Ideal marker for targeted axillary dissection (IMTAD): a prospective multicentre trial.

BACKGROUND: Targeted axillary dissection (TAD) is an established method for axillary staging in patients with breast cancer after neoadjuvant chemotherapy (NAC). TAD consists of sentinel lymph node biopsy and initially pathological lymph node excision, which must be marked by a reliable marker before NAC. METHODS: The IMTAD study is a prospective multicentre trial comparing three localisation markers for lymph node localisation (clip + iodine seed, magnetic seed, carbon suspension) facilitating subsequent surgical excision in the form of TAD. The primary outcome was to prospectively compare the reliability, accuracy, and safety according to complication rate during marker implantation and detection and marker dislodgement. RESULTS: One hundred eighty-nine patients were included in the study-in 135 patients clip + iodine seed was used, in 30 patients magnetic seed and in 24 patients carbon suspension. The complication rate during the marker implantation and detection were not statistically significant between individual markers (p = 0.263; p = 0.117). Marker dislodgement was reported in 4 patients with clip + iodine seed localisation (3.0%), dislodgement did not occur in other localisation methods (p = 0.999). The false-negativity of sentinel lymph node (SLN) was observed in 8 patients, the false-negativity of targeted lymph nodes (TLN) wasn´t observed at all, the false-negativity rate (FNR) from the subcohort of ypN + patients for SLN is 9.6% and for TLN 0.0%. CONCLUSION: The IMTAD study indicated, that clip + iodine seed, magnetic seed and carbon suspension are statistically comparable in terms of complications during marker implantation and detection and marker dislodgement proving their safety, accuracy, and reliability in TAD. The study confirmed, that the FNR of the TLN was lower than the FNR of the SLN proving that the TLN is a better marker for axillary lymph node status after NAC. TRIAL REGISTRATION: NCT04580251. Name of registry: Clinicaltrials.gov. Date of registration: 8.10.2020.

Small non-coding RNA profiling in breast cancer: plasma U6 snRNA, miR-451a and miR-548b-5p as novel diagnostic and prognostic biomarkers.

BACKGROUND: Breast cancer is a leading cause of cancer-related death in women. Most cases are invasive ductal carcinomas of no special type (NST breast carcinomas). METHODS AND RESULTS: In this prospective, multicentric biomarker discovery study, we analyzed the expression of small non-coding RNAs (mainly microRNAs) in plasma by qPCR and evaluated their association with NST breast cancer. Large-scale expression profiling and subsequent validations have been performed in patient and control groups and compared with clinicopathological data. Small nuclear U6 snRNA, miR-548b-5p and miR-451a have been identified as candidate biomarkers. U6 snRNA was remarkably overexpressed in all the validations, miR-548b-5p levels were generally elevated and miR-451a expression was mostly downregulated in breast cancer groups. Combined U6 snRNA/miR-548b-5p signature demonstrated the best diagnostic performance based on the ROC curve analysis with AUC of 0.813, sensitivity 73.1% and specificity 82.6%. There was a trend towards increased expression of both miR-548b-5p and U6 snRNA in more advanced stages. Further, increased miR-548b-5p levels have been partially associated with higher grades, multifocality, Ki-67 positivity, and luminal B rather than luminal A samples. On the other hand, an association has been observed between high miR-451a expression and progesterone receptor positivity, lower grade, unifocal samples, Ki-67-negativity, luminal A rather than luminal B samples as well as improved progression-free survival and overall survival. CONCLUSIONS: Our results indicated that U6 snRNA and miR-548b-5p may have pro-oncogenic functions, while miR-451a may act as tumor suppressor in breast cancer.

Magnetic Seed (Magseed) Localisation in Breast Cancer Surgery: A Multicentre Clinical Trial.

INTRODUCTION: The aim of this study was to evaluate the accuracy and reliability of the Magseed magnetic marker in breast cancer surgery. METHODS: Thirty-nine patients with 41 implanted Magseeds undergoing surgical treatment in 3 surgical oncology departments were included in the retrospective trial to study pilot use of the Magseed magnetic marker in the Czech Republic for localisation of breast tumours or pathological axillary nodes in breast cancer patients. RESULTS: Thirty-four breast cancer and 7 pathological lymph node localisations were performed by Magseed implantation. No placement failures, or perioperative detection failures of Magseeds were observed (0/41, 0.0%), but one case of Magseed migration was present (1/41, 2.4%). All magnetic seeds were successfully retrieved (41/41, 100.0%). Negative margins were achieved in 29 of 34 (85.3%) breast tumour localisations by Magseed. CONCLUSION: Magseed is a reliable marker for breast tumour and pathological axillary node localisation in breast cancer patients. Magseed is comparable to conventional localisation methods in terms of oncosurgical radicality and safety.