Top 5 Breast Cancer Updates From the 2025 San Antonio Breast Cancer Symposium

At the 2025 San Antonio Breast Cancer Symposium (SABCS), researchers presented findings with the potential to meaningfully affect breast cancer treatment and patient care. From progress in hormone receptor (HR)–positive disease to advances in immunotherapy strategies, the following five updates stood out for their potential clinical and quality-of-life impact.

1. Giredestrant Improves Outcomes in ER+/HER2– Early Breast Cancer

Findings from the phase 3 lidERA study show that giredestrant (GDC-9545) improved invasive disease-free survival compared with standard endocrine therapy in patients with estrogen receptor (ER)–positive, HER2-negative medium- and high-risk early breast cancer.

After a median follow-up of 32.36 months, giredestrant reduced the risk of invasive disease recurrence or death by 30% versus standard endocrine therapy. The 12-, 24-, and 36-month invasive disease-free survival rates with giredestrant were approximately 97.7%, 94.6%, and 92.4%, compared with 96.9%, 92.3%, and 89.6% in the standard-of-care arm. These results position giredestrant as a potential next-generation endocrine therapy option for patients with higher-risk early disease.

2. Tukysa Combination Extends Frontline Maintenance in Advanced HER2+ Breast Cancer

The phase 3 HER2CLIMB-05 trial evaluated Tukysa (tucatinib) combined with Herceptin (trastuzumab) and Perjeta (pertuzumab) as maintenance therapy for patients with HER2-positive metastatic breast cancer whose disease had not progressed after docetaxel plus Herceptin and Perjeta.

With approximately 23 months of follow-up, median progression-free survival reached 24.9 months with the tucatinib regimen versus 16.3 months with placebo plus Herceptin and Perjeta. Benefit extended across every prespecified subgroup, including age, race, hormone receptor status, baseline brain metastases, disease site, and performance status. These findings highlight tucatinib as a potential new standard maintenance strategy for advanced HER2-positive disease.

3. Verzenio Shows Clinical Benefit After Prior CDK4/6 Therapy in HR+/HER2– Breast Cancer

Findings from the rAMBER study indicate that Verzenio (abemaciclib) monotherapy may provide meaningful activity for patients with HR-positive, HER2-negative metastatic breast cancer who had progressed on a previous CDK4/6 inhibitor.

Across four academic centers, approximately 33% of patients experienced clinical benefit on Verzenio, remaining on treatment for more than 180 days. Most patients continued therapy until disease progression or death, and tolerability remained acceptable even among individuals who previously received Ibrance (palbociclib) therapy and ongoing endocrine approaches. These results suggest that sequential CDK4/6-targeted strategies may offer continued disease control for select patients.

4. Radiation Plus Keytruda Before Surgery Enhances Immune Response in Early Breast Cancer

The phase 2 TBCRC-053 (P-RAD) trial evaluated Keytruda (pembrolizumab) delivered with preoperative radiation therapy in patients with node-positive, higher-risk, HR-positive and HER2-negative early-stage breast cancer.

Patients receiving 24 Gy radiation plus Keytruda demonstrated a statistically significant increase in T-cell infiltration within primary tumors. Tumors with heightened infiltration also showed increased PD-L1 expression. Gene expression analysis revealed broader immune activation, including increased B cells, natural killer cells, dendritic cells, and immunostimulatory macrophages.

These findings suggest that integrating immunotherapy with targeted radiation may enhance antitumor immune activity before surgery.

5. Radiation Plus Keytruda Produces Broad Immune Cell Activation Signals

A deeper analysis of the P-RAD dataset reinforced that the radiation and Keytruda combination increased T-cell penetration. Investigators also observed evidence of multiple immune cell populations entering tumors, potentially supporting a stronger and more durable response to therapy.

According to lead study presenter Dr. Gaorav Gupta, immune profiling demonstrated cellular diversity consistent with an activated tumor microenvironment. These findings support ongoing research into immunotherapy-radiation sequencing in early breast cancer and encourage exploration of response predictors for future patient selection.

References

1. “Giredestrant Improves Outcomes in ER+/HER2– Breast Cancer,” by Roman Fabbricatore. CURE; Dec. 10, 2025. https://www.curetoday.com/view/giredestrant-improves-outcomes-in-er-her2-breast-cancer
2. “Tukysa Combo Boosts Frontline Maintenance in Advanced HER2+ Breast Cancer,” by Caroline Seymour. CURE; Dec. 11, 2025. https://www.curetoday.com/view/tukysa-combo-boosts-frontline-maintenance-in-advanced-her2-breast-cancer
3. “Verzenio Offers Potential Benefit After Prior Therapy in HR+/HER2– Breast Cancer,” by Kyle Doherty. CURE; Dec. 11, 2025. https://www.curetoday.com/view/verzenio-offers-potential-benefit-after-prior-therapy-in-hr-her2-breast-cancer
4. “Radiation Plus Keytruda Before Surgery Boosts Immune Response in Breast Cancer,” by Russ Conroy. CURE; Dec. 11, 2025. https://www.curetoday.com/view/radiation-plus-keytruda-before-surgery-boosts-immune-response-in-breast-cancer/
5. “Radiation Plus Keytruda Before Surgery Boosts Immune Response in Breast Cancer,” by Russ Conroy. CURE; Dec. 11, 2025. https://www.curetoday.com/view/radiation-plus-keytruda-before-surgery-boosts-immune-response-in-breast-cancer

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