Recent trials such as INSEMA and SOUND have demonstrated the oncological safety of omitting sentinel lymph node biopsy in selected patients with hormone receptor-positive, HER2-negative early breast cancer. However, the implications for adjuvant treatment decisions in routine clinical practice remain unclear. We conducted a retrospective multicenter cohort study from university breast cancer centers, analyzing 867 patients diagnosed between 2020 and 2024 who met INSEMA criteria: cT1, G1-2, age ≥50 years, clinically node-negative, undergoing breast-conserving surgery. We evaluated the incidence of pathologically positive lymph nodes, frequency of postoperative upgrades in tumor stage or grading, and potential impact on adjuvant therapy decisions, including indications for CDK4/6 inhibitors, secondary axillary surgery or radiation. Sentinel lymph node biopsy revealed occult lymph node metastases in 14.3 % (n = 124) of patients, with a false-negative rate of 10.5 % when micrometastases and isolated tumor cells were excluded. In 11.6 % of cases, nodal positivity led to relevant therapeutic changes, including chemotherapy, axillary radiation, or potential adjuvant CDK4/6 inhibitor therapy. Moreover, 18.8 % of patients would have required secondary axillary surgery due to postoperative upgrades in tumor characteristics. The number needed to operate to prevent one invasive recurrence with CDK4/6 inhibitors varies significantly based on age and clinical tumor size, ranging from 1:333 (maximum) to 1:111 (minimum). While omission of sentinel lymph node biopsy appears safe in selected patients, our real-world data suggest that axillary staging retains clinical relevance for guiding personalized treatment, unless other prognostic tests like gene expression profiles are used.

De-escalation is currently taking place in both the surgical and systemic treatment of breast cancer. The introduction of trastuzumab, the first monoclonal antibody against the HER2 receptor, over 20 years ago was a milestone in the treatment of HER2-positive breast cancer and marked the beginning of a new era in targeted tumor therapy. In the sense of de-escalation, omitting non-targeted cytotoxic chemotherapy altogether is often hailed as the ultimate goal of oncological research. Especially in cases of small, node-negative, HER2-positive early breast cancer, it remains a challenge for clinicians to establish the safest and most efficient treatment plan while considering the significant potential for toxic side effects associated with chemotherapy and HER2-targeted therapy, and the generally excellent prognosis. In this context, several ongoing studies are currently assessing chemotherapy-free regimens as part of strategies aimed at de-escalating therapy in the field of HER2-positive early breast cancer. Despite the promising early results of these studies, the combination of anti-HER2 treatment with a chemotherapy backbone remains the standard of care.

Background/Objectives: This single-center analysis evaluated the number of potential candidates for endocrine-based oral maintenance therapy in a real-world setting, focusing on three therapeutic agents, namely, olaparib, abemaciclib, and ribociclib, for patients with hormone receptor-positive HER2-negative early breast cancer. Methods: All breast cancer cases from the past 10 years (n = 3230) that underwent treatment at the certified Breast Cancer Center of the Department of Gynecology and Obstetrics, University Hospital Schleswig-Holstein, Lübeck Campus, were analyzed. Results: Of a total of 2038 patients with HR+ HER2− eBC, 685 patients (33.6%) qualified for one or more of the three agents—olaparib, abemaciclib, and ribociclib. Of these 685 patients, 523 patients (76.4%) had node-positive and 162 (23.6%) node-negative disease. Moreover, 368 patients (18.1% of a total of 2038 patients with HR+ HER2− eBC) were eligible exclusively for ribociclib, including all node-negative patients. A total of 141 patients (6.9%) met the criteria for all three agents. In contrast, 1353 patients (66.4%) had no indication for combined endocrine therapy. Conclusions: To our knowledge, this is the largest analysis addressing all three therapeutic strategies for combined endocrine therapy. The broad indication criteria of the NATALEE study may increase clinic workloads due to more frequent physician/patient interactions. It also remains unclear how therapy recommendations will influence actual treatment, as increased visits and potential side effects could affect patient compliance and adherence.

Background: Up to 60% of breast cancer patients achieve pathological complete response (pCR) and factors associated with breast pCR have been extensively investigated. In patients with initially node-positive disease predicting axillary response to treatment remains challenging. Our study examines a biomarker panel assessed on core-biopsy lymph-node metastatic tissue with the goal to establish predictive markers for nodal positive breast cancer. Materials and methods: Forty women with core biopsy-proven node-positive breast cancer scheduled to receive neoadjuvant treatment at the certified Breast Cancer Center of the University Hospital Schleswig–Holstein Campus Lübeck were included. The expressions of CAIX, PD-L1, TROP2, MSH2, MSH6, MLH1, and PMS2 as well as p53 mutation were assessed. Biomarkers were chosen based on their association with tumorigenesis and tumor progression. Statistical analysis was performed using SPSS 29. This investigator-initiated study was supported by a research grant from Gilead (Gilead Förderprogramm). Results: Higher CAIX levels were associated with triple-negative and Her2-positive receptor status ( p = 0.003), Ki67 ≥ 50% in breast core biopsy ( p = 0.005), as well as postmenopausal status ( p = 0.007). P53 mutation was more frequent in G3 tumors ( p = 0.025). All lymph-node metastases were microsatellite stable (MSS). None of the markers could significantly predict pathological response (complete, breast, or nodal). Conclusion: Our study shows upregulated CAIX in lymph-node metastasis frequently occurs in aggressive and highly proliferative tumors. However, none of the examined biomarkers could predict nodal response to therapy. Further research is necessary to better identify patients most likely to achieve nodal response through neoadjuvant chemotherapy.