Breast Cancer Experts Bookmark Top Abstracts to Watch at the 2025 ASCO Annual Meeting

Alexis LeVee, MD

As we gear up for the 2025 ASCO Annual Meeting, OncLive® asked breast cancer experts to highlight the research and discussions they’re most excited to see presented at the meeting.

We gathered exclusive insights from:

• Yara Abdou, MD, an assistant professor of medicine in the Division of Oncology in the Department of Medicine at the University of North Carolina (UNC) School of Medicine-Chapel Hill; as well as the Breast Cancer Clinical Trial Program leader at the UNC Lineberger Comprehensive Cancer Center
• Adam M, Brufsky, MD, PhD, a professor of medicine and associate chief of the Division of Hematology/Oncology at the University of Pittsburgh School of Medicine; as well as co-director of the Comprehensive Breast Cancer Center, associate director of Clinical Investigation, and medical director of the Magee-Women’s Cancer Program at the University of Pittsburgh Medical Center Hillman Cancer Center in Pennsylvania
• Neil M. Iyengar, MD, an associate attending physician at Memorial Sloan Kettering Cancer Center in New York, New York
• Alexis LeVee, MD, chief fellow of Hematology & Medical Oncology at City of Hope in Duarte, California
• Bora Lim, MD, an associate professor and chief of the Section of Translational Breast Cancer Research in the Department of Breast Medical Oncology in the Division of Cancer Medicine, as well as director of Translational Research in the Department of The Morgan Welch IBC Research Program and Clinic in the Division of Cancer Medicine at the University of Texas MD Anderson Cancer Center in Houston
• Jane L. Meisel, MD, a professor and co-director of Breast Medical Oncology in the Department of Hematology and Medical Oncology, as well as a professor in the Department of Gynecology & Obstetrics at Emory University School of Medicine, Winship Cancer Institute, in Atlanta, Georgia
• Barbara Pistilli, MD, chair of the Breast Cancer Unit at Gustave Roussy in Villejuif, France
• Sarah Sammons, MD, the associate director of the Metastatic Breast Cancer Program at Dana-Farber Cancer Institute (DFCI) in Boston, Massachusetts; as well as an assistant professor of medicine at Harvard Medical School
• Paolo Tarantino, MD, PhD, a clinical fellow at DFCI
• Sara M. Tolaney, MD, MPH, chief of the Division of Breast Oncology and the associate director of the Susan F. Smith Center for Women’s Cancers at DFCI; as well as an assistant professor of medicine at Harvard Medical School

From phase 3 data that have been teased in the news to abstracts that will add to discussions regarding shifting standards of care (SOCs), here’s what made these experts’ lists:

Abstract 1015: Treatment rechallenge after trastuzumab-deruxtecan–related interstitial lung disease: A multi-institution cohort study.

Session time: May 30, 2:45-4:15pm CDT

LeVee: There’s a study evaluating rechallenge of fam-trastuzumab deruxtecan-nxki [T-DXd; Enhertu] after grade 1 interstitial lung disease [ILD] and how patients respond after being rechallenged. A lot of these data will be interesting to try to improve outcomes for patients, both by minimizing toxicity and by better personalizing our therapies.

Abdou: This study is exciting because T-DXd is one of the most powerful drugs in our arsenal—and ILD has been its biggest barrier. Understanding whether we can safely rechallenge patients opens the door to reclaiming a highly effective therapy for those who need it most.

Abstract 1019: Sacituzumab tirumotecan (sac-TMT) as first-line treatment for unresectable locally advanced/metastatic triple-negative breast cancer (a/mTNBC): Initial results from the phase II OptiTROP-Breast05 study.

Session time: May 30, 2:45-4:15pm CDT

Lim: [Sacituzumab tirumotecan (formerly SKB264/MK-2870)]—a cousin of sacituzumab govitecan-hziy [Trodelvy]—is interesting, [and this trial] provides new opportunity to compare and learn about differences between antibody-drug conjugates [ADCs].

