processes that contribute to breast cancer, markedly reducing cell proliferation, promoting apoptosis, inhibiting angiogenesis, and ultimately preventing tumor formation and progression. In hormone receptor–positive (HR+), activating PIK3CA mutations occur in approximately 35% to 40% of patients and a variable prevalence across BC subtypes. Testing is thus crucial to ensure appropriate treatment selection. The development of PI3K-targeted agents may revolutionize the treatment landscape for HR+, HER2- metastatic breast cancer (mBC, and due to the recent approval of inavolisib, clinicians must be apprised of both the clinical evidence and best practices regarding the use of this agent. This activity has been designed to review the role of the PI3K-AKT-mTOR pathway in breast cancer, the importance of testing when making clinical decisions, and the role of PI3K-targeted therapies in HR+, HER- mBC.

CME credits: 0.75 Valid until: 07-10-2026 Claim your CME credit at https://reachmd.com/programs/cme/Case-in-Point-Applying-PI3K-Combinations-in-Early-Recurrent-HR-HER2-mBC/37336/ The PI3K-AKT-mTOR pathway is a crucial signaling network dysregulated in many cancers, promoting cell survival, growth, and proliferation, and often implicated in resistance to cancer therapies. Inhibition of this pathway by PI3K inhibitors disrupts a complex network of cellular processes that contribute to breast cancer, markedly reducing cell proliferation, promoting apoptosis, inhibiting angiogenesis, and ultimately preventing tumor formation and progression. In hormone receptor–positive (HR+), activating PIK3CA mutations occur in approximately 35% to 40% of patients and a variable prevalence across BC subtypes. Testing is thus crucial to ensure appropriate treatment selection. The development of PI3K-targeted agents may revolutionize the treatment landscape for HR+, HER2- metastatic breast cancer (mBC, and due to the recent approval of inavolisib, clinicians must be apprised of both the clinical evidence and best practices regarding the use of this agent. This activity has been designed to review the role of the PI3K-AKT-mTOR pathway in breast cancer, the importance of testing when making clinical decisions, and the role of PI3K-targeted therapies in HR+, HER- mBC.

CME credits: 0.75 Valid until: 07-10-2026 Claim your CME credit at https://reachmd.com/programs/cme/PI3K-Pathway-Inhibitors-Safety-and-Tolerability-Profiles/37338/ The PI3K-AKT-mTOR pathway is a crucial signaling network dysregulated in many cancers, promoting cell survival, growth, and proliferation, and often implicated in resistance to cancer therapies. Inhibition of this pathway by PI3K inhibitors disrupts a complex network of cellular processes that contribute to breast cancer, markedly reducing cell proliferation, promoting apoptosis, inhibiting angiogenesis, and ultimately preventing tumor formation and progression. In hormone receptor–positive (HR+), activating PIK3CA mutations occur in approximately 35% to 40% of patients and a variable prevalence across BC subtypes. Testing is thus crucial to ensure appropriate treatment selection. The development of PI3K-targeted agents may revolutionize the treatment landscape for HR+, HER2- metastatic breast cancer (mBC, and due to the recent approval of inavolisib, clinicians must be apprised of both the clinical evidence and best practices regarding the use of this agent. This activity has been designed to review the role of the PI3K-AKT-mTOR pathway in breast cancer, the importance of testing when making clinical decisions, and the role of PI3K-targeted therapies in HR+, HER- mBC.

CME credits: 0.75 Valid until: 07-10-2026 Claim your CME credit at https://reachmd.com/programs/cme/The-Future-of-PI3K-Inhibition-in-HR-HER2-Breast-Cancer/37339/ The PI3K-AKT-mTOR pathway is a crucial signaling network dysregulated in many cancers, promoting cell survival, growth, and proliferation, and often implicated in resistance to cancer therapies. Inhibition of this pathway by PI3K inhibitors disrupts a complex network of cellular processes that contribute to breast cancer, markedly reducing cell proliferation, promoting apoptosis, inhibiting angiogenesis, and ultimately preventing tumor formation and progression. In hormone receptor–positive (HR+), activating PIK3CA mutations occur in approximately 35% to 40% of patients and a variable prevalence across BC subtypes. Testing is thus crucial to ensure appropriate treatment selection. The development of PI3K-targeted agents may revolutionize the treatment landscape for HR+, HER2- metastatic breast cancer (mBC, and due to the recent approval of inavolisib, clinicians must be apprised of both the clinical evidence and best practices regarding the use of this agent. This activity has been designed to review the role of the PI3K-AKT-mTOR pathway in breast cancer, the importance of testing when making clinical decisions, and the role of PI3K-targeted therapies in HR+, HER- mBC.

