MRI texture analysis in differentiating luminal A and luminal B breast cancer molecular subtypes - a feasibility study.

BACKGROUND: The aim of this study was to use texture analysis (TA) of breast magnetic resonance (MR) images to assist in differentiating estrogen receptor (ER) positive breast cancer molecular subtypes. METHODS: Twenty-seven patients with histopathologically proven invasive ductal breast cancer were selected in preliminary study. Tumors were classified into molecular subtypes: luminal A (ER-positive and/or progesterone receptor (PR)-positive, human epidermal growth factor receptor type 2 (HER2) -negative, proliferation marker Ki-67 < 20 and low grade (I)) and luminal B (ER-positive and/or PR-positive, HER2-positive or HER2-negative with high Ki-67 ≥ 20 and higher grade (II or III)). Co-occurrence matrix -based texture features were extracted from each tumor on T1-weighted non fat saturated pre- and postcontrast MR images using TA software MaZda. Texture parameters and tumour volumes were correlated with tumour prognostic factors. RESULTS: Textural differences were observed mainly in precontrast images. The two most discriminative texture parameters to differentiate luminal A and luminal B subtypes were sum entropy and sum variance (p = 0.003). The AUCs were 0.828 for sum entropy (p = 0.004), and 0.833 for sum variance (p = 0.003), and 0.878 for the model combining texture features sum entropy, sum variance (p = 0.001). In the LOOCV, the AUC for model combining features sum entropy and sum variance was 0.876. Sum entropy and sum variance showed positive correlation with higher Ki-67 index. Luminal B types were larger in volume and moderate correlation between larger tumour volume and higher Ki-67 index was also observed (r = 0.499, p = 0.008). CONCLUSIONS: Texture features which measure randomness, heterogeneity or smoothness and homogeneity may either directly or indirectly reflect underlying growth patterns of breast tumours. TA and volumetric analysis may provide a way to evaluate the biologic aggressiveness of breast tumours and provide aid in decisions regarding therapeutic efficacy.

Volumetric analysis of the terminal ductal lobular unit architecture and cell phenotypes in the human breast.

The major lactiferous ducts of the human breast branch out and end at terminal ductal lobular units (TDLUs). Despite their functional and clinical importance, the three-dimensional (3D) architecture of TDLUs has remained undetermined. Our quantitative and volumetric imaging of healthy human breast tissue demonstrates that highly branched TDLUs, which exhibit increased proliferation, are uncommon in the resting tissue regardless of donor age, parity, or hormonal contraception. Overall, TDLUs have a consistent shape and branch parameters, and they contain a main subtree that dominates in bifurcation events and exhibits a more duct-like keratin expression pattern. Simulation of TDLU branching morphogenesis in three dimensions suggests that evolutionarily conserved mechanisms regulate mammary gland branching in humans and mice despite their anatomical differences. In all, our data provide structural insight into 3D anatomy and branching of the human breast and exemplify the power of volumetric imaging in gaining a deeper understanding of breast biology.

Phase II study shows potential benefit of adenoviral vascular endothelial growth factor C (VEGF-C) and lymph node transfer in lymphedema.

BACKGROUND: Breast cancer-related lymphedema (BCRL) is a common complication lacking medical treatment. Lymfactin® is an adenovirus type 5-based gene therapy and prolymphangiogenic growth factor vector that induces vascular endothelial growth factor C (VEGF-C) expression. Our aim was to evaluate the therapeutic effect of Lymfactin® with vascularized lymph node transfer (VLNT). METHODS: This Phase II, double-blind, placebo-controlled, randomized multicenter study evaluated the efficacy and safety of Lymfactin® in combination with VLNT. The primary endpoints were edema volume, quality of life (LyQoLI), and lymphoscintigraphy. All adverse events were recorded. A mixed model of repeated measures analysis of covariance was performed. This study was a continuation of a previous Phase I Lymfactin® study. RESULTS: Thirty-nine patients with BCRL were recruited between June 2018 and December 2019 and randomized to receive either Lymfactin® (n = 20) or placebo (n = 19). The primary endpoints showed a positive effect of VLNT in both groups compared to the baseline, but without statistical differences between groups at 12 months. Additionally, greater improvements were observed in the tissue dielectric constant ratios measuring skin interstitial fluid levels in the Lymfactin® group compared to the placebo group (p = 0.020). No differences in adverse events were detected between the groups. CONCLUSIONS: This study was one of the few studies to objectively show a positive effect of VLNT in a prospective clinical multicenter setting. It was also the first-ever randomized prospective clinical study showing a quantitatively positive effect of a medical therapy on the edema of lymphedema although failing to show differences between groups in primary outcome measures.

Free latissimus dorsi perforator flap for reconstruction of hemifacial atrophy: case report.

Progressive hemifacial atrophy (PHA) is characterized by slow and progressive atrophy usually of one side of the face. PHA affects primarily the subcutaneous fat and muscle tissues, but may involve the bone. The cause is unknown. The treatment is symptomatic and directed at augmentation of the deficient soft-tissue volume. The reconstructive procedures may combine fat grafts, dermis fat grafts, pedicle flaps, bone grafts, microvascular free flaps, and alloplastic implants. We report a patient with of PHA whose condition was treated with a free latissimus dorsi (LD) perforator flap. The LD perforator flap was suitable for the large defect of the patient. It could easily be tailored and thinned to follow the facial contour. Minor revisions were needed for esthetic reasons. There was neither significant downward gravitation nor wasting of the flap. 23 months later, the natural appearance of the face was maintained.