The San Antonio Breast Cancer Symposium 2025 showcased major clinical trial updates shaping the future of breast cancer treatment, from early-stage endocrine strategies to evolving therapies in metastatic HER2-positive and triple-negative disease, as reviewed by a practicing oncologist.

The San Antonio Breast Cancer Symposium (SABCS) 2025 featured several exciting presentations.

Early Breast Cancer: Clinical Trial Highlights

In the early breast cancer (EBC) setting, three trials stood out for me:

1. The LORETTA trial

This trial focused on low-risk, low-grade, strongly estrogen-positive DCIS. This prospective single-arm study randomized 340 patients to receive tamoxifen (20 mg for 5 years), aiming for a cumulative incidence of ipsilateral invasive breast cancer under 7%. Unfortunately, the primary endpoint was not achieved, with a cumulative incidence of 9.8%. This result suggests that there remains a role for surgery and radiation in this patient group in removing an evolving index lesion. Furthermore, a lower dose of Tamoxifen, at 5 mg or 10 mg every other day for 3 years, demonstrated overall good tolerance.

2. The Italian TAM01 trial

This was previously presented at SABCS 2022. It showed a 42% reduction in breast cancer recurrence (both invasive and DCIS) over a 10-year follow-up, with a significant carry-over effect lasting up to 7 years after the treatment ceased. TAM 01 also showed a 74% reduction in the risk of contralateral breast cancer. This evidence points to the need for multi-disciplinary care in managing DCIS, particularly given that non-compliance rates to endocrine therapy (ET) can be as high as 50%. The ongoing “Lo Tam” trial (NCT06671912) is evaluating this lower-dose Tamoxifen strategy by randomizing postmenopausal patients with low-grade lymph node negative disease to either standard aromatase inhibitors or 20 mg Tamoxifen for 5 years versus the lower 10 mg every other day. Enrollment will likely be completed in 2026.

Another significant focus for me was on carboplatin in the neoadjuvant treatment of triple-negative breast cancer. A pooled analysis of the BrightNess, CALGB 40603, and GeparSixto studies found that adding carboplatin to the neoadjuvant regimen significantly improved pathologic complete response rates (55% compared to 38.9%) and 5-year event-free survival (EFS) rates (77% vs. 69%). Notably, these benefits were observed not only in BRCA mutation carriers but also in wild-type BRCA patients. There is still an important role for carboplatin in early triple-negative breast cancer treatment, along with the addition of immunotherapy per Keynote 522.

Other triple-negative EBC considerations include the role of anthracyclines. The SCARLET trial (Shorter Anthracycline free chemo immunotherapy adapted to pathological response) is randomizing patients to the standard of care Keynote 522 regimen versus the no anthracycline shorter six-cycle “TC” (taxane carboplatin) regimen. In HER2+ EBC, the carboplatin role has been challenged with THP as non-inferior to TCHP in pathologic complete response rates in the deescalation neoCARHP study (ASCO 2025), and we await event-free survival from Compass HER2.

3. The LidERA trial

A EBC SABCS highlight was the landmark LidERA trial, which explored the efficacy of the oral selective estrogen receptor degrader (SERD), giredestrant, in the adjuvant treatment of moderate to high-risk early breast cancer, regardless of ESR1 mutation status. This randomized trial compared the oral SERD, giredestrant, with standard endocrine therapy over at least five years. The primary endpoint of invasive disease-free survival (IDFS) showed a hazard ratio of 0.70, indicating a 30% improvement. This data is exciting as giredestrant is the first new endocrine agent introduced in over 20 years.

While the main side effects were arthralgias and hot flashes, it is worth noting that approximately 40% of participants were premenopausal and required ovarian function suppression. The standard care arm had a higher treatment discontinuation rate of 4.4% compared to 1.8% for Giredestrant, largely due to arthralgias. Additionally, 11.3% of patients experienced grade 1-2 bradycardia with giredestrant, though there were no severe cases. Importantly, none of the patients in this trial received combinations with CDK4/6 inhibitors, which is an important adjuvant standard of care in high-risk EBC.