CME credits: 0.75 Valid until: 07-10-2026 Claim your CME credit at https://reachmd.com/programs/cme/Triple-Threat-Key-Data-on-Simultaneous-Estrogen-CDK4-6-and-PI3K-Inhibition-in-mBC/37335/ The PI3K-AKT-mTOR pathway is a crucial signaling network dysregulated in many cancers, promoting cell survival, growth, and proliferation, and often implicated in resistance to cancer therapies. Inhibition of this pathway by PI3K inhibitors disrupts a complex network of cellular processes that contribute to breast cancer, markedly reducing cell proliferation, promoting apoptosis, inhibiting angiogenesis, and ultimately preventing tumor formation and progression. In hormone receptor–positive (HR+), activating PIK3CA mutations occur in approximately 35% to 40% of patients and a variable prevalence across BC subtypes. Testing is thus crucial to ensure appropriate treatment selection. The development of PI3K-targeted agents may revolutionize the treatment landscape for HR+, HER2- metastatic breast cancer (mBC, and due to the recent approval of inavolisib, clinicians must be apprised of both the clinical evidence and best practices regarding the use of this agent. This activity has been designed to review the role of the PI3K-AKT-mTOR pathway in breast cancer, the importance of testing when making clinical decisions, and the role of PI3K-targeted therapies in HR+, HER- mBC.

CME credits: 0.75 Valid until: 07-10-2026 Claim your CME credit at https://reachmd.com/programs/cme/Comprehensive-Biomarker-Testing-in-mBC-Informs-Clinical-Decision-Making/37332/ The PI3K-AKT-mTOR pathway is a crucial signaling network dysregulated in many cancers, promoting cell survival, growth, and proliferation, and often implicated in resistance to cancer therapies. Inhibition of this pathway by PI3K inhibitors disrupts a complex network of cellular processes that contribute to breast cancer, markedly reducing cell proliferation, promoting apoptosis, inhibiting angiogenesis, and ultimately preventing tumor formation and progression. In hormone receptor–positive (HR+), activating PIK3CA mutations occur in approximately 35% to 40% of patients and a variable prevalence across BC subtypes. Testing is thus crucial to ensure appropriate treatment selection. The development of PI3K-targeted agents may revolutionize the treatment landscape for HR+, HER2- metastatic breast cancer (mBC, and due to the recent approval of inavolisib, clinicians must be apprised of both the clinical evidence and best practices regarding the use of this agent. This activity has been designed to review the role of the PI3K-AKT-mTOR pathway in breast cancer, the importance of testing when making clinical decisions, and the role of PI3K-targeted therapies in HR+, HER- mBC.

CME credits: 0.75 Valid until: 07-10-2026 Claim your CME credit at https://reachmd.com/programs/cme/PI3K-Pathway-inhibition-in-HR-HER2-mBC-Mechanistic-Insights/37329/ The PI3K-AKT-mTOR pathway is a crucial signaling network dysregulated in many cancers, promoting cell survival, growth, and proliferation, and often implicated in resistance to cancer therapies. Inhibition of this pathway by PI3K inhibitors disrupts a complex network of cellular processes that contribute to breast cancer, markedly reducing cell proliferation, promoting apoptosis, inhibiting angiogenesis, and ultimately preventing tumor formation and progression. In hormone receptor–positive (HR+), activating PIK3CA mutations occur in approximately 35% to 40% of patients and a variable prevalence across BC subtypes. Testing is thus crucial to ensure appropriate treatment selection. The development of PI3K-targeted agents may revolutionize the treatment landscape for HR+, HER2- metastatic breast cancer (mBC, and due to the recent approval of inavolisib, clinicians must be apprised of both the clinical evidence and best practices regarding the use of this agent. This activity has been designed to review the role of the PI3K-AKT-mTOR pathway in breast cancer, the importance of testing when making clinical decisions, and the role of PI3K-targeted therapies in HR+, HER- mBC.

CME credits: 0.75 Valid until: 07-10-2026 Claim your CME credit at https://reachmd.com/programs/cme/Understanding-Endocrine-Resistance-in-HR-HER2-mBC/37323/ The PI3K-AKT-mTOR pathway is a crucial signaling network dysregulated in many cancers, promoting cell survival, growth, and proliferation, and often implicated in resistance to cancer therapies. Inhibition of this pathway by PI3K inhibitors disrupts a complex network of cellular processes that contribute to breast cancer, markedly reducing cell proliferation, promoting apoptosis, inhibiting angiogenesis, and ultimately preventing tumor formation and progression. In hormone receptor–positive (HR+), activating PIK3CA mutations occur in approximately 35% to 40% of patients and a variable prevalence across BC subtypes. Testing is thus crucial to ensure appropriate treatment selection. The development of PI3K-targeted agents may revolutionize the treatment landscape for HR+, HER2- metastatic breast cancer (mBC, and due to the recent approval of inavolisib, clinicians must be apprised of both the clinical evidence and best practices regarding the use of this agent. This activity has been designed to review the role of the PI3K-AKT-mTOR pathway in breast cancer, the importance of testing when making clinical decisions, and the role of PI3K-targeted therapies in HR+, HER- mBC.

