SABCS 2025: The Top 5 Takeaways for Breast Cancer Research

At the 2025 San Antonio Breast Cancer Symposium (SABCS), expert clinicians and researchers convened to share promising developments in breast cancer intervention. Across several oral presentations, investigators revealed key data and outcomes associated with novel immunotherapeutic regimens, radiation- and surgery-based modalities, and investigational technology for protecting patient quality of life (QOL).

CancerNetwork® reported on the newest advancements and data readouts to come from these sessions. Here are the top 5 takeaways from SABCS 2025 that have the potential to influence the future of breast cancer care.

#1: Frontline Giredestrant Displays IDFS Improvement vs SOC ET in ER+/HER2– BC

In the phase 3 lidERA Breast Cancer trial (NCT04961996), giredestrant (GDC-9545), a next-generation selective estrogen receptor degrader (SERD), improved invasive disease-free survival (IDFS) compared with standard-of-care (SOC) endocrine therapy among those with estrogen receptor (ER)–positive, HER2-negative early breast cancer.¹

The experimental agent reduced the risk of invasive disease recurrence or death vs SOC therapy by 30% (HR, 0.70; 95% CI, 0.57-0.87; P = .0014). Additionally, the IDFS rates in the giredestrant and comparator arms, respectively, were 97.7% vs 96.9% at 12 months, 94.6% vs 92.3% at 24 months, and 92.4% vs 89.6% at 36 months.

“With a median follow-up of 32.6 months, lidERA demonstrated a clinically meaningful and statistically significant improvement with [frontline] giredestrant over [SOC] endocrine therapy in ER-positive, HER2-negative early breast cancer,” presenting investigator Aditya L. Bardia, MD, MPH, FASCO, a professor in the Department of Medicine of the Division of Hematology/Oncology and director of Translational Research Integration at the University of California, Los Angeles Health, stated in a press briefing regarding these outcomes.

#2: Sacituzumab Govitecan Does Not Meet Statistical Significance in HR+/HER2– mBC

Progression-free survival (PFS) did not appear to significantly improve with sacituzumab govitecan-hziy (Trodelvy) following endocrine therapy vs chemotherapy among patients with hormone receptor (HR)–positive, HER2-negative breast cancer, according to data from the phase 3 ASCENT-07 study (NCT05840211).²

Data showed a median PFS of 8.3 months (95% CI, 8.1-10.3) in the sacituzumab govitecan arm as well as 8.3 months (95% CI, 6.9-10.0) in the chemotherapy arm based on blinded independent central review (BICR; HR, 0.85; 95% CI, 0.69-1.05; P = .130). Per investigator evaluation, the median PFS was 8.4 months (95% CI, 8.2-9.7) and 6.4 months (95% CI, 6.0-8.1) in each respective arm (HR, 0.78; 95% CI, 0.64-0.93; P = .008).

According to presenting investigator Komal Jhaveri, MD, FACP, FASCO, section head of the Endocrine Therapy Research Program, clinical director of Early Drug Development Services, and the Patricia and James Cayns Chair for Junior Faculty at Memorial Sloan Kettering Cancer Center, sacituzumab govitecan nevertheless “remains a standard of care for HR-positive/HER2-negative metastatic breast cancer after prior endocrine therapy and chemotherapy based on the phase 3 TROPiCS-02 study [NCT03901339].”

#3: ALTERNATE Reveals Surgical Patterns After Neoadjuvant Breast Cancer Care

Long-term findings from the phase 3 ALTERNATE trial (NCT01953588) revealed key patterns in the use of surgery and neoadjuvant therapy across a large cohort of patients with stage II/III ER-positive, HER2-negative breast cancer.³

For example, presenting study investigator A. Marilyn Leitch, MD, stated that knowing if a patient had node positivity from “needle biopsy pretreatment influenced the management of the nodal basin at the time of definitive surgery,” as axillary dissection was less frequently employed “for a positive sentinel node if the patient was clinically node negative prior to neoadjuvant therapy,” especially for patients who had breast-conserving surgery (BCS). Additionally, the omission of axillary dissection was more common for patients with “only 1 positive sentinel node compared with 2 or more,” although “patients with even more nodes did have omission of axillary dissection.”