Abstract 1007: Phase III of oral paclitaxel (DHP107) vs intravenous paclitaxel in HER2-negative recurrent or metastatic breast cancer (mBC): Primary analysis of a multinational optimal trial (NCT03315364).

Session time: May 31, 1:15-4:15pm CDT

Lim: I have been interested in various forms of oral paclitaxel, and this [trial] will certainly open a new era of oral paclitaxel, if positive.

Abstract LBA1000: Vepdegestrant, a PROTAC estrogen receptor (ER) degrader, vs fulvestrant in ER-positive/human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer: Results of the global, randomized, phase 3 VERITAC-2 study.

Session time: May 31, 1:15-4:15pm CDT

Lim: It will be interesting to see if the PROTAC will perform as well as fulvestrant [(Faslodex) in this population].

Meisel: The phase 3 VERITAC-2 trial [NCT05654623] is a study investigating vepdegestrant, an estrogen receptor [ER] degrader…vs fulvestrant in patients who received 1 or 2 prior lines of endocrine therapy. This will be the first presentation of results for this study, [and we will see] how vepdegestrant compares with fulvestrant in terms of progression-free survival [PFS] in these patients. If this is a positive study, which we'll find out about at ASCO, it’s possible that [vepdegestrant] could become a new option for patients with ER-positive metastatic disease. There's so much excitement in this area about how to extend endocrine sensitivity, especially with agents that are well tolerated and effective. Seeing the results of this trial will maybe help push us further in that direction.

Abstract LBA109: Sacituzumab govitecan (SG) + pembrolizumab (pembro) vs chemotherapy (chemo) + pembro in previously untreated PD-L1–positive advanced triple-negative breast cancer (TNBC): Primary results from the randomized phase 3 ASCENT-04/KEYNOTE-D19 study.

Session time: May 31, 1:15-4:15pm CDT

Sara M. Tolaney, MD, MPH

Tolaney: [The phase 3] ASCENT-04 trial [NCT05382286] is investigating the combination of sacituzumab govitecan-hziy [Trodelvy]—a TROP-2–directed antibody-drug conjugate [ADC]—in combination with pembrolizumab [Keytruda] compared with chemotherapy of physician’s choice plus pembrolizumab for patients who have metastatic triple-negative breast cancer that’s also PD-L1 positive. [These patients are] getting treated in the first-line setting. We’ve seen a news release from this trial, which has told us that sacituzumab govitecan plus pembrolizumab did lead to an improvement in progression-free survival [PFS] compared with chemotherapy plus pembrolizumab.1 We’re hoping that will become a new first-line option for our patients. We’ve desperately been wanting to improve outcomes for metastatic triple-negative disease, so this could be a really nice improvement for patients in the early-[line] setting.

Iyengar: This study is going to be interesting for a couple reasons. First, we know that that triple-negative breast cancer [TNBC] is an aggressive type of breast cancer, so the therapies we're using in the up-front setting can set the tone for how the cancer will be controlled moving forward. I view that first-line treatment selection to be critical in terms of long-term outcomes for patients. Immunotherapy has improved outcomes for patients with PD-L1–positive TNBC in the metastatic setting, but it can be a challenging regimen. Chemotherapy plus pembrolizumab is associated with several toxicities, both immune-related toxicities, as well as chemotherapy-related toxicities.

Sacituzumab govitecan is an ADC that is also [associated with] toxicities, but it is generally better tolerated than standard chemotherapy. If we have a better tolerated and more effective regimen with sacituzumab govitecan plus pembrolizumab, that would be practice changing. I'm looking forward to seeing the data to see what the numbers look like, what the magnitude of benefit is, and [to keep] an eye out for the toxicities, because it would be a win for our patients if we can use a more effective regimen that is better tolerated in the first-line setting.

Lim: All my patients who are on this study are doing really well. I look forward to seeing the first waves of ADC plus immuno-oncology data in breast cancers.

Abdou: The ASCENT-04 study is a landmark moment—bringing ADCs like sacituzumab govitecan into the first-line setting is a bold leap forward for TNBC. It’s thrilling to see precision-engineered therapies replacing blunt chemotherapy as the new standard for the most aggressive breast cancers.