Featuring case presentations and related discussion from Dr Sara A Hurvitz and Dr Sara M Tolaney, including the following topics: Case: A woman in her mid 50s with localized HR-negative, HER2-positive breast cancer — Dr Tolaney (0:00) Case: A woman in her mid 40s with localized HR-positive breast cancer with a germline BRCA2 mutation — Dr Tolaney (7:08) Case: A woman in her early 30s with HR-negative, HER2-positive metastatic breast cancer with one isolated liver metastasis — Dr Tolaney (11:30) Case: A woman in her early 50s with metastatic triple-negative breast cancer — Dr Tolaney (17:52) Case: A woman in her early 30s with localized HR-positive, HER2-negative breast cancer — Dr Hurvitz (31:49) Case: A woman in her early 60s with HR-positive, HER2-negative metastatic breast cancer with concurrent PIK3CA and ESR1 mutations — Dr Hurvitz (40:39) Case: A woman in her early 40s with recurrent HR-positive advanced breast cancer with a PIK3CA mutation — Dr Hurvitz (51:28) Case: A woman in her early 50s with HR-positive, HER2-negative breast cancer eligible for the SERENA-6 switching strategy — Angela DeMichele, MD, MSCE (58:41) CME information and select publications

Love the episode? Send us a text!In this special episode of Breast Cancer Conversations, host Laura Carfang speaks with Dr. Troso  about the evolving role of DNA testing in breast cancer care. Together, they break down the three main types of testing:Hereditary genetic testing: Identifying inherited mutations such as BRCA1, BRCA2, and PALB2 (among others) that increase cancer risk and influence prevention and treatment decisions.Somatic (tumor) testing: Analyzing mutations within the tumor itself—such as PIK3CA or ESR1 mutations—to guide targeted therapies and manage resistance in advanced disease.Circulating tumor DNA (ctDNA) testing: Also known as a liquid biopsy, this emerging tool uses blood tests to detect cancer DNA fragments. It holds promise for monitoring recurrence, guiding treatment earlier, and advancing clinical trials.Tune into this Special! 

