Experts Highlight HR+ and TNBC Trials to Watch Ahead of SABCS 2025

As anticipation builds for the 2025 San Antonio Breast Cancer Symposium (SABCS), OncLive® asked leading breast cancer specialists to share the hormone receptor (HR)–positive and triple-negative breast cancer (TNBC) presentations they are most eager to follow at this year’s meeting.

We gathered exclusive insights from:

• Jason Mouabbi, MD, an assistant professor in the Department of Breast Medical Oncology at The University of Texas MD Anderson Cancer Center in Houston
• Kelly McCann, MD, PhD, an assistant clinical professor of medicine at the UCLA Health David Geffen School of Medicine
• Elizabeth Sakach, MD, an assistant professor in the Department of Hematology and Medical Oncology at Emory University School of Medicine in Atlanta, Georgia

Several high-impact studies and educational sessions in HR-positive breast cancer and TNBC will be in focus at this year’s SABCS, with the potential to influence both early-stage and metastatic treatment paradigms. Key presentations include the phase 3 lidERA trial (NCT04961996), which may position the oral SERD giredestrant as the first agent in its class to improve invasive disease-free survival (iDFS) in the adjuvant setting.1 Updated clinical and biomarker analyses from phase 3 evERA Breast Cancer (NCT05306340) evaluating giredestrant plus everolimus (Afinitor) following progression on CDK4/6 inhibition will be presented following initial data at the 2025 ESMO Congress.2 Complementing these scientific presentations, Educational Session 4 will examine the role of hormone replacement therapy in breast cancer care—an increasingly important topic given evolving evidence and persistent quality-of-life concerns for patients receiving long-term endocrine therapy.

In the TNBC setting, attention will turn to phase 3 ASCENT-07 (NCT05840211), a phase 3 trial evaluating sacituzumab govitecan-hziy (Trodelvy) vs physician’s choice chemotherapy in endocrine-refractory HR-positive/HER2-negative disease.3

GS1-10- 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

Mouabbi: I am very much looking forward to the presentation of the lidERA trial, especially following the recent press release announcing that the study met its primary end point. This is a potentially practice-changing moment, as giredestrant is the first oral SERD to demonstrate a statistically significant improvement in iDFS in the adjuvant setting. Given the challenges we face with adherence and resistance to standard endocrine therapy in early-stage estrogen receptor–positive/HER2-negative breast cancer, having a novel, oral option that outperforms the standard of care is a major milestone. I am eager to see the magnitude of the iDFS benefit and the safety data, which will determine if this agent is poised to become the new backbone for adjuvant treatment.

GS3-09: Clinical and biomarker subgroup analysis of evERA Breast Cancer: A Phase III trial of giredestrant plus everolimus in patients with estrogen receptor-positive, HER2-negative advanced breast cancer previously treated with a CDK4/6 inhibitor

Sakach: Given the exciting positive results presented at ESMO [2025] with giredestrant improving PFS in metastatic disease and iDFS in early breast cancer, it will be interesting to understand the clinical biomarker results and whether there is a specific population benefiting from this oral SERD, or [whether] should we consider the use of giredestrant in all patients after progression on CDK4/6i in the metastatic setting.

Educational Session 4: Balancing Act—Hormone Replacement Therapy in Breast Cancer Care

Sakach: I am very interested to tune into the educational session regarding hormone replacement therapy in breast cancer care. Given the changing landscape with data regarding hormone replacement therapy, this session will be important to address the myths and tailored considerations for high-risk individuals, ideally bringing strategies to patients who struggle for years on adjuvant endocrine therapy with significant symptoms and adverse effect to their quality of life.

GS1-09 Sacituzumab govitecan vs chemotherapy as first therapy after endocrine therapy in HR+/HER2− (IHC 0, 1+, 2+/ISH−) metastatic breast cancer: Primary results from ASCENT-07

McCann: Sacituzumab govitecan was recently shown at ESMO 2025 and ASCO 2025 to confer a PFS benefit over chemotherapy of physician's choice in the first-line metastatic TNBC setting in [the phase 3] ASCENT-03 trial [NCT05382299] and in combination with pembrolizumab [Keytruda] in [the phase 3] ASCENT-04 study [NCT05382286]. [Sacituzumab govitecan] is FDA-approved for metastatic HR-postive/HER2-negative breast cancer as a second-line or greater treatment for endocrine-refractory disease, based on [data from the phase 3] TROPiCS-02 trial [NCT03901339].

ASCENT-07 is a phase 3 study evaluating sacituzumab govitecan vs chemotherapy of physician's choice in patients with HR-positive/HER2-negative metastatic breast cancer with endocrine therapy–refractory disease. [The phase 3] DESTINY-Breast06 trial [NCT04494425] with fam-trastuzumab deruxtecan-nxki [Enhertu] was a similar design but excluded patients with HER2 immunohistochemistry [IHC] 0 [disease] but inclusion of patients with ultralow HER2 expression, which is defined as HER2 IHC staining in less than 10% of the sample. In DESTINY-Breast06, approximately 60% of the patients on the standard-of-care arm received capecitabine. Sacituzumab govitecan was not significantly significant in terms of median PFS to the chemotherapy to which it was compared [in ASCENT-07].

A careful re-evaluation of the patient population enrolled is warranted, as well as consideration of the fundamental tumor biology differences between metastatic TNBC in the first-line metastatic setting, which typically has a very aggressive biology with high TROP2 expression, and HR-positive/HER2-negative breast cancer in the second- or third-line metastatic setting, which is usually slower-growing than TNBC, often not as widespread, and is less likely to have high TROP2 expression. If other TROP2 ADCs such as datopotamab deruxtecan [Datroway] suffer a similar fate in the same setting, I hypothesize that TROP2 expression levels are indeed important and may increase as HR-positive/HER2-negative tumors evolve into a more aggressive biology.

References

1. [Ad hoc announcement pursuant to Art. 53 LR] Roche’s giredestrant becomes the first oral SERD to show superior invasive disease-free survival in early breast cancer. Roche. News Release. November 17, 2025. Accessed December 5, 2025. https://www.roche.com/media/releases/med-cor-2025-11-18
2. Mayer E, Tolaney SM, Martin M, et al. Giredestrant (GIRE), an oral selective oestrogen receptor (ER) antagonist and degrader, + everolimus (E) in patients (pts) with ER-positive, HER2-negative advanced breast cancer (ER+, HER2– aBC) previously treated with a CDK4/6 inhibitor (i): Primary results of the phase III evERA BC trial. Presented at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Abstract LBA16.
3. Gilead provides update on phase 3 ASCENT-07 study. News release. Gilead. November 7, 2025. Accessed December 5, 2025. https://www.gilead.com/news/news-details/2025/gilead-provides-update-on-phase-3-ascent-07-study