miR-203 drives breast cancer cell differentiation.

A hallmark of many malignant tumors is dedifferentiated (immature) cells bearing slight or no resemblance to the normal cells from which the cancer originated. Tumor dedifferentiated cells exhibit a higher capacity to survive to chemo and radiotherapies and have the ability to incite tumor relapse. Inducing cancer cell differentiation would abolish their self-renewal and invasive capacity and could be combined with the current standard of care, especially in poorly differentiated and aggressive tumors (with worst prognosis). However, differentiation therapy is still in its early stages and the intrinsic complexity of solid tumor heterogeneity demands innovative approaches in order to be efficiently translated into the clinic. We demonstrate here that microRNA 203, a potent driver of differentiation in pluripotent stem cells (ESCs and iPSCs), promotes the differentiation of mammary gland tumor cells. Combining mouse in vivo approaches and both mouse and human-derived tridimensional organoid cultures, we report that miR-203 influences the self-renewal capacity, plasticity and differentiation potential of breast cancer cells and prevents tumor cell growth in vivo. Our work sheds light on differentiation-based antitumor therapies and offers miR-203 as a promising tool for directly confronting the tumor-maintaining and regeneration capability of cancer cells.

Evaluation of Axillary Lymph Node Marking with Magseed® before and after Neoadjuvant Systemic Therapy in Breast Cancer Patients: MAGNET Study.

Background: Due to the high false negative rate (FNR) associated with sentinel lymph node biopsy (SLNB) after neoadjuvant systemic therapy (NAST), the standard surgical treatment for patients with an initially positive axilla and indicated for NAST is axillary lymph node dissection (ALND). To avoid unnecessary ALND, this multicenter, prospective, observational study aimed to determine the effectiveness and ease of using magnetic seeds (Magseed®) for targeted axillary dissection (TAD) when the seeds are placed before or after NAST. Materials and Methods: We recruited 81 patients diagnosed with T1-T3 breast cancer, with clinically/radiologically positive nodal involvement (cN1, 75 patients with 1-3 nodes suspected nodes and 6 patients with up to 4 suspected nodes) prior to NAST. Positive nodes detected by fine-needle aspiration biopsy or core needle biopsy were marked with a stainless steel marker coil and after NAST with Magseed® prior to surgery (Post-NAST group), or directly with Magseed® before NAST (Pre-NAST group). The correlation between lymph nodes marked with Magseed® (MLNs) and sentinel lymph nodes (SLNs) was calculated based on pathologic assessment with the OSNA assay (Sysmex Corporation, Kobe) or conventional sectioning and staining techniques according to the standard protocols of each center. Results: All magnetic seeds were successfully identified and retrieved in just over 10 minutes of surgery, guided by the Sentimag® magnetometer system. The overall concordance rate between MLNs and SLNs was 81.5%, and the concordance between MLNs and SLNs with metastasis was 93.8%. Metastasis was detected in 54.3% of the MLNs compared with 48.1% of SLNs. In cases that presented negative MLN and negative SLN (negative TAD), the FNR was 0%. No significant differences were found between the Post-NAST and Pre-NAST groups. Conclusions: Our results validate the use of Magseed® for long-term marking of axillary lymph nodes and show that when used in combination with SLNB for TAD, a FNR of 0% can be achieved, avoiding unnecessary ALND.

Defining a Standardized Information Model for Multi-Source Representation of Breast Cancer Data.

This work aims to define a standardized information model for representation of multiple data sources in breast cancer. A set of data elements has been identified using ICHOM Breast Cancer as the minimum data set and adapting it to the needs of Hospital Universitario 12 de Octubre. With this, an information model has been defined according to ISO 13606 and SNOMED CT standards.