“She's triple negative and has a very, very aggressive tumor. Instead of going on spring break that year, she sat in our chemo room and got chemo. Her friends from college are good to try to keep her involved and try to surround her and encourage her, but they're right now in very, very different spots in their lives. She's fighting for her life; her friends are fighting for the grade they get in a class—and that's different,” ONS member Kristi Orbaugh, MSN, NP, AOCN®, AOCNP®, nurse practitioner at Community Hospital North Cancer Center in Indianapolis, IN, told Jaime Weimer, MSN, RN, AGCNS-BS, AOCNS®, manager of oncology nursing practice at ONS, during a conversation about metastatic breast cancer in adolescent and young adult patients. Music Credit: “Fireflies and Stardust” by Kevin MacLeod Licensed under Creative Commons by Attribution 3.0  This podcast is sponsored by Lilly and is not eligible for NCPD contact hours. ONS is solely responsible for the criteria, objectives, content, quality, and scientific integrity of its programs and publications. Episode Notes This episode is not eligible for NCPD. ONS Podcast™ episodes: Episode 368: Best Practices for Challenging Patient Conversations in Metastatic Breast Cancer Episode 354: Breast Cancer Survivorship Considerations for Nurses Episode 350: Breast Cancer Treatment Considerations for Nurses Episode 345: Breast Cancer Screening, Detection, and Disparities Episode 307: AYAs With Cancer: Financial Toxicity Episode 300: AYAs With Cancer: End-of-Life Care Planning ONS Voice articles: ‘Cancer Ghosting' May Add Another Layer of Emotional Burden for Patients Discoveries in Race-Related Breast Cancer Biomarkers May Improve Precision Treatments What Is HER-2-Low Breast Cancer? What Oncology Nurses Need to Know About Supporting AYAs With Cancer ONS books: Guide to Breast Cancer for Oncology Nurses Oncology Nursing Forum articles: An Integrative Review of the Role of Nurses in Fertility Preservation for Adolescents and Young Adults With Cancer Impact of Race and Area Deprivation on Triple-Negative Metastatic Breast Cancer Outcomes Relations of Mindfulness and Illness Acceptance With Psychosocial Functioning in Patients With Metastatic Breast Cancer and Caregivers ONS huddle cards: Altered Body Image Fertility Preservation Sexuality Other ONS resources: Breast Cancer Learning Library Fertility Preservation in Individuals With Cancer ONS Biomarker Database American Cancer Society's breast cancer resources American Society of Clinical Oncology continuing education resources Elephants and Tea Life, Interrupted Livestrong National Cancer Institute's breast cancer resources Stupid Cancer Young Survival Coalition To discuss the information in this episode with other oncology nurses, visit the ONS Communities.  To find resources for creating an ONS Podcast club in your chapter or nursing community, visit the ONS Podcast Library. To provide feedback or otherwise reach ONS about the podcast, email pubONSVoice@ons.org. Highlights From This Episode “When we use ‘adolescent and young adult,' we're really talking about age 19–35. Some groups will say 15–39, but right around that age. When we think about that age, think about what all could be going on during those ages. Late teenagers, they may be going off to college, they may be graduating high school, trying to set up their own life, trying to become independent from mom and dad. If you're talking about early to mid 30s, you could be talking about young parents, young career folks. So, just setting that into place makes you realize this can be a very tumultuous time for folks.” TS 2:06 “Unfortunately, this group tends to have more aggressive subtypes. We see more triple-negative in this group. We see more hormone-negative, HER2-positive in this group. Normal breast cancer cells should be stimulated by hormone. They are stimulated by hormones. So when you have a breast cancer cell that is not driven by hormones, it's much more difficult to treat. We tend to see more aggressiveness in these tumors. We also see a higher incidence in non-Caucasian folks in this age group compared to the older age groups.” TS 4:53 “I think we have gotten much better about understanding the importance of fertility preservation and getting reproductive endocrinologists in, sooner rather than later. If we have earlier-stage cancers and we have patients that want to try to preserve eggs, preserve fertility, sperm banking. … If you have that time to talk to them—maybe a 21-year-old—the primary thing on her mind is not how many children she wants to have one day. Maybe she's not even thought about having kids yet. It's still a question you need to [ask]. Do you want to try to preserve fertility? Do you want to try to harvest some eggs? That's a conversation that needs to be had and is very, very important for that age group.” TS 10:35 “One thing that helps is if you can get them [into] reputable support groups with people their own age that are going through what they're going through. Someone else that doesn't have hair, someone else that isn't going to make it to the big board meeting or isn't going to get the promotion this year because they've had to take a medical leave. Someone else that understands it differently.” TS 16:47 “In breast cancer, many of those biomarkers just get reflexed. And what I mean by reflexed is a breast cancer pathology comes through, or a breast cancer specimen comes through, and it just automatically gets tested for X, Y, Z. HER2 and of course ER/PR. Now we understand that we don't just need to know whether they're HER2 positive or HER2 negative. We need to know: What is the IHC score? And even if the IHC score is zero, is there any membrane staining? And then we need to know what's their ESR1, their PTEN, their AKT, their PIK3CA. Those are so important to know.” TS 18:11 “I think it's important to try to remember what our priorities were when we were in our 20s—what our priorities were when we were starting out as young mothers or starting out our career. Because that's where these folks are. … I can't imagine in the midst of college, when I'm trying to be independent, to suddenly have to be at home and rely on my mom to take me to my chemo appointment. … So I think one really important bias is to remember where they are in the developmental stages of life. They're not 40-something. They haven't lived X amount of life, and we need to take a step back and try to remember when we were their age, what was important to us? Where were our priorities at that point? And then hear them when they're telling us what's important to them.” TS 29:22 “From a female standpoint … we frequently throw these patients into menopause or have early menopausal symptoms, and I think we forget how devastating that can be. … They now are at higher risk for osteopenia or osteoporosis. … And then we tell people, ‘Be as normal as possible, get back and do those normal things.' Well, they're in a relationship, and they want to be intimate [but] suddenly having sexual intercourse is incredibly painful. Or if it's not painful, sometimes they've just lost pure interest in that. They don't feel confident about their body. All of those things need to be addressed because patients are trying to live each day as normally as possible.” TS 31:55 

BUFFALO, NY – August 15, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on August 13, 2025, titled “Clinical and analytical validation of MI Cancer Seek®, a companion diagnostic whole exome and whole transcriptome sequencing-based comprehensive molecular profiling assay.” In this study, first authors Valeriy Domenyuk and Kasey Benson, along with corresponding author David Spetzler from Caris Life Sciences in Irving, Texas, introduce MI Cancer Seek, an FDA-approved test designed to deliver comprehensive tumor profiling. MI Cancer Seek demonstrated strong concordance with other FDA-approved companion diagnostics and serves as a powerful tool to guide treatment decisions in both adult and pediatric cancer patients. Cancer remains one of the most complex and diverse diseases to treat. With many targeted therapies currently FDA-approved, selecting the right one for a specific patient requires detailed genetic insights. MI Cancer Seek addresses this need by analyzing both DNA and RNA from a single tumor sample. The tool identifies key biomarkers linked to FDA-approved treatments for several major cancers, including breast, lung, colon, melanoma, and endometrial cancers. One of the most significant strengths of MI Cancer Seek is its ability to deliver accurate and reliable results from minimal tissue input (50 ng). Even when analyzing formalin-fixed paraffin-embedded samples, which are widely used but often degraded, the test maintained high levels of accuracy. It successfully detected important genetic alterations such as PIK3CA, EGFR, BRAF, and KRAS/NRAS mutations and measured tumor mutational burden (TMB) and microsatellite instability (MSI), both of which are key indicators for immunotherapy response. In clinical comparisons, the test achieved over 97% agreement with other FDA-approved diagnostic tools, confirming its reliability in detecting critical biomarkers. Notably, it showed near-perfect accuracy in identifying MSI status in colorectal and endometrial cancers. The researchers also demonstrated that the test maintains precision across different lab conditions and varying DNA input levels, confirming its robustness for routine clinical use. Beyond its role as a companion diagnostic, MI Cancer Seek incorporates additional features developed under its predecessor, MI Tumor Seek Hybrid. These include detection of homologous recombination deficiency, structural variants, and cancer-related viruses. It also includes advanced tools such as the Genomic Probability Score for identifying the tissue of origin in cancers of unknown primary, as well as a gene signature to guide first-line chemotherapy in colorectal cancer. “One limitation to be considered is the low PPA for ERBB2 CNA detection.” By offering deeper genetic insights from a single, small sample, MI Cancer Seek has the potential to streamline diagnostics, reduce testing costs, and connect patients to effective therapies more quickly. As precision medicine continues to expand, this assay stands out as a comprehensive and efficient solution for meeting the evolving needs of modern oncology. DOI - https://doi.org/10.18632/oncotarget.28761 Correspondence to - David Spetzler - dspetzler@carisls.com Video short - https://www.youtube.com/watch?v=D4hd2FxCYY8 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