Meisel: This will be the first time that this study has reported out. Knowing how helpful sacituzumab govitecan is for metastatic TNBC in later lines of therapy makes people excited about the potential for using this [agent] closer to the first presentation of disease. And this could be [a treatment] that moves into the first-line setting if the study results are positive.

Pistilli: This study included patients with TNBC who had a [PD-L1] combined positive score score of at least 10, who today are likely to receive pembrolizumab plus chemotherapy as first-line treatment.1 This study is likely to change our practice in the near future in patients with TNBC, for whom we urgently need to have new, more effective treatment options.

Brufsky: This trial will likely be practice changing if the PFS [benefit] with sacituzumab govitecan/pembrolizumab exceeds [that with] the standard-of-care [SOC] therapy by a substantial and clinically significant amount.

Abstract LBA4: Camizestrant + CDK4/6 inhibitor (CDK4/6i) for the treatment of emergent ESR1 mutations during first-line (1L) endocrine-based therapy (ET) and ahead of disease progression in patients (pts) with HR+/HER2– advanced breast cancer (ABC): Phase 3, double-blind ctDNA-guided SERENA-6 trial.

Session time: June 1, 1:00-4:00pm CDT

Sarah Sammons, MD

Sammons: [The phase 3] SERENA-6 trial [NCT04964934] is exciting because it’s challenging the historic paradigm of how we manage metastatic breast cancer in general. In metastatic breast cancer, we treat patients with a regimen that we know to be the most successful based on clinical trials, and we wait to change their therapy until the disease has developed resistance enough to form new tumors on scans.

SERENA-6, for the first time in a phase 3 registrational capacity, is trying to intervene on the cancer cells before we see radiographic progression, when we see that [patients] are developing mutations of resistance in the blood. This trial is in patients with metastatic estrogen receptor [ER]–positive, HER2-negative breast cancer [who had received a] first-line aromatase inhibitor [AI] and a CDK4/6 inhibitor for at least 6 months [and had undergone] blood testing to look for the emergence of ESR1 mutations, which denote resistance to AIs. If those patients developed an ESR1 mutation and still did not have progression on their scans, then they were randomly assigned to either continue their CDK4/6 inhibitor with the AI, which would be the SOC in current clinical practice, or—based on molecular emergence of an ESR1 mutation—switch early to camizestrant, which is an oral selective estrogen receptor degrader that targets ESR1. [in combination with a CDK4/6 inhibitor].

Can we prolong the PFS if we intervene early in the resistance [development], rather than waiting for [patients] to have disease progression on scans? PFS is the primary end point. We’re all going to want to make sure that not only PFS, but also time to second progression and potentially overall survival [OS], are improved by early switch to this type of strategy. For my patients, one of the best quality of life times that they have in their disease is their time receiving a CDK4/6 inhibitor. I’m hoping to extend the amount of time that patients can stay on their CDK4/6 inhibitor for as long as possible, because after that, we move into cytotoxic and targeted therapies that have more toxicity. [SERENA-6], if positive, is going to open the way for new trial designs and is really of value.

Paolo Tarantino, MD, PhD

Tarantino: There’s going to be a very cool breast cancer abstract in the plenary session. We [typically] treat patients [with ER-positive breast cancer] in the first-line setting with CDK4/6 inhibitors, and then in the second-line setting with other agents after progression. However, SERENA-6 uses a different approach, one that was derived from a prior phase 3 trial called PADA-1 [NCT03079011], where, instead of waiting for disease progression before moving to second-line treatment for hormone receptor [HR]–positive metastatic breast cancer, you switch treatment upon emergence on circulating tumor DNA [ctDNA] of ESR1 mutations. Approximately 40% of patients have an emergence of ESR1 mutations during first-line treatment.

