Key HR+, Early Breast Cancer Abstracts From SABCS 2025
Key Points
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The ALTTO trial suggested aromatase inhibitors (AIs) are more effective than tamoxifen in hormone receptor (HR)–positive early-stage breast cancer
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Giredestrant, an oral selective estrogen receptor degrader (SERD), outperformed standard adjuvant endocrine therapy in the lidERA trial.
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Data from the NATALEE study continue to show that adding ribociclib to conventional adjuvant therapy improves disease-free survival (DFS).
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Additional trials are needed to inform optimal sequencing and combination strategies for novel therapies in the early-stage setting.
ALTTO, lidERA, and NATALEE Data at SABCS 2025
Cohosts of the Oncology Brothers podcast, Rahul Gosain, MD, MBA, of Wilmot Cancer Institute, and Rohit Gosain, MD, of Roswell Park Comprehensive Cancer Center, invited Laura Huppert, MD, of UCSF School of Medicine, to discuss three of the most impactful studies in HR–positive, early-stage breast cancer presented at the 2025 San Antonio Breast Cancer Symposium (SABCS 2025).
Adjuvant AIs Versus SERMs in ALTTO Trial
The phase 3 ALTTO trial evaluated four adjuvant therapies in patients with HR-positive, HER2–positive, early breast cancer. An exploratory analysis compared DFS, time to distant recurrence (TTDR), and overall survival (OS) between patients treated with an AI and those treated with a selective estrogen receptor modulator (SERM; tamoxifen for 99.5% of participants).
At 10 years, the AI and SERM arms had DFS rates of 80.1% and 76.5% (adjusted hazard ratio [aHR], 0.65; 95% CI, 0.52-0.82), TTDR rates of 85.7% and 83.1% (aHR, 0.65; 95% CI, 0.50-0.85), and OS rates of 88.9% and 89.1% (aHR, 0.73; 95% CI, 0.53-1.00), respectively. The study found that AI was superior to SERM across patient, tumor, and treatment subgroups.
This is the most extensive analysis of adjuvant therapy in HER2–positive early-stage breast cancer, and the data emphasize that AIs are more effective than SERMs, particularly for high-risk patients, said Dr. Huppert.
lidERA Data Raise Giredestrant as Novel Endocrine Therapy Option
In the phase 3 lidERA trial, giredestrant, an oral SERD, was compared with standard endocrine therapy in patients with high-risk, estrogen receptor–positive, HER2–negative, early-stage breast cancer. Giredestrant improved invasive DFS (HR, 0.70; 955 CI, 0.57-0.87; P = .0014) and distant recurrence-free interval (HR, 0.69; 95% CI, 0.54-0.89), and showed a trend toward improved OS (HR, 0.79; 95% CI, 0.56-1.12), according to the SABCS 2025 presentation.
This was one of the most discussed studies from SABCS 2025, as the first positive study for an oral SERD in the adjuvant setting. Standard-of-care endocrine therapy has consisted of AIs and SERMs for over 20 years, and the potential to incorporate oral SERDs is practice-changing, said Dr. Huppert.
Notably, patients in lidERA could not receive giredestrant concurrently with CDK4/6 inhibitors, which have become standard of care in adjuvant therapy for early-stage breast cancer based on the monarchE and NATALEE trials. Although combinations of SERDs and CDK4/6 inhibitors have shown reassuring safety in the metastatic setting, additional trials are needed in early-stage disease. In the short term, Dr. Huppert said she may complete a 2- or 3-year course of adjuvant abemaciclib or ribociclib plus AI per the MONARCHE or NATALEE protocols, then switch the AI to giredestrant.
NATALEE Update Shows Adjuvant CDK4/6 Inhibitor Benefit
The NATALEE trial previously showed adjuvant ribociclib with non-steroidal aromatase inhibitor (NSAI) improved invasive DFS and distant DFS versus NSAI alone in patients with high-risk, HR–HR-positive, HER2–negative early breast cancer. The SABCS 2025 presentation covered updated distant DFS outcomes across clinically relevant subgroups. Overall, adjuvant ribociclib continued to show a distant DFS (HR, 0.709; 95% CI, 0.608-0.827; P < .0001) benefit versus NSAI, regardless of disease stage, nodal status, menopausal status, age, prior endocrine therapy duration, and Ki-67 status.
“Based on these additional data and the 5-year follow-up, I feel very comfortable using ribociclib in all patients that meet criteria and are motivated… even in those node-negative patients, even in those stage II patients,” said Dr. Huppert.