Host: Charles Turck, PharmD, BCPS, BCCCP Guest: Neil M. Iyengar, MD Due to their wild-type inhibition, first-generation PIK3CA inhibitors for HR+/HER2- advanced breast cancer were limited by significant toxicities, including hyperglycemia, rash, and diarrhea. But now, mutation-specific PIK3CA inhibitors could help improve tolerability and adherence as well as simplify dosing strategies—all while maintaining efficacy. To learn more about the efficacy and safety of current and emerging PIK3CA-targeted therapies, Dr. Charles Turck speaks with Dr. Neil Iyengar, Co-Director of the Breast Oncology Program and Director of Cancer Survivorship Service at Winship Cancer Institute at Emory University.

Host: Charles Turck, PharmD, BCPS, BCCCP Guest: Neil M. Iyengar, MD Due to their wild-type inhibition, first-generation PIK3CA inhibitors for HR+/HER2- advanced breast cancer were limited by significant toxicities, including hyperglycemia, rash, and diarrhea. But now, mutation-specific PIK3CA inhibitors could help improve tolerability and adherence as well as simplify dosing strategies—all while maintaining efficacy. To learn more about the efficacy and safety of current and emerging PIK3CA-targeted therapies, Dr. Charles Turck speaks with Dr. Neil Iyengar, Co-Director of the Breast Oncology Program and Director of Cancer Survivorship Service at Winship Cancer Institute at Emory University.

In this episode, Kevin Kalinsky, MD, MS, FASCO, and Sara M. Tolaney, MD, MPH, discuss the most clinically relevant data in breast cancer presented at the 2025 ASCO Annual Meeting, including: DESTINY-Breast09: phase III trial of trastuzumab deruxtecan with or without pertuzumab vs THP as first-line treatment of HER2-positive advanced/metastatic breast cancerASCENT-04/KEYNOTE-D19: phase III trial of first-line sacituzumab govitecan plus pembrolizumab vs chemotherapy plus pembrolizumab in PD-L1–positive advanced TNBCSERENA-6: phase III trial of ctDNA-guided switch to camizestrant plus CDK4/6i vs continued AI plus CDK4/6i following ESR1 mutation emergence in HR-positive/HER2-negative advanced breast cancerINAVO120: OS from phase III study of first-line inavolisib/PBO plus palbociclib plus fulvestrant in PIK3CA-mutated, HR-positive/HER2-negative, endocrine-resistant advanced breast cancerPresenters:Kevin Kalinsky, MD, MS, FASCO​Professor of Medicine​Louisa and Rand Glenn Family Chair in Breast Cancer Research​Winship Cancer Institute​Emory UniversityAtlanta, Georgia​Sara M. Tolaney, MD, MPH​Chief, Breast Oncology​Dana-Farber Cancer Institute​Associate Professor of Medicine​Harvard Medical School​Boston, Massachusetts​Content based on an online CME program supported by independent educational grants from AstraZeneca, Daiichi Sankyo, Inc, Gilead Sciences, Inc., Lilly, Novartis Pharmaceuticals Corporation, and Stemline Therapeutics, Inc.Link to full program: https://bit.ly/4lFS4BC

