Toralf Reimer

PURPOSE: Surgical axillary staging in patients with node-positive breast cancer (BC) who converted to clinical node negativity through neoadjuvant chemotherapy (NACT) has changed significantly in recent years. Targeted axillary dissection (TAD) and target lymph node (TLN) biopsy (TLNB) became increasingly popular. However, data comparing marking techniques for the TLN are limited. Here, we evaluate marking techniques in the largest prospective cohort worldwide. MATERIALS AND METHODS: Among patients from the ongoing prospective multicenter AXSANA (EUBREAST-03) study who received TLN marking and TAD/TLNB, we evaluated different marking methods with respect to detection and removal rates and clinical performance. RESULTS: Until January 6, 2025, 6,129 patients from 26 countries were enrolled. Of these patients, 2,596 had ≥1 TLN marked before NACT and completed surgery; 13.3% of the patients had ≥4 suspicious nodes at diagnosis. Pre-NACT TLN marking used a clip in 2,003 patients (77.2%), magnetic seed in 287 (11.1%), carbon ink in 192 (7.4%), radar marker in 119 (4.6%), radioactive seed in 18 (0.7%), radiofrequency identification device (RFID) in 12 (0.5%), or other methods in two (0.1%). One TLN was marked in 2,427 patients (93.5%), two TLNs in 138 (5.3%), and ≥3 in 27 patients (1%). Targeted removal of the TLN was planned in 2,100 patients (80.9%; TAD in 2,076 [80.0%] and TLNB in 24 [0.9%]). The TLN was detected and removed by TAD/TLNB in 1,915 patients (91.2%). TLN detection rate was the highest in patients whose TLNs were marked pre-NACT with markers suitable for probe-guided detection (96.6%; radioactive seed: 100%, magnetic seed: 96.9%, radar marker: 96.1%, RFID: 90%), followed by carbon ink (94.9%) and clip (89.6%; P < .001). CONCLUSION: This large prospective analysis of patients with initially clinically node-positive BC receiving NACT demonstrates that probe-guided detection markers used to mark metastatic nodes before NACT provide superior detection rates.

The sub-study of the INSEMA trial (randomization-2) compares completion axillary lymph node dissection (cALND) with sentinel lymph node biopsy (SLNB) alone in cN0 patients with T1/T2 invasive breast cancer and one to three sentinel node macrometastases undergoing upfront breast-conserving surgery. The key secondary objective is to assess whether the SLNB-alone arm is non-inferior to cALND in terms of invasive disease-free survival (iDFS). Finally, 485 patients were recruited, and 386 patients (cALND: N = 169, SLNB alone: N = 217) were included in the per-protocol set. The median follow-up is 74.2 months. The 5-year iDFS analysis in the per-protocol set demonstrates a non-significant difference between study arms, with a hazard ratio (HR) of 1.69 (95% CI: 0.98-2.94) for SLNB alone compared to cALND. The 5-year iDFS rates are 86.6% (81.0%-90.7%) in the SLNB-alone arm and 93.8% (88.7%-96.6%) in the cALND arm ( P = 0.058). The 5-year overall survival rates are 94.9% (90.6%-97.2%) in the SLNB-alone arm and 96.2% (91.7%-98.3%) in the cALND arm ( P = 0.663). Locoregional recurrences (LRR) were infrequent, with 5-year incidence rates of 1.1% versus 0.0% ( P = 0.405) in the SLNB-alone arm compared to cALND. In summary, no significant differences were observed between SLNB alone versus cALND for iDFS, overall survival, and LRR. Trial registration number: NCT02466737

Background: For the application of mesenchymal stem cells (MSCs) in regenerative medicine, xeno‐free ex vivo cultivation is necessary. Therefore, this study aimed to investigate whether adipose‐derived stem cells (ADSCs) from human breast tissue could be cultivated with human platelet lysate (hPL)—a promising alternative derived from human platelets—instead of fetal bovine serum (FBS). Methods: The influence of hPL within the culture medium of ADSCs from the female breast was analyzed regarding immunophenotype, adipogenic differentiation capacity, growth kinetics, and cell cycle distribution of ADSCs. Subsequently, the formation of spheres in hPL‐supplemented medium was characterized in detail. Results: In comparison to FBS, the supplementation of medium with hPL resulted in a change in morphology, but the immunophenotype remained unchanged. Furthermore, supplementation of the medium with hPL caused an improved adipogenic differentiation capacity, increased growth, and shortened population doubling time (PDT) in ADSCs. Additionally, the cultivation of ADSCs with hPL led to spontaneous formation of spheres. Conclusion: hPL is not only a replacement for the ethically controversial cell culture additive FBS but also offers a xeno‐free method for the cultivation of breast tissue‐derived ADSCs and thus represents an important step from bench to bedside.

Supplementary Table 4 shows associations between the genes in ER signaling signature and iDFS

Supplementary Table 2 shows a comparison of patient characteristics between subjects with and without BC360 and all patients in the trial

Supplementary Table 5 shows association between median sTIL levels and pCR, iDFS and OS

Supplementary Figure 3 shows association between RNA signatures and overall survival

Supplementary Table 3 shows associations between the genes in ER signaling signature and pCR