The American Society of Clinical Oncology (ASCO) Annual Meeting, held in Chicago from May 30 to June 3, captured an abundance of breast cancer updates poised to reshape treatment paradigms.
From innovative drug strategies to personalized approaches, the buzz around the ASCO 2025 meeting promises significant advancements for patients. In tandem with CURE® and OncLive®, experts in the field offered their take on what they were most excited about to come out of the meeting.
Hormone receptor-positive breast cancer
For patients with hormone receptor-positive (HR+) breast cancer, the focus is on extending the effectiveness of endocrine therapies. Dr. Jane Meisel, from Emory University School of Medicine, highlighted the phase 3 VERITAC-2 study (Abstract LBA1000) investigating vepdegestrant, a new estrogen receptor (ER) degrader, against the current standard, fulvestrant. If positive, vepdegestrant could offer a new, well-tolerated and effective option to prolong endocrine sensitivity.
Perhaps the most talked-about abstract in HR+/HER2- breast cancer is the phase 3 SERENA-6 trial (Abstract LBA4), because it challenges the traditional approach of waiting for visible disease progression before changing therapy. Instead, SERENA-6 explores the strategy of switching treatment proactively when ESR1 mutations, which indicate resistance to common endocrine therapies, emerge in circulating tumor DNA (ctDNA) in the blood, even before progression is seen on scans. Dr. Sarah Sammons, from Dana-Farber Cancer Institute, emphasized that SERENA-6 is “challenging the historic paradigm of how we manage metastatic breast cancer.” Dr. Paolo Tarantino, also from Dana-Farber Cancer Institute, noted that the trial, already announced as positive, showed a significant progression-free survival (PFS) advantage by switching to camizestrant, an oral selective ER degrader, upon ESR1 mutation emergence while maintaining a CDK4/6 inhibitor. While the immediate PFS benefit is exciting, experts like Dr. Neil Iyengar of Memorial Sloan Kettering Cancer Center, caution that it’s crucial to assess if this translates to long-term benefits like overall survival (OS), and to rule out “lead time bias” – where earlier detection merely leads to an earlier switch in therapy without truly extending life. Regardless, Dr. Abdou believes SERENA-6 offers a “powerful glimpse into the future of precision oncology, where we don’t just react to cancer progression, we anticipate it,” representing a “bold, modern shift toward truly personalized, proactive care.” Dr. Adam Brufsky, from the University of Pittsburgh School of Medicine, added that if the PFS improvement is substantial, it would be the “first demonstration [in any solid tumor] that treatment on the basis of molecular progression results in a clinically significant positive outcome.”
Triple-negative breast cancer
For patients with aggressive triple-negative breast cancer (TNBC), the phase 3 ASCENT-04/KEYNOTE-D19 study (Abstract LBA109) is investigating the combination of Trodelvy (sacituzumab govitecan) with Keytruda (pembrolizumab) compared to chemotherapy plus Keytruda as a first-line treatment for PD-L1 positive metastatic TNBC. Dr. Sara Tolaney, Chief of the Division of Breast Oncology at Dana-Farber Cancer Institute, confirmed a news release indicating that the combination improved PFS. Dr. Iyengar highlighted the importance of first-line treatment in TNBC, an aggressive cancer, and noted that Trodelvy is generally better tolerated than standard chemotherapy. If this regimen proves both more effective and better tolerated, it would be “practice changing.” Dr. Bora Lim, from the University of Texas MD Anderson Cancer Center, whose patients on this study are “doing really well,” is eager to see the first wave of antibody drug conjugate plus immuno-oncology data in breast cancers. Dr. Barbara Pistilli, from Gustave Roussy, anticipates this study will “change our practice in the near future.”
HER2-positive breast cancer: Challenging the long-standing standard
The phase 3 DESTINY-Breast09 trial (Abstract LBA1008) may challenge the long-standing standard of care for first-line HER2-positive metastatic breast cancer: a taxane with trastuzumab (Herceptin) and Perjeta (pertuzumab) (THP). This trial compares Enhertu (trastuzumab-deruxtecan; T-DXd) in combination with Perjeta or the historical standard of care of THP. Dr. Sammons noted the full data will reveal whether Enhertu with or without Perjeta is truly superior in terms of PFS and how long patients can stay on the drug. Dr. Tolaney is also excited about the potential for this combination to become a new standard. Dr. Iyengar emphasized the need to dissect the data, particularly regarding the magnitude of benefit, given the extensive long-term follow-up available for the current THP regimen. He questioned whether the benefit of T-DXd would be substantial enough to replace THP, especially considering the quality-of-life benefits of the THP maintenance period. Regardless, Dr. Meisel anticipates this trial could “change the standard of care” if positive, moving Enhertu into the frontline setting for these patients. Dr. Pistilli believes this “huge study” will likely advance Enhertu into the first-line setting, raising new questions about long-term maintenance strategies.
Personalizing early-stage HER2-positive treatment
Finally, the phase 2 CompassHER2-pCR trial (Abstract 501) offered insights into personalizing treatment for early-stage HER2-positive breast cancer. Dr. Tolaney explained that the trial investigates whether a shorter course of THP followed by Herceptin/Perjeta alone could be sufficient for patients who achieve a pathologic complete response (pCR), thereby minimizing toxicities. The study also explores the novel HER2DX biomarker’s ability to predict pCR, paving the way for more tailored and potentially less toxic treatments for these patients.
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