Experts Highlight SABCS 2025 Data With Potential to Shift Breast Cancer Practice

The 2025 San Antonio Breast Cancer Symposium (SABCS) delivered clinically meaningful data across breast cancer subtypes, highlighting advances in HER2-targeted maintenance strategies and next-generation endocrine therapy in early-stage disease.

Key phase 3 presentations from SABCS included findings from the HER2CLIMB-05 trial (NCT05132582), which evaluated tucatinib (Tukysa) vs placebo in combination with trastuzumab (Herceptin) and pertuzumab (Perjeta) as maintenance therapy for patients with HER2-positive metastatic breast cancer, as well as results from the lidERA Breast Cancer trial (NCT04961996), which compared the oral selective estrogen receptor degrader (SERD) giredestrant (GDC-9545) vs standard-of-care (SOC) adjuvant endocrine therapy in patients with estrogen receptor–positive, HER2-negative early breast cancer.1,2

OncLive® spoke with leading breast cancer specialists throughout the meeting to capture their perspectives on the most influential presentations and how these findings may translate into near-term clinical practice. Read on for insights from:

• Daniella Audi Blotta, MD, a medical oncologist and research fellow in Breast Cancer at Memorial Sloan Kettering Cancer Center in New York
• Aditya Bardia, MD, MPH, FASCO, director of Translational Research Integration and a professor in the Department of Medicinein the Division of Hematology/Oncology at the UCLA Health Jonsson Comprehensive Cancer Center in Los Angeles, California
• Massimo Cristofanilli, MD, associate director of Precision Oncology at the Meyer Cancer Center (MCC), co-leader of the MCC Breast Cancer Disease Management Team, and scientific director of the Englander Institute of Precision Medicine at Weill Cornell Medicine in New York, New York
• Erika P. Hamilton, MD, FASCO, chair of the Breast Executive Committee and director of the Breast Cancer Research Program at Sarah Cannon Research Institute, as well as a medical oncologist at Tennessee Oncology in Nashville
• Erica Mayer, MD, MPH, director of Breast Cancer Clinical Research and a medical oncologist at Dana-Farber Cancer Institute, as well as an associate professor of medicine at Harvard Medical School in Boston, Massachusetts

Her2climb-05: a randomized, double-blind, phase 3 study of tucatinib versus placebo in combination with trastuzumab and pertuzumab as maintenance therapy for her2+ metastatic breast cancer

Bardia: I was excited to see the results of HER2CLIMB-05, which showed that the addition of tucatinib plus trastuzumab/pertuzumab is associated with improvement in progression-free survival (PFS). If approved, [this combination] could [be] another treatment option for patients with metastatic HER2-positive breast cancer.

ASCENT-07 study investigating sacituzumab govitecan-hziy vs chemotherapy as a first-line treatment post-endocrine therapy in HR+/HER2-negative metastatic breast cancer

Audi Blotta: The ASCENT-07 trial evaluated sacituzumab govitecan (Trodelvy) in the first-line setting after endocrine therapy for patients with hormone receptor–positive, HER2-negative metastatic breast cancer. The results were negative in terms of PFS, but this [trial answered] an important clinical question, even with negative results.

Giredestrant vs standard-of-care endocrine therapy as adjuvant treatment for patients with estrogen receptor-positive, HER2-negative early breast cancer: Results from the global Phase III lidERA Breast Cancer trial

Mayer: The abstract I’m thinking about the most is [lidERA], as this is the first endocrine treatment that we’ve had in 25 years to demonstrate benefit in the early-stage setting. This is a groundbreaking finding, but I would add that the report from [lidERA] is the first from a host of incredibly large adjuvant oral SERD studies.

Some of these trials are enrolling patients immediately at the time when they initiate adjuvant endocrine therapy. Some of them are enrolling patients over more of an extended duration, 2 to 5 years out from starting endocrine therapy. There are trials that also incorporate CDK4/6 inhibitors.

Over the next few years, as we see readouts from these trials, this is going to influence how we make decisions for patients in the adjuvant setting. It may also begin to tell us that we’re going to sweep away aromatase inhibitors and enter into a setting where oral SERDs are our preferred option for patients—a selection that may improve efficacy, tolerability, and adherence, and hopefully allow us to cure more patients with breast cancer. We’re seeing the prelude to what’s going to be an extraordinary next few years in breast cancer.

Hamilton: One of the datasets that is potentially practice changing is the [lidERA] data around adjuvant [giredestrant]. This was exciting, mainly because we haven’t had a change in endocrine backbones in excess of 20 years. I see a lot of people saying we haven’t had changes to adjuvant endocrine therapy, and I don’t completely agree with that. We have had the addition of CDK4/6 inhibitors—both [abemaciclib (Verzenio)] and [ribociclib (Kisqali)].

However, to see an approximate 3% benefit already at this first initial look at 36 months of follow-up in an all-comer population not selected for [ESR1 mutations] is validating for the oral SERDs. We have some difficult decisions ahead of us, because it’s hard to consider giving up the benefit of an adjuvant CDK4/6 inhibitor. There are going to have to be some conversations with patients. But ultimately, CDK4/6 inhibitors have a bit more magnitude of benefit and a bit longer follow-up.

Cristofanilli: I agree that lidERA is probably the most impactful news of the [meeting], because we didn’t have an agent approved that setting—except for a CDK4/6 inhibitor in the adjuvant setting—for a long time. We are all excited about how the field is changing. The SOC is changing. The comparison is changing. Where we place [giredestrant] in the context of the treatment we have right now with CDK4/6 inhibitors will be a great debate in the months and hopefully even in the years to come. Having new opportunities for treatment is important for patients with breast cancer.

References

1. Hamilton E, Curigliano G, Martin M, et al. HER2CLIMB-05: a randomized, double-blind, phase 3 study of tucatinib versus placebo in combination with trastuzumab and pertuzumab as maintenance therapy for HER2+ metastatic breast cancer. Presented at: 2025 San Antonio Breast Cancer Symposium; December 9-12, 2025; San Antonio, TX. Abstract GS1-01.
2. Bardia A, Schmid P, Martín M, et al. Giredestrant vs standard-of-care endocrine therapy as adjuvant treatment for patients with estrogen receptor-positive, HER2-negative early breast cancer: results from the global phase III lidERA Breast Cancer trial. Presented at: 2025 San Antonio Breast Cancer Symposium; December 9-12, 2025; San Antonio, TX. Abstract GS1-10.