We’ll see more data from PADA-1 at the 2025 ESMO Breast Cancer Congress before ASCO, but in the SERENA-6 trial, which was announced to be positive, apparently switching to camizestrant upon emergence of an ESR1 mutation, maintaining treatment with a CDK4/6 inhibitor, led to a significant PFS advantage.2 It will be very important to look at the magnitude of benefit from this trial, because we want to understand whether a strategy of monitoring patients with ctDNA assays every 3 months in the absence of progression is advantageous in long-term outcomes, [such as] OS. It will be an important moment to see the benefit of a new drug, camizestrant, but also to understand this new paradigm of following patients with ctDNA [testing] in the absence of progression. [These data could help us] see if switching treatment is advantageous for the most prevalent category of patients we see in the clinic, which is those with metastatic HR-positive breast cancer.

Iyengar: The key question with trials with this type of design is: If there's a PFS benefit with this approach, is that simply because of lead time bias, or are we truly altering and improving long-term outcomes like OS by changing therapy based upon the emergence of a resistance mutation? I'll be looking at these data with an eye to see whether there is a contribution of lead time bias. If we see a significant magnitude of PFS benefit, I think that makes lead time bias less likely. Ultimately, we will need long-term data like OS, which we received from PADA-1 before SERENA-6, to determine whether this approach of changing therapy based on emerging resistance mutations is a more effective approach than waiting for radiographic or clinical progression.

Abdou: The SERENA-6 trial is a powerful glimpse into the future of precision oncology, where we don’t just react to cancer progression, we anticipate it. Using ctDNA to guide early intervention with camizestrant represents a bold, modern shift toward truly personalized, proactive care in HR-positive/HER2-negative breast cancer.

Meisel: This is a trial asking 2 important questions. Can we detect ESR1 mutations early in patients receiving first-line therapy for metastatic ER-positive breast cancer [who are] doing well? And if we find those ESR1 mutations, can we change the course of [the disease] trajectory by switching treatment prior to seeing progression on scans? This is the first time that these results will be presented, and [they] will begin to show us [whether] there is value to checking serial ctDNA in patients who are doing well on first-line therapy. Then, if we find [a mutation], is it appropriate to switch treatment before we see progression of disease on scans? [We are], for the first time, evaluating a molecular mechanism of detecting recurrence and intervening in a patient’s treatment course. It will be interesting to see what the results of this study show and to see if they could change treatment.

Brufsky: If there is a substantial and clinically significant improvement in PFS with this strategy of change to an oral selective estrogen receptor degrader before clinical progression, this will be the first demonstration [in any solid tumor] that treatment on the basis of molecular progression results in a clinically significant positive outcome. It will potentially be practice changing.

Abstract LBA1008: Trastuzumab deruxtecan (T-DXd) + pertuzumab (P) vs taxane + trastuzumab + pertuzumab (THP) for first-line (1L) treatment of patients (pts) with human epidermal growth factor receptor 2–positive (HER2+) advanced/metastatic breast cancer (a/mBC): Interim results from DESTINY-Breast09.

Session time: June 2, 7:30-8:00am CDT

Sammons: We are very excited to finally see the results of [the phase 3] DESTINY-Breast09 trial [NCT04784715], which is challenging the historical [SOC] first-line therapy in HER2-positive metastatic breast cancer that we’ve been using for over a decade now, which is a taxane with trastuzumab [Herceptin] and pertuzumab [Perjeta; THP]. DESTINY-Breast09 is a phase 3 trial that is investigating first-line therapy for these patients with 3 different arms: T-DXd, T-DXd with pertuzumab, or the control arm, which is the historical SOC of THP.

This trial is reportedly positive [according to] a news release, but we really need to see the results.3 They will lead to a lot of open questions in this patient population as to whether T-DXd with or without pertuzumab is superior in terms of PFS, which is the primary endpoint. How long are patients staying on this drug? In this trial, patients receive T-DXd indefinitely until progression or toxicity. There are open questions as to how long we need to continue T-DXd, how well our patients will tolerate T-DXd, and whether it’s truly a superior first-line therapy. Another [finding] I am very interested in seeing is whether we could potentially even consider curing more patients with HER2-positive metastatic breast cancer if we use more effective first-line therapies.

