The second General Session at the 2025 San Antonio Breast Cancer Symposium® featured findings from clinical trials addressing de-escalation strategies, including potential omission of sentinel lymph node biopsy (SLNB) or preoperative breast magnetic resonance imaging (MRI) in certain patients. Presenters also shared data on a new preoperative targeted breast radiation approach for sensitizing tumors to immunotherapy.
A recording of the session, held Thursday, December 11, is available on demand for registered SABCS® 2025 participants through March 31, 2026, on the virtual meeting platform.
GS2-05: Primary Results from the Hormone Receptor (HR)-Positive/Human Epidermal Growth Factor Receptor 2 (HER2)-Negative 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
Preoperative radiation administered with pembrolizumab improved tumor T-cell infiltration in patients with node-positive higher-risk HR-positive, HER2-negative early-stage breast cancer, according to results from the phase II P-RAD clinical trial.
While immune checkpoint inhibitors (ICIs) have demonstrated promise in HR-positive, HER2-negative early-stage breast cancer in the CheckMate 7FL and KEYNOTE-756 trials, the pathologic complete response benefit of adding ICIs to neoadjuvant chemotherapy was specific to tumors with high stromal tumor-infiltrating lymphocytes or high PD-L1 at baseline, said presenter Gaorav Gupta, MD, PhD, Associate Professor of Radiation Oncology and Co-Leader of the Breast Cancer Research Program at the University of North Carolina Lineberger Comprehensive Cancer Center.
These data suggest that improving the immune-cell infiltration of these tumors before initiating chemoimmunotherapy may boost treatment response, he added.
P-RAD evaluated whether a new “immune priming” approach that focused radiation on the intact primary tumor — without impacting the lymph nodes — could enhance tumor immune-cell infiltration.
The 51 patients in P-RAD with node-positive HR-positive, HER2-negative breast cancer were randomly assigned 1:1:1 to receive neoadjuvant pembrolizumab with either no radiation, low-dose radiation (9 Gy), or high-dose radiation (24 Gy). All patients received subsequent pembrolizumab-based chemoimmunotherapy and definitive surgery.
T-cell infiltration at the time of a biopsy taken two weeks after radiation, the coprimary endpoint, was higher with preoperative high-dose radiation with pembrolizumab, compared with no or low-dose radiation with pembrolizumab.
While disease clearance in the lymph nodes was also higher with high-dose radiation and pembrolizumab, the study was not powered for comparative analysis of this coprimary endpoint.
Exploratory analyses suggested that preoperative high-dose radiation with pembrolizumab yielded greatest benefit in non-luminal A tumors with high PD-L1 expression.
“Future trials examining preoperative radiotherapy with pembrolizumab in HR-positive, HER2-negative breast cancer are needed to clarify disease control benefit,” Dr. Gupta concluded.
GS2-07: Effect of Preoperative Breast MRI Staging on Local Regional Recurrence (LRR) in Early-Stage Breast Cancer: Alliance A011104/ACRIN 6694
Patients with stage 1 or 2 HR-negative breast cancer without germline BRCA1/2 alterations had similar five-year locoregional recurrence rates whether or not they received preoperative breast MRI.
These findings from the phase III Alliance A011104/ACRIN 6694 clinical trial were presented by Isabelle Bedrosian, MD, the lead investigator of the study and a surgical oncologist and Professor of Breast Surgical Oncology at The University of Texas MD Anderson Cancer Center.
Dr. Bedrosian said that while MRI has been shown to be more sensitive for detecting disease compared with mammography, prospective trial data on the value of the MRI-based approach is sparse.
The A011104/ACRIN 6694 prospective trial tested whether MRI-based detection improves locoregional disease control.
The trial enrolled 319 patients with newly diagnosed stage 1 or 2 HR-negative breast cancer, a subset with a higher locoregional recurrence risk, who were eligible for BCS.
In both arms, a majority of patients had a single lesion and received neoadjuvant chemotherapy, and most had received a diagnostic ultrasound at baseline.
After a median follow-up of 61.1 months, similar proportions of patients in the MRI (93.2%) and non-MRI (95.7%) arms remained free of locoregional recurrence, with no statistically significant difference in locoregional recurrence rates.
Also, distant recurrence-free rates and overall survival did not differ between the MRI and non-MRI arms.
“There is great variability in the use of breast MRI across the U.S.,” Dr. Bedrosian said. “In my practice, we have not used MRI routinely, and this data would further reinforce our current practice, which is to be selective in the use of breast MRI [in the setting of stage 1 or 2 HR-negative breast cancer].”
GS2-11: Omission of sentinel lymph node biopsy in clinically T1-2 node-negative breast cancer patients treated with breast-conserving therapy: results of the Dutch BOOG 2013-08 randomized controlled trial after a median follow-up of five years
In patients with clinically node-negative, HR-positive, HER2-negative early-stage breast cancer, leaving out SLNB did not compromise regional disease control after a median follow-up of five years, according to findings from the BOOG 2013-08 phase III clinical trial.
Marjolein Smidt, MD, PhD, Professor at Maastricht University Medical Center, presented the data and said that previous studies have demonstrated the oncologic safety of surgical de-escalation from axillary lymph node dissection to SLNB in clinically node-negative breast cancer.
The BOOG 2013-08 trial assessed whether omitting SLNB in clinically node-negative patients with early-stage tumors undergoing BCS and whole-breast radiotherapy impacted regional recurrence-free survival (RRFS).
In the study, 1,733 patients with clinically node-negative, HR-positive, HER2-negative early-stage tumors were randomly assigned to either undergo or forgo SLNB.
At a median five-year follow-up, in 1,574 evaluable patients, cancer recurrence in the lymph nodes surrounding the primary tumor occurred in 0.5% of patients who underwent SLNB, compared with 1.2% in the no-SLNB arm — a difference that was not statistically significant. The median five-year RRFS was also not significantly different between arms — 96.6% with SLNB vs. 94.2% without SLNB.
Dr. Smidt said that based on these data, “SLNB omission may be safely considered in these patients,” the majority of whom were older than 50 years and had HR-positive HER2-negative, grade 1−2, T1 tumors.
Additional abstracts presented during Thursday’s General Session 2 included:
GS2-01: More versus less invasive axillary surgical staging procedures in breast cancer patients converting from a clinically node-positive to a clinically node-negative stage through neoadjuvant chemotherapy – primary endpoint analysis of the international prospective multicenter AXSANA/EUBREAST 3(R) study
GS2-02: Axillary surgery in breast cancer patients with one to three sentinel node macrometastases and breast-conserving therapy: Secondary results of the INSEMA trial
GS2-03: Insights of applied radiotherapy among patients undergoing breast-conserving surgery with or without axillary sentinel lymph node biopsy: secondary results from the INSEMA trial
GS2-04: Heating up cold tumors: single-cell mapping of immune and adenosine pathway reprogramming in luminal B breast cancer (Neo-CheckRay trial)
GS2-09: The single-arm confirmatory trial of tamoxifen alone without surgery for low-risk DCIS of the breast with ER-positive HER2-negative (LORETTA trial: JCOG1505)
GS2-12: Radiation doses and fractionation schedules in non-low-risk ductal carcinoma in situ in the breast (BIG 3-07/TROG 07.01): final 10-year analysis of a randomized, factorial, multicenter, open-label, phase III study
