Meet us at this year's San Antonio Breast Cancer Symposium (SABCS)

Summary of SABCS 2025 Highlights

The San Antonio Breast Cancer Symposium 2025 showcased groundbreaking results from clinical trials and translational research. Here are the key takeaways from our contributions:

1️⃣ Prognostic Impact of TILs & Ki67 in Residual Tumors in TNBC 

This large pooled analysis of nine neoadjuvant trials (GeparTrio, GeparQuattro, GeparQuinto, GeparSixto, GeparSepto, GeparOcto, GeparNuevo, GeparX, and GeparOla) shows that simple, routinely available biomarkers in residual TNBC—Ki67 and tumor-infiltrating lymphocytes—provide powerful prognostic information beyond pCR status alone. Patients with low Ki67 and high TILs in residual disease had markedly better long-term survival, while those with high Ki67 and low TILs faced a more than sevenfold higher risk of death, supporting the use of these markers to better personalize post-neoadjuvant treatment decisions.

2️⃣ Pooled Analysis of Carboplatin Effect 

This pooled analysis of three randomized trials (GeparSixto, BrighTNess, CALGB 40603) confirms that adding neoadjuvant carboplatin significantly increases pathologic complete response rates and improves event-free survival in early-stage triple-negative breast cancer, reinforcing its role as a key component of modern neoadjuvant therapy. While no overall survival benefit was observed and no predictive biomarker for carboplatin benefit was identified, the strong prognostic value of immune gene expression signatures highlights the clinical importance of the tumor immune microenvironment and supports ongoing efforts to better personalize treatment intensity.

3️⃣ GeparDouze Ovarian Substudy 

This first-of-its-kind analysis from a randomized trial shows that adding the checkpoint inhibitor atezolizumab to standard neoadjuvant chemotherapy for early triple-negative breast cancer may increase the risk of both short- and long-term ovarian dysfunction in young women, with higher rates of persistent chemotherapy-induced ovarian failure observed up to two years after treatment. These findings support more informed fertility counseling and shared decision-making for younger patients considering immunotherapy-containing regimens.

4️⃣ GeparDouze Study Gene Expression Analysis

This first comprehensive biomarker analysis from the NSABP B-59/GeparDouze trial demonstrates that high tumor-infiltrating lymphocytes (≥30%) and immune-activated TNBC subtypes are strongly associated with improved pathologic complete response and event-free survival in patients receiving neoadjuvant immune-chemotherapy. Importantly, the survival benefit from adding atezolizumab was concentrated in immune-activated tumors, highlighting the clinical value of TIL levels and molecular subtyping as accessible biomarkers to better select patients most likely to benefit from immunotherapy in early TNBC.

5️⃣ INSEMA Study – Secondary Results on Completion Axillary Dissection

Results from the second randomization of the INSEMA trial show that in patients with 1–3 positive sentinel lymph nodes, omission of completion axillary lymph node dissection did not demonstrate non-inferiority for invasive disease-free survival, with numerically lower 5-year invasive disease-free survival compared with completion axillary lymph node dissection. While overall survival and locoregional recurrence rates remained similar between arms—supporting prior de-escalation data—these findings underscore the need for careful patient selection and longer follow-up when considering further axillary surgery reduction.

6️⃣ INSEMA Study – Secondary Results Radiotherapy Analysis

This radiotherapy analysis from the INSEMA trial shows that omission of sentinel lymph node biopsy was not compensated by escalated axillary radiotherapy, despite slightly higher incidental axillary doses and more frequent regional nodal irradiation in the SLNB arm. Importantly, radiotherapy techniques and outcomes remained comparable between groups, supporting the clinical safety and feasibility of omitting sentinel lymph node biopsy without requiring escalation of axillary radiation in breast-conserving surgery.

7️⃣ On-treatment Biopsies: Longitudinal TiLs and Ki67 

This pooled analysis of on-treatment biopsies across multiple neoadjuvant trials (GeparSixto, GeparSepto, GeparNuevo, GeparX, and GeparOla) shows that early persistence of residual invasive cancer after just 2–4 treatment cycles strongly predicts failure to achieve pCR and is associated with significantly worse disease-free and overall survival. These findings highlight on-treatment biopsies as a powerful, early-response tool that could enable real-time treatment adaptation, helping clinicians identify patients unlikely to benefit from ongoing therapy and opening the door to more personalized neoadjuvant strategies.

8️⃣ Impact of NACT on Bone Metabolism Measured by Calcium Isotope Ratios – GeparX Study

This first-of-its-kind analysis from the GeparX trial shows that neoadjuvant chemotherapy leads to measurable bone calcium loss in postmenopausal women with early breast cancer, while concurrent denosumab not only prevents this loss but promotes net bone mineralization. These findings highlight a clinically meaningful supportive care benefit of denosumab and position the Calcium Isotope Method (CIM) serum levels as a simple, accessible biomarker to monitor bone health and guide early intervention during systemic therapy.

 🎉 A heartfelt thank you to all patients, families, researchers, and sponsors who made these advancements possible. Together, we are shaping the future of breast cancer research!