Welcome to the Oncology Brothers podcast! In this episode, Drs. Rahul and Rohit Gosain are joined by Dr. Erika Hamilton from the Sarah Cannon Research Institute to discuss the latest breakthroughs in breast cancer presented at the ASCO 2025 annual meeting. We dived into five key abstracts that could change the landscape of breast cancer treatment: 1.⁠ INAVO120: observed overall survival data with the combination of inavolisib, with palbociclib and fulvestrant for patients with PIK3CA mutated hormone receptor-positive, HER2-negative advanced breast cancer. 2.⁠ ⁠SERENA-6: camizestrant use in patients with emerging ESR1 mutations using ctDNA, showed significant improvement in progression-free survival. 3.⁠ ⁠VERITAC-2: vepdegestrant showed superior progression-free survival compared to fulvestrant, particularly in ESR1 mutated patients. 4.⁠ ⁠DESTINY-Breast09: significant improvement in progression-free survival with TDXd plus pertuzumab in frontline HER2-positive metastatic breast cancer, challenging the traditional CLEOPATRA regimen THP. 5.⁠ ⁠ASCENT-04: promising results of sacituzumab combined with pembrolizumab in PD-L1 positive triple-negative breast cancer. Join us for an insightful discussion on these practice changing/informing studies and their implications for clinical practice.  YouTube: https://youtu.be/5XvrOn2p0jc Follow us on social media: •⁠  ⁠X/Twitter: https://twitter.com/oncbrothers •⁠  ⁠Instagram: https://www.instagram.com/oncbrothers •⁠  Website: https://oncbrothers.com/ Don't forget to like, subscribe, and check out our other episodes for more updates on treatment algorithms, recent approvals, and conference highlights!

In this episode, we unpack game-changing insights from ASCO 2025 with a spotlight on breast cancer. Joining us is Dr. Adam Brufsky, a trailblazing oncologist and professor at the University of Pittsburgh, with 30 years of experience, whose expertise has helped shape the direction of treatment. Trials discussed include the SERENA-6 trial, which examines camizestrant plus CDK4/6 inhibitors in HR-positive, ESR1 mutation breast cancer; the DESTINY-Breast09 trial, highlighting trastuzumab deruxtecan in combination with pertuzumab; and the INAVO120 trial, revealing inavolisib's triplet therapy response in PIK3CA-mutated, HR-positive, HER2-negative disease. Join us for a deep dive into these game-changing findings and their impact on patient care.Studies discussed in the episode:SERENA-6DESTINY BREAST 09INAVO 120For more episodes, resources and blog posts, visit www.inquisitiveonc.comPlease find us on Twitter @InquisitiveOnc!If you want us to look at a specific trial or subject, email us at inquisitiveonc@gmail.comArt courtesy of Taryn SilverMusic courtesy of AlisiaBeats: https://pixabay.com/users/alisiabeats-39461785/Disclaimer: This podcast is for educational purposes only. If you are unwell, seek medical advice.Oncology for the Inquisitive Mind is recorded with the support of education grants from our foundation partners Pfizer, Gilead Pharmaceuticals and Merck Pharmaceuticals. Our partners have access to the episode at the same time you do and have no editorial control over the content. Hosted on Acast. See acast.com/privacy for more information.

Featuring an interview with Dr Rinath M Jesselsohn, including the following topics: Imlunestrant with or without abemaciclib in advanced breast cancer: Results of the Phase III EMBER-3 trial (0:00) Jhaveri KL et al. Imlunestrant with or without abemaciclib in advanced breast cancer. N Engl J Med 2025;392(12):1189-202. Abstract  Jhaveri KL et al. Imlunestrant, an oral selective estrogen receptor degrader (SERD), as monotherapy & combined with abemaciclib, for patients with ER+, HER2- advanced breast cancer (ABC), pretreated with endocrine therapy (ET): Results of the Phase 3 EMBER-3 trial. San Antonio Breast Cancer Symposium 2024;Abstract GS1-01. Comprehensive genomic profiling of ESR1, PIK3CA, AKT1 and PTEN in HR-positive, HER2-negative metastatic breast cancer: Prevalence along treatment course and predictive value for endocrine therapy resistance in real-world practice (7:00) Bhave MA et al. Comprehensive genomic profiling of ESR1, PIK3CA, AKT1, and PTEN in HR(+)HER2(-) metastatic breast cancer: Prevalence along treatment course and predictive value for endocrine therapy resistance in real-world practice. Breast Cancer Res Treat 2024;207(3):599-609. Abstract Camizestrant, a next-generation oral selective estrogen receptor degrader (SERD), versus fulvestrant for postmenopausal women with estrogen receptor-positive, HER2-negative advanced breast cancer (SERENA-2): A multi-dose, open-label, randomized, Phase II trial (10:25) Oliveira M et al. Camizestrant, a next-generation oral SERD, versus fulvestrant in post-menopausal women with oestrogen receptor-positive, HER2-negative advanced breast cancer (SERENA-2): A multi-dose, open-label, randomised, phase 2 trial. Lancet Oncol 2024;25(11):1424-39. Abstract Latest on SERDs: An education session at San Antonio Breast Cancer Symposium 2024 (13:57) Jeselsohn RM. Latest on selective estrogen receptor degraders (SERDs). San Antonio Breast Cancer Symposium 2024;Education Session 5. CME information and select publications

