Acute post-mastectomy pain is frequently challenging to adequately treat with local anesthetic-based regional anesthesia techniques due to its relatively long duration measured in multiple weeks. We report three cases in which preoperative ultrasound-guided percutaneous intercostal nerve cryoneurolysis was performed to treat pain following mastectomy. Across all postoperative days and all three patients, the mean pain score on the numeric rating scale was 0 for each day. Similarly, no patient required any supplemental opioid analgesics during the entire postoperative period; and, no patient reported insomnia or awakenings due to pain at any time point. This was a significant improvement over historic cohorts. Ultrasound-guided percutaneous cryoanalgesia is a potential novel analgesic modality for acute pain management which has a duration that better-matches mastectomy than other currently-described techniques. Appropriately powered randomized, controlled clinical trials are required to demonstrate and quantify both potential benefits and risks.

Purpose: The neutralizing peptibody trebananib prevents angiopoietin-1 and angiopoietin-2 from binding with Tie2 receptors, inhibiting angiogenesis and proliferation. Trebananib was combined with paclitaxel±trastuzumab in the I-SPY2 breast cancer trial. Patients and Methods: I-SPY2, a phase II neoadjuvant trial, adaptively randomizes patients with high-risk, early-stage breast cancer to one of several experimental therapies or control based on receptor subtypes as defined by hormone receptor (HR) and HER2 status and MammaPrint risk (MP1, MP2). The primary endpoint is pathologic complete response (pCR). A therapy “graduates” if/when it achieves 85% Bayesian probability of success in a phase III trial within a given subtype. Patients received weekly paclitaxel (plus trastuzumab if HER2-positive) without (control) or with weekly intravenous trebananib, followed by doxorubicin/cyclophosphamide and surgery. Pathway-specific biomarkers were assessed for response prediction. Results: There were 134 participants randomized to trebananib and 133 to control. Although trebananib did not graduate in any signature [phase III probabilities: Hazard ratio (HR)-negative (78%), HR-negative/HER2-positive (74%), HR-negative/HER2-negative (77%), and MP2 (79%)], it demonstrated high probability of superior pCR rates over control (92%–99%) among these subtypes. Trebananib improved 3-year event-free survival (HR 0.67), with no significant increase in adverse events. Activation levels of the Tie2 receptor and downstream signaling partners predicted trebananib response in HER2-positive disease; high expression of a CD8 T-cell gene signature predicted response in HR-negative/HER2-negative disease. Conclusions: The angiopoietin (Ang)/Tie2 axis inhibitor trebananib combined with standard neoadjuvant therapy increased estimated pCR rates across HR-negative and MP2 subtypes, with probabilities of superiority >90%. Further study of Ang/Tie2 receptor axis inhibitors in validated, biomarker-predicted sensitive subtypes is warranted.

Introduction: The use of opioids in mastectomy patients is a particular challenge, having to balance the management of acute pain while minimizing risks of continuous opioid use postoperatively. Despite attempts to decrease postmastectomy opioid use, including regional anesthetics, gabapentinoids, topical anesthetics, and nonopioid anesthesia, prolonged opioid use remains clinically significant among these patients. The goal of this study is to identify risk factors and develop