Tolaney: We’ve already seen a news release from this trial, which has told us that at the time of an interim analysis, the combination of T-DXd plus pertuzumab led to a significant improvement in PFS. We’re all excited to see whether that could become a new SOC option for our patients.

Iyengar: It will be important to dissect these data, because the current SOC, the phase 3 CLEOPATRA trial [NCT00567190] regimen, [is one] we have been using for a long time. We have long-term follow-up on the CLEOPATRA data. T-DXd is an effective treatment for HER2-positive and HER2-low breast cancer. The main question I'll have in my mind when reviewing the DESTINY-Breast09 data is: What is the magnitude of benefit [with T-DXd plus pertuzumab] over THP, particularly in terms of duration of response and PFS? This is an interim report, so we won't have long-term data to compare with [those from] CLEOPATRA.

The challenge in integrating the DESTINY-Breast09 data—if we will want to integrate [them]—is that the CLEOPATRA regimen offers a maintenance setting where we can withdraw the chemotherapy if a patient has a favorable response and maintain that response with just the antibody therapy, trastuzumab and pertuzumab. We've seen results from the phase 3 PATINA trial [NCT02947685], which indicates that adding the CDK4/6 inhibitor palbociclib [Ibrance] to hormone therapy during that maintenance period further extends PFS.

From a QOL standpoint, it is attractive to start with an induction period of chemotherapy based on the CLEOPATRA trial, maintain the response—if it's a good response—with the anti-HER2 antibodies trastuzumab and pertuzumab, and add in hormone therapy and palbociclib. DESTINY-Breast09 was designed like CLEOPATRA, so a maintenance period was not included. The question will be: Is the magnitude of benefit in DESTINY-Breast09 large enough to replace the CLEOPATRA regimen in the first-line setting and forego that maintenance period, which has a high QOL associated with it? Or are we still going to be using the CLEOPATRA regimen in the first-line setting, so we can use that maintenance period, as we already know that T-DXd is effective in the second-line setting and beyond?

Meisel: T-DXd is an exciting drug. It was first shown to be effective as later-line, HER2- directed therapy for patients with metastatic HER2-positive breast cancer. Then it eventually moved up [to become] the second-line SOC for these patients and has since also been shown to be effective for patients with HER2-low and even HER2-ultralow metastatic disease. Lots of patients are benefiting from this drug, but DESTINY-Breast09 is asking the question: In patients who are truly HER2 positive, might [T-DXd] be even more useful than the current SOC for patients with a new diagnosis of metastatic disease? This trial investigating how T-DXd performs in the frontline setting is a study that everyone has been eagerly awaiting, because if this is a positive study, we may be able to move this drug into the frontline setting for patients with HER2-positive metastatic disease, thus changing the SOC.

Pistilli: This is a huge study that included 1157 patients across different countries in the world.3 This may change our clinical practice and the treatment algorithm for patients with HER2-positive advanced breast cancer. It is likely that we are going to advance treatment with T-DXd into the first-line setting. The question thereafter will be: Can we keep these patients on this treatment for the long term? One of the major issues we have to face is to understand the optimal maintenance therapy we can use in patients receiving T-DXd in the first-line setting who cannot continue the treatment until progression.

Brufsky: This trial will likely be practice changing if the PFS with T-DXd exceeds [that with] the SOC therapy by a substantial and clinically significant amount.

Prevention, Risk Reduction, and Genetics

Session time: June 2, 11:30am-2:30pm CDT

Iyengar: We'll see interesting data with regard to modifiable risk factors for breast and other cancers. We will see a couple of studies looking at various cancer risk factors, both hereditary and environmental, including obesity as a risk factor for developing breast and other cancers. We are going to see 2 studies that will be presented, looking at the use of weight loss therapy in patients both with and without diabetes, and their effect on breast cancer risk.

