Big advancements were announced across the board at the 2025 American Society of Clinical Oncology (ASCO) meeting. Phase 3 randomized clinical trials test how well a new therapy compares to the current standard of care, and results from these studies have the potential to change how breast cancer is treated. There were five presentations of new phase 3 clinical trial results for breast cancer at this year’s meeting, suggesting that changes in clinical practice may be just around the corner.
Advances in Metastatic Breast Cancer (MBC)
ER-positive breast cancer
ER-positive MBCs are typically treated with an aromatase inhibitor plus CDK4/6 inhibitor. Still, these cancers will inevitably progress on this treatment. Progression occurs when the tumor becomes resistant to treatment. In this case, ER-positive tumors will likely develop resistance to treatment due to an ESR1 mutation.
The SERENA-6 trial sought to determine if switching treatment when an ESR1 mutation appears, rather than wait for progression on an imaging scan, can extend the time before the cancer progresses, known as progression-free survival (PFS). In the trial, participants had their blood tested every 2-3 months for ESR1 mutations and were then randomized to switch to an oral selective estrogen receptor degrader (SERD) (a type of hormone therapy) called camizestrant or to remain on their aromatase inhibitor when a mutation appeared. Participants who switched to camizestrant had a median PFS of 16 months, compared to 9.2 months for those who remained on aromatase inhibitors. This is the first phase 3 trial showing potential for monitoring MBC using ctDNA to outsmart treatment resistance. Further insight into whether this strategy improves overall survival is needed before it can be adopted into clinical practice.
The VERITAC-2 trial also aimed to improve outcomes for patients whose cancer have ESR1 mutations. The results showed that a drug called vepdegestrant was well tolerated and improved PFS by 2.9 months compared to fulvestrant, a SERD that requires monthly injections. The results suggest that vepdegestrant, a medication that can be taken orally, may become a new option for patients with ESR1 mutated metastatic ER-positive breast cancer.
HER2-positive breast cancer
For more than 12 years, the standard of care for someone diagnosed with HER2-positive MBC has been chemotherapy combined with trastuzumab and pertuzumab. The DESTINY-Breast09 trial tested whether the antibody-drug conjugate trastuzumab deruxtecan (T-DXd) combined with pertuzumab is more effective than the current first line standard of care. Results showed that the T-DXd/pertuzumab combination improved progression-free survival by 13.8 months compared to the standard of care. Given this dramatic improvement, T-DXd will likely become a new option for initial treatment of metastatic HER2-positive breast cancer. However, T-DXd can come with significant side effects. Important issues that need to be addressed include determining who needs T-DXd the most up-front and the amount they need.
Triple negative breast cancer
Metastatic triple negative breast cancer (TNBC) is aggressive, and people desperately need better options to treat this disease up-front. Pembrolizumab plus chemotherapy is the current first-line standard of care for people diagnosed with metastatic PD-L1-positive TNBC. The ASCENT-04 trial showed that replacing chemotherapy with the antibody drug conjugate sacituzumab govitecan improved PFS by 3.4 months. With this improvement, sacituzumab govitecan plus pembrolizumab is poised to become the new first line standard of care for metastatic TNBC upon FDA approval.
Advances in Early Breast Cancer
ER-positive breast cancer
The menopausal-like side effects of hormone therapy can be severe enough that those taking it may reduce their dose or discontinue treatment early. There are few options available for treating these symptoms, and none are specifically approved for people with breast cancer. Results from the phase 3 OASIS-4 trial showed that a new drug called elinzanetant was able to significantly decrease the frequency of moderate to severe hot flashes caused by hormone therapy compared to a placebo. This may offer a new option to help improve the quality of life for people receiving hormone therapy for breast cancer.
HER2-positive breast cancer
The ongoing Komen-supported phase 2 CompassHER2 pCR study aims to determine if people with early HER2-positive breast cancer can safely forgo chemotherapy after surgery if their initial treatment with THP (chemotherapy, trastuzumab and pertuzumab) led to their cancer disappearing. While we are awaiting results on patient outcomes using this strategy, researchers reported that 64% of participants with HER2+/ER- breast cancer had their cancers disappear after their initial treatment. Researchers also showed that a new genomic test called HER2DX, could help predict the tumors most likely to disappear after initial treatment. These insights move us one step forward in right-sizing treatment of early HER2-positive breast cancer.
Staying On Top of Research Updates
This year’s ASCO meeting brought many promising advancements in breast cancer care across all stages and types of breast cancer. Komen will closely monitor changes to clinical practice guidelines and will update the relevant About Breast Cancer pages with the latest evidence-based information. You can also learn more about these highlights and more from ASCO through our upcoming MBC Impact Series and Breast Cancer Breakthroughs Series events.
