Four advances in breast cancer research presented at the 2025 European Society for Medical Oncology (ESMO) Congress could shape treatment approaches. Every fall, thousands of cancer experts from around the world gather at ESMO to share the latest research, and this year’s meeting delivered a wave of promising phase 3 clinical trial results.
Here are four key outcomes from ESMO 2025:
1. Trastuzumab deruxtecan may make its way into treating early HER2-positive breast cancer
For years, the go-to treatment for early-stage HER2-positive (HER2+) breast cancer has included chemotherapy plus trastuzumab and pertuzumab. But results from two phase 3 trials testing the antibody drug conjugate (ADC), trastuzumab deruxtecan (TDXd), in early HER2+ breast cancer in the adjuvant (after surgery) and neoadjuvant (before surgery) settings may signal a shift in this treatment paradigm.
The DESTINYBreast05 trial tested TDXd in people with high-risk residual disease who already had surgery. The results showed it cut the risk of cancer coming back by more than 50% compared to another ADC called T-DM1, suggesting this option may be more effective at reducing the risk of recurrence.
In the DESTINYBreast11 trial, T-DXd was used before surgery and led to a significantly higher rate of pathologic complete response (pCR) compared to chemotherapy, meaning that no cancer was found in tissue samples at the time of surgery. Longer follow-up will be needed to determine how this impacts outcomes.
2. First-line treatments may improve metastatic triple negative breast cancer (TNBC)
For those diagnosed with metastatic TNBC, treatment options have been limited, especially for those who are not eligible for immunotherapy, but that may be changing. Results from the ASCENT03 trial showed the ADC, sacituzumab govitecan, outperformed standard chemotherapy as a first-line treatment for immunotherapy-ineligible people with TNBC. It reduced the risk of disease progression by 38%, improving how long patients lived without their cancer worsening.
Likewise, the TROPIONBreast02 trial introduced another promising ADC for patients with metastatic TNBC. Datopotamab deruxtecan improved overall survival compared to chemotherapy, marking the first time an ADC has shown this benefit in first-line treatment of metastatic TNBC.
3. New data strengthens benefit of CDK4/6 inhibitors in early hormone receptor-positive (HR+) breast cancer
Two large studies reported long-term follow-up in early HR+/HER2- breast cancer, a group where preventing recurrence over many years is one goal. The CDK4/6 inhibitors abemaciclib and ribociclib have been used for some of these patients at a higher risk of recurrence, and these trials are reporting updates on patients who are 5 or more years out from starting these regimens.
After following participants for a median of 6.3 years, results from the monarchE trial showed that adding abemaciclib (a CDK4/6 inhibitor) to hormone therapy reduced the risk of death by 15.8% in those with high-risk early HR+/HER2- breast cancer. This is the first CDK4/6 inhibitor shown to improve overall survival in early breast cancer. The results also showed that fewer people in the abemaciclib group were living with metastatic cancer compared to those who received hormone therapy alone, suggesting that the treatment is reducing the risk of metastatic recurrence.
Additionally, the five-year update from the NATALEE trial showed that ribociclib plus aromatase inhibitors continued to show a reduced risk of recurrence compared to aromatase inhibitors alone in a broad group of people with early HR+ breast cancer.
These trials show promise for keeping breast cancer at bay in the long-term, but data will continue to be monitored for more clarity.
4. Positive results for selective estrogen receptor degraders (SERDs) in those with wild-type (unmutated) ESR1
Even the most effective hormone therapies can stop working for some people with metastatic HR+ breast cancer, often due to mutations in the ESR1 gene. SERDs are a type of therapy designed to shut down the receptor entirely, and currently, oral SERDs are only used in people whose breast cancers have ESR1 mutations. The evERA trial studied giredestrant, an oral SERD, combined with everolimus, an mTOR inhibitor, in people with HR+/HER2- metastatic breast cancer who had previously been treated with a CDK4/6 inhibitor. The results showed a 62% reduction in the risk of progression compared to standard hormone therapy in the entire study group, not just in cancers with ESR1 mutations. This is a promising sign that oral SERDs like giredestrant could become available to more people with estrogen receptor-positive metastatic breast cancer.
Progress continues for breast cancer treatment
Altogether, these updates from ESMO 2025 highlight how breast cancer care continues to move toward more effective treatments, reflect meaningful progress and gain momentum toward care that’s tailored to every individual’s diagnosis, risk and needs. Results from phase 3 clinical trials have the potential to change breast cancer care. Komen is closely monitoring changes to clinical practice guidelines and will update the relevant About Breast Cancer pages with the latest evidence-based information as it continues to develop.
If you or a loved one needs information or resources about clinical trials, please call our Breast Care Helpline at 1-877 GO KOMEN (1-877-465-6636) or email at clinicaltrialinfo@komen.org to connect with a trained specialist. Our caring and trained staff provide support and education about clinical trials to help people gain a better understanding of clinical trials.
