Less Intensive Surgical Staging Shows Noninferiority in Breast Cancer Trial

"In univariate analyses, high risk in the [ALND] group translated into statistically significant, more distant recurrences into marginally significant, more invasive breast cancer events in a trend toward worse [OS], but it did not translate into more axillary recurrences, regional recurrences, or local regional recurrences," according to study investigator Thorsten Kühn, MD, PhD.

Data from the observational study AXSANA/EUBREAST 3(R) (NCT04373655) demonstrated noninferior, comparable outcomes with less invasive surgical staging strategies vs axillary lymph node dissection (ALND) among patients with breast cancer who converted from clinically node-positive (cN+) to node-negative (ycN0) status after neoadjuvant chemotherapy (NACT), according to a presentation at the 2025 San Antonio Breast Cancer Symposium (SABCS).1

Results of the study’s first primary end point analysis were shared by Thorsten Kühn, MD, PhD, head of the AXSANA study. Kühn is also a senior physician at the department of Gynecology and Obstetrics at the University of Ulm and head of the Interdisciplinary Breast Center of The Filder Clinic in Germany.

The analysis detailed 3-year data for the study’s co-primary end point of axillary recurrence-free survival (ARFS) for over 2500 patients who had undergone either ALND or less invasive procedures including targeted axillary dissection (TAD), sentinel lymph node biopsy (SLNB), and targeted lymph node biopsy (TLNB) as first surgery.

Key Finding: Less Invasive Procedures Noninferior to ALND

At 3 years, the respective ARFS after ALND and TAD/SLNB/TLNB were 99.2% (95% CI, 98.2%-100.0%) and 98.8% (95% CI, 98.1%-99.5%), showing low rates of axillary recurrence with both procedures.

Crucially, the analysis demonstrated that less invasive procedures like TAD/SLNB/TLNB are noninferior to ALND in terms of axillary recurrence based on the lower bound of a 90% confidence interval around 3-year ARFS. With a 98.2% lower bound exceeding the noninferiority criterion of 97%, the study’s primary end point had been met.

These data confirm the strong oncologic outcomes of less invasive procedures and noninferiority to ALND, the historic standard of care that has been associated with high morbidity. The findings support the use of these procedures as staging tools for patients converting from node positivity to negativity under chemotherapy—regardless of initial tumor stage or subtype—potentially minimizing surgical morbidities and ultimately enhancing patient quality of life without compromising clinical benefit.

Additional Interim Data: Recurrence and Survival

Interim analysis data of other oncologic end points, including local- and regional-distant recurrence–free survival, breast cancer–specific survival, and overall survival (OS), were also reported during the presentation.

On univariate Cox regression, the hazard ratio (HR) for distant recurrence comparing ALND vs TAD/SLNB/TLNB was 1.41 (95% CI, 1.05-1.90). Kühn also called attention to the HRs for invasive breast cancer recurrence (1.30; 95% CI, 0.99-1.71) and OS (1.35; 95% CI, 0.89-2.04).

“In univariate analyses, high risk in the [ALND] group translated into statistically significant, more distant recurrences into marginally significant, more invasive breast cancer events in a trend toward worse [OS], but it did not translate into more axillary recurrences, regional recurrences, or local regional recurrences,” commented Kühn on the data.

To explain the observations in the univariate analyses, Kühn revisited the observed baseline differences in risk between the groups. “Patients who underwent [ALND] had a higher initial risk in terms of T stage, a higher nodal burden, had more mastectomies, more axillary radiotherapy, and more patients had residual disease,” he noted.

Upon adjustment for these factors in multivariate analyses, the differences in the univariate analysis disappeared. These adjusted interim findings suggest that the 2 procedures yield comparable results regarding these end points after accounting for patient factors.

“Further follow-up is necessary to assess long-term results and the effect of differences in staging accuracy on breast cancer-specific survival and [OS],” said Kühn on next steps.1

AXSANA Study: Background and Patient Characteristics

The ongoing AXSANA study is a large, global, prospective cohort study launched by the European Breast Cancer Research Association of Surgical Trialists (EUBREAST) that set out to solidify the evidence base for guideline recommendations regarding axillary staging techniques, specifically among those who initially present with cN+ and later convert to ycN0 following NACT.2 Although axillary dissection is increasingly shifting toward less invasive procedures, investigators cite discordant national and institutional treatment standards for this patient group, with some moving to recommend less invasive procedures, while others continue to recommend ALND.

To that end, the study is evaluating the comparative oncologic outcomes of different axillary surgical staging procedures used with patients according to institutional and national guidelines. Specifically, the study is measuring co-primary end points of ARFS, iBCSS, patient-reported quality of life, and arm morbidity. Recruitment for the study is ongoing, with estimated study completion in 2030.

Between June 2020 and April 2025, there were 6474 patients with breast cancer enrolled in the study across 288 global sites. The present analysis included the 2632 patients who had completed first surgery by December 31, 2023. For the primary staging procedure, most (69.6%) had undergone less invasive procedures including TAD (n = 1399), SLNB (n = 419), and TLNB (n = 15), while 30.4% had undergone ALND. A majority (94.6%) of patients received post-NACT nodal radiotherapy.

DISCLOSURES: Kühn declared receiving honoraria from MSD, Exact Sciences, Novartis, Lilly, Merit Medical, Sirius Pintuition, Endomag, and Daiichi Sankyo, and grant/research support from Claudia von Schilling Foundation for Breast Cancer Research, Ehmann Foundation Savognin, and Eugen & Irmgard Hahn Foundation.

References

1. Kühn, T, Banys-Paluchowski M, Ditsch N, et al. 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. Presented at: 2025 San Antonio Breast Cancer Symposium; December 9–12, 2025; San Antonio, Texas. Abstract GS2-01.
2. AXillary Surgery After NeoAdjuvant Treatment (AXSANA). ClinicalTrials.gov. Updated March 3, 2025. Accessed December 10, 2025. https://www.clinicaltrials.gov/study/NCT04373655