Featuring an interview with Dr Sara A Hurvitz, including the following topics: Role of endocrine therapy in the management of HER2-positive breast cancer; implications of the Phase III PATINA study (0:00) Case: A woman in her mid 60s with node-negative, HR-positive, HER2-negative localized breast cancer and a Recurrence Score® of 28 (8:38) Available data guiding the selection of an adjuvant CDK4/6 inhibitor (12:49) Selection of a CDK4/6 inhibitor in the metastatic setting (23:16) Available therapies for patients with HR-positive metastatic breast cancer (mBC) and PIK3CA mutations; implications of the Phase III INAVO120 study (29:17) Case: A woman in her early 60s with HR-positive, HER2-negative mBC with short duration of benefit from a first-line CDK4/6 inhibitor and an aromatase inhibitor (AI) and coexisting PIK3CA and ESR1 mutations (37:11) Available data with approved and investigational oral SERDs (selective estrogen receptor degraders) (43:23) Case: A woman in her early 70s with HR-positive, HER2-negative mBC and an ESR1 mutation detected on disease progression after durable responses to first-line endocrine therapy and second-line CDK4/6 inhibitor with an AI (51:38) Selection of therapy for patients with HR-positive mBC and coexisting targetable genetic mutations (53:11) Case: A woman in her late 50s with HR-positive, HER2-negative mBC and an ESR1 mutation detected on disease progression after first-line CDK4/6 inhibitor with an AI (1:00:17) CME information and select publications

Send us a textWelcome to The Oncology Journal Club Podcast Series 3! Proudly produced by The Oncology NetworkThree respected oncologists dive deep into the most significant research presented at ASCO GI 2025, bringing you practice-changing insights amidst a backdrop of political uncertainty affecting medical research.Professor Chris Karapetis joins hosts Professor Craig Underhill and Professor Christopher Jackson to unpack ground-breaking colorectal cancer studies that are reshaping treatment paradigms. The conversation explores how targeted therapies are dramatically improving survival rates, with the DEEPER study demonstrating cetuximab's superiority over bevacizumab for left-sided RAS wild-type disease, achieving an impressive 50-month median survival when combined with chemotherapy.The experts dissect the BREAKWATER trial, which shows promising benefits of combining encorafenib and cetuximab with chemotherapy for notoriously aggressive BRAF-mutant colorectal cancer. This combination achieved a 61% response rate versus 40% with standard care, with responses lasting significantly longer – representing a potential new standard of care for this difficult-to-treat subgroup.Perhaps most surprisingly, our panel discusses how an inexpensive, familiar medication – aspirin – could reduce colorectal cancer recurrence by 40% in patients with PIK3CA mutations according to the ALASCCA study. This finding highlights how molecular profiling is becoming essential across treatment stages, not just for expensive targeted therapies but also for optimising use of accessible interventions.The discussion extends to exciting developments in pancreatic cancer with a novel pan-RAS inhibitor showing meaningful activity, and advancements in immunotherapy for MSI-high colorectal cancer, confirming combination therapy's superiority. For gastrointestinal oncologists navigating an increasingly complex treatment landscape, this episode offers crucial insights to optimise patient outcomes through precise, personalised approaches.Subscribe to The Oncology Newsletter for regular updates on the latest cancer research and join our community at oncologynetwork.com.au.The Oncology Podcast - An Australian Oncology Perspective

Dr Kaklamani discusses the mechanism of action of inavolisib, the importance of the addition of this agent to the HR-positive metastatic breast cancer treatment paradigm, and considerations for early biomarker testing in patients with breast cancer. 

Breast cancer treatment today is becoming more personalized and more precise. Precision medicine is rapidly expanding the options patients have for treating their cancer while helping them maintain a desired quality of life. A common mutation in breast cancer called PIK3CA affects more than 1 in 3 people with breast cancer, making it harder to treat. This mutation often leads to worse outcomes for these patients compared to others. Scientists are now developing new treatments that target this mutation specifically, aiming to reduce side effects and improve treatment outcomes, such as shrinking tumors or preventing disease progression. Today, we are speaking with Dr. Sarah Sammons of Dana-Farber Cancer Institute to explore the exciting new possibilities brought by personalized medicine, including whether it can help slow disease progression and how it can it improve patients' abilities to potentially live more active and productive lives while on treatment.