One of the studies, [abstract 10507], is based on a large dataset [with an] interesting trial design. The investigators emulated a clinical trial using an observational dataset to look at the effect of GLP-1 receptor agonists on the development of obesity-related cancers in patients with diabetes. That will add to the growing literature looking at the effect of these novel weight loss therapies on obesity-associated cancers. [Then, abstract 10508] is a target trial emulation study looking at the effect of GLP-1 receptor agonists on cancer risk. This includes patients with diabetes, as well as patients without diabetes who use the drugs purely for the weight loss indication.

These 2 studies are going to be particularly informative because we've only seen small datasets so far in the post-diagnosis setting [regarding] the degree of weight loss with GLP-1 agonists in patients diagnosed with cancer. In the risk setting, we've seen a couple observational studies looking at large national databases that have shown that the use of weight loss drugs—particularly GLP-1 agonists—is associated with a lower incidence of developing obesity-associated cancers. However, those studies have really been isolated to patients with diabetes and patients who've been prescribed these drugs for diabetes treatment. A big question is: Now that the GLP-1 receptor agonists have an indication for weight loss independent of diabetes and are being used in patients without diabetes, do the drugs still have an effect on lowering the risk of developing obesity-associated cancers?

There are at least 13 obesity-associated cancers, including breast cancer. If these drugs do lower the risk of [developing] these 13 cancers independent of diabetes, this would be a potentially effective prevention strategy. The next steps would be to validate these observational findings in a prospective manner, and then address a lot of the disparities that exist with regard to access to these drugs, the cost of these drugs, etc. However, the first step is really looking at the association of these drugs on cancer risk.

Abstract 501: Predicting pathologic complete response (pCR) from clinicopathologic variables and HER2DX genomic test in stage II/III HER2+ breast cancer treated with taxane, trastuzumab, and pertuzumab (THP): Secondary results from the EA1181/CompassHER2 pCR trial.

Session time: June 2, 3:00-6:00pm CDT

Tolaney: One trial I’ve been really looking forward to is the [phase 2] CompassHER2-pCR trial [NCT04266249]. For patients who get treated in the early-stage setting for HER2-positive disease, the standard, at least in the United States, is usually to give a THP for 6 cycles. However, that therapy is associated with significant toxicities, so we’ve always wondered: Could we just give a taxane with trastuzumab and pertuzumab for 12 weeks, and then if [the patients achieve] a pathologic complete response [pCR], just continue the trastuzumab/pertuzumab antibodies to complete a year? [We though that might be] sufficient therapy for them because they got a pCR. Smaller studies have shown us that THP can result in very good pCR rates, but [CompassHER2-pCR is a] large cooperative group trial that will be important to see. [The investigators are also examining] a novel biomarker, HER2DX, and associating it with the pCRs in this trial. It will be interesting to see whether the HER2DX assay does well in predicting pCR.

References

1. Trodelvy plus Keytruda demonstrates a statistically significant and clinically meaningful improvement in progression-free survival in patients with previously untreated PD-L1+ metastatic triple-negative breast cancer. News Release. Gilead. April 21, 2025. Accessed May 13, 2025. https://www.gilead.com/news/news-details/2025/trodelvy-plus-keytruda-demonstrates-a-statistically-significant-and-clinically-meaningful-improvement-in-progression-free-survival-in-patients-with-previously-untreated-pd-l1-metastatic-trip
2. Camizestrant demonstrated highly statistically significant and clinically meaningful improvement in progression-free survival in 1st-line advanced HR-positive breast cancer with an emergent ESR1 tumour mutation in SERENA-6 Phase III trial. News release. AstraZeneca. February 26, 2025. Accessed May 13, 2025. https://www.astrazeneca.com/media-centre/press-releases/2025/camizestrant-improved-pfs-in-1l-hr-breast-cancer.html
3. Enhertu plus pertuzumab demonstrated highly statistically significant and clinically meaningful improvement in progression-free survival vs. THP as 1st-line therapy for patients with HER2-positive metastatic breast cancer. News release. AstraZeneca. April 21, 2025. Accessed May 13, 2025. https://www.astrazeneca.com/media-centre/press-releases/2025/enhertu-combination-improved-pfs-in-1l-her-positive-mbc.html