“Long-term follow-up is required to assess local-regional recurrence for those who only had [sentinel lymph node biopsy] after having node-positive disease at diagnosis,” Leitch, from the Harold C. Simmons Comprehensive Cancer Center in Dallas, Texas, stated in her presentation.

#4: Pembrolizumab/Radiation Improves T Cell Infiltration in Early Breast Cancer

T-cell infiltration significantly improved with the use of pembrolizumab (Keytruda) plus radiotherapy among patients with node-positive, higher-risk, HR-positive, HER2-negative, early-stage breast cancer who were enrolled on the phase 2 TBCRC-053 (P-RAD) trial (NCT04443348).⁴

Patients who received radiation at 24 Gy plus pembrolizumab were noted to experience a statistically significant increase in T-cell infiltration for the primary tumor (P = .023); those with higher T-cell infiltration also tended to have higher levels of PD-L1 expression compared with those who did not experience high infiltration. Spatial transcriptomic analyses revealed an increased abundance of tertiary lymphoid structures after treatment with pembrolizumab plus radiation, which have correlated with enhanced responses to immunotherapy in other cancer types.

“Future trials examining preoperative radiation with pembrolizumab in HR-positive, HER2-negative breast cancer are needed and encouraged to clarify the disease control benefit that this may bring,” lead study investigator Gaorav Gupta MD, PhD, an assistant professor in the Department of Radiation Oncology at Lineberger Comprehensive Cancer Center of the University of North Carolina at Chapel Hill, noted in a presentation of the data.

#5: QOL Improvement in Breast Cancer Noted With YES System

Among adolescents and young adults with breast cancer, the Young, Empowered, and Strong (YES) mobile health intervention improved QOL while reducing burdensome symptoms in the YES clinical trial.⁵

Data showed a Quality of Life in Adult Cancer Survivors (QLACS) general summary score of 77.6 among 179 patients who used YES vs 78.1 in 181 patients who underwent usual care; higher QLACS scores correlated with worse QOL. Additionally, mean QLACS scores for general QOL decreased by 8.7 points in the YES arm vs 1.6 points in the usual care arm by 6 months.

“[YES] represents a novel paradigm for supporting patients without clinician involvement, for the most part, in the survivorship period and thus represents a potentially scalable public health effort for harder-to-reach populations who are busy, can't get into the clinic, and/or can't very easily access the clinic,” presenting study investigator Ann H. Partridge, MD, MPH, founder and director of the Program for Young Adults with Breast Cancer at Dana-Farber Cancer Institute, stated in a press briefing on these results.

References

1. 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.
2. Jhaveri K, Park YH, Barrios C, et al. 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. Presented at: 2025 San Antonio Breast Cancer Symposium; December 9-12, 2025; San Antonio, TX. Abstract GS1-09.
3. Leitch AM, Dockter T, Suman VJ, et al. Surgical outcomes in the ALTERNATE trial (Alliance A011106) -a randomized phase 3 neoadjuvant endocrine therapy (NET) trial in postmenopausal women with clinical stage II/III estrogen receptor positive (ER+) and HER2 negative (HER2-) breast cancer (BC). Presented at: 2025 San Antonio Breast Cancer Symposium; December 9-12, 2025; San Antonio, TX. Abstract RF1-02.
4. Gupta GP, Ho AY, Gharibpoor F, et al. Primary results from the HR+/HER2- cohort of TBCRC-053 (P-RAD): a randomized trial of no, low, or high dose preoperative RADiation with pembrolizumab and chemotherapy in node-positive, HER2-negative breast cancer. Presented at: 2025 San Antonio Breast Cancer Symposium; December 9-12, 2025; San Antonio, TX. Abstract GS2-05.
5. Partridge AH, Graham N, Dibble KE, et al. Randomized controlled trial of Young, Empowered & Strong (YES), an mHealth intervention for adolescent and young adult breast cancer survivors. Presented at: 2025 San Antonio Breast Cancer Symposium; December 9-12, 2025; San Antonio, TX. Abstract GS3-03.