Further data from the MonarchE trial presented at ESMO 2025 showed a sustained overall survival benefit of 1.8% and a significant reduction in mortality risk with the combination of abemaciclib and endocrine therapy. There is ongoing interest in the adjuvant data from the LidERA substudy, which has enrolled patients receiving abemaciclib. Several oral SERD adjuvant trials are ongoing, such as the EMBER 4 study, which has complete enrollment (n=8000) and randomized high-risk EBC patients to imlunestrant or continued ET therapy after 2-5 years of ET, potentially including CDK 4/6 inhibitor therapy.

Metastatic Breast Cancer: Clinical Trial Highlights

In the metastatic breast cancer (MBC) arena, the EMBER 3 study, presented by Dr. Jhaveri, provided updated efficacy results, including a numerical trend in overall survival at 50% maturity in hormone receptor-positive (HR+) MBC space after progression on a prior CDK 4/6 inhibitor (mostly palbociclib). The imlunestrant monotherapy arm reported a median overall survival of 34.5 months against 23.1 months for the standard endocrine therapy arm among patients with ESR1 mutations; however, it should be noted that this finding is not yet statistically significant. Imlunestrant received FDA approval on 9/25/2025 for ESR1 mutation MBC based on a median progression-free survival (PFS) endpoint, and subgroup analyses revealed important and consistent outcomes (similar to the EMERALD trial with Elacestrant) for patients who had previously received CDK4/6 inhibitors.

At ESMO, the eVERA trial highlighted results from combining giredestrant with everolimus, which showed a 62% improvement in PFS for ESR1 mutation patients. Dr. Rugo presented subgroup analysis of eVERA at SABCS, including the prior CDK 4/6 inhibitor patients as well, helping further refine “endocrine or hormone sensitive” disease in the HR+ MBC space.

First-Line Treatment Evolution in HER2-Positive Metastatic Breast Cancer

The field of HER2-positive metastatic breast cancer, including first-line therapy, continues to evolve, as evidenced by the HER2 Climb 5 trial, which investigated the addition of tucatinib to maintenance therapy HP (trastuzumab/pertuzumab) after induction with the first-line Cleopatra taxane chemotherapy (T) HP. The HER2 Climb 5 trial demonstrated improved investigator-assessed PFS from 16.3 months to 24.9 months with tucatinib (HR=0.64). In the context of the first-line Cleopatra arm, the THP median PFS was 18.5 months, while the Destiny Breast 09 study control THP arm reported at 26.9 months.

The PATINA trial (SABCS 2024) had a control arm PFS of 29.1 months, where patients continued endocrine therapy along with HP maintenance without palbociclib. The placebo +HP control arm PFS in HER2 Climb 5 is curious. Notably, approximately 52% of participants in the HER2 Climb 5 trial had triple-positive metastatic breast cancer, and around 70% presented with de novo HER2-positive metastatic disease. The PFS benefit from Tucatinib appeared more pronounced among HR-negative HER2-positive patients, with a 12.3-month PFS improvement. Moreover, patients with baseline brain metastasis also benefited from Tucatinib, and overall survival is not yet mature.

This raises important clinical considerations regarding the potential addition of tucatinib in the HR-negative population as compared to using palbociclib in HR-positive HER2+ first-line maintenance settings.

Disclaimer: Impressions of SABCS 2025 highlights are solely the opinion of Dr. Milana Dolezal

About Author

Dr. Dolezal is a board-certified hematologist-oncologist with Stanford Medicine Cancer Center in Emeryville and a clinical associate professor in the Stanford School of Medicine, Division of Oncology. She has extensive experience in research and drug development. She previously held positions as a clinical scientist, assistant medical director, and associate medical director in the BioOncology Therapeutics unit of the biotechnology company Genentech. She has conducted clinical research into fertility preservation in patients with breast cancer, advanced treatments for triple-negative breast cancer, and patients’ adherence to anti-cancer therapy. She has co-authored articles on her research findings that appeared in the Journal of Clinical Oncology, Cancer, and other peer-reviewed publications. Dr. Dolezal has made presentations to her peers at meetings of the American Association for Cancer Research, American Society of Clinical Oncology, and European Cancer Organisation.