In today's episode, supported by Genentech, we had the pleasure of speaking with Komal Jhaveri, MD, FACP, about the clinical use of inavolisib (Itovebi) for patients with hormone receptor (HR)–positive, PIK3CA-mutated, locally advanced or metastatic breast cancer. Dr Jhaveri is section head of the Endocrine Therapy Research Program, clinical director of the Early Drug Development Service, and the Patricia and James Cayne Chair for Junior Faculty at Memorial Sloan Kettering Cancer Center in New York, New York. In our exclusive interview, Dr Jhaveri discussed the importance of having a PI3K inhibitor available for the treatment of patients with HR-positive metastatic breast cancer, advice for managing inavolisib-related adverse effects, and best practices for early biomarker testing in patients with breast cancer.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/VMG865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until February 5, 2026.Targeting PIK3CA/AKT1/PTEN and Other Alterations in HR+, HER2- MBC: Navigating the Evidence and Guidance for Use In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an independent educational grant from AstraZeneca.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/VMG865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until February 5, 2026.Targeting PIK3CA/AKT1/PTEN and Other Alterations in HR+, HER2- MBC: Navigating the Evidence and Guidance for Use In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an independent educational grant from AstraZeneca.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/VMG865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until February 5, 2026.Targeting PIK3CA/AKT1/PTEN and Other Alterations in HR+, HER2- MBC: Navigating the Evidence and Guidance for Use In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an independent educational grant from AstraZeneca.Disclosure information is available at the beginning of the video presentation.

BUFFALO, NY - January 22, 2025 – A new #review was #published in Oncotarget's Volume 16 on January 20, 2025, titled “Evolving concepts in HER2-low breast cancer: Genomic insights, definitions, and treatment paradigms." Researchers Whitney L. Hensing, Emily L. Podany, James J. Sears, Shaili Tapiavala, and Andrew A. Davis from the University of Missouri-KC School of Medicine and Washington University in St. Louis School of Medicine explore HER2-low breast cancer, a recently recognized type of breast cancer that is changing the way clinicians should approach treatment. The review explains what makes HER2-low breast cancer different and highlights new treatment options that are helping patients. “Breast cancer, which has been historically classified as HER2-positive versus HER2-negative, is currently facing a paradigm shift in both the definition of HER2 status and in the existing treatment algorithms.” Breast cancer is usually classified into two main types based on the HER2 protein: HER2-positive or HER2-negative. HER2-low breast cancer falls somewhere in between. Thanks to new targeted treatments, such as a drug called trastuzumab deruxtecan, patients with HER2-low breast cancer now have more options and better chances of responding to treatment. The review looks at recent studies on the genetics of HER2-low breast cancer. Researchers found that these tumors are often hormone receptor (HR)-positive, meaning they respond to hormones like estrogen. Some tumors also carry a common genetic change called a PIK3CA mutation, which could affect how well treatments work. However, experts say HER2-low breast cancer is not a completely separate breast cancer type but rather an opportunity for more personalized treatment. “Despite evidence from existing literature that HER2-low breast cancer does not represent a distinct biologic and prognostic subtype, the introduction of HER2-low expression as a therapeutic target has expanded patient eligibility for a potent class of anti-HER2 drugs, HER2-directed ADCs, with potential for significant efficacy.” Despite these advances, diagnosing HER2-low breast cancer can still be difficult. Current testing methods are not always accurate, and different laboratories may get different results. The review calls for better detection methods to make sure patients who can benefit from these new treatments are correctly identified. With cancer treatments becoming more personalized, the review also explains how clinicians can fit HER2-low treatments into existing guidelines to help patients. The success of targeted therapies is changing how breast cancer is treated, especially for patients whose cancer has metastasized. In conclusion, experts believe ongoing research will continue to improve the way HER2-low breast cancer is diagnosed and treated. However, they stress the need for better detection methods and continued exploration of new therapies to help patients get the best possible care. DOI - https://doi.org/10.18632/oncotarget.28680 Correspondence to - Andrew A. Davis - aadavis@wustl.edu About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

Welcome to another episode of the Oncology Brothers podcast! In this episode, hosts Drs. Rahul and Rohit Gosain dive deep into the recent FDA approval of Inavolisib for metastatic hormone receptor-positive breast cancer, based on the groundbreaking INAVO120 study. Join us as we chat with Dr. Komal Jhaveri, a medical oncologist and senior author of the study from Memorial Sloan Kettering Cancer Center. We explored the study design, key findings, and the implications of this new treatment option for patients with PIK3CA mutations. Key topics discussed include: •⁠  ⁠Overview of the INAVO120 study and its significance •⁠  ⁠The unique patient population targeted in the study •⁠  ⁠Key findings, including the impressive improvement in progression-free survival (PFS) •⁠  ⁠Side effects and management strategies for patients •⁠  ⁠The importance of genetic testing in treatment decisions Whether you're a healthcare professional or someone interested in the latest advancements in oncology, this episode provides valuable insights into the evolving landscape of breast cancer treatment. Don't forget to like, subscribe, and hit the notification bell for more updates from the Oncology Brothers! #OncologyBrothers #BreastCancer #ENAVOLacib #PIK3CA #CancerResearch #MedicalPodcast #Oncology Website: http://www.oncbrothers.com/ X/Twitter: https://twitter.com/oncbrothers Contact us at info@oncbrothers.com

A new PIK3Ca inhibitor is approved for breast cancer.

Join us for an informative discussion about PIK3CA testing and treatment with Dr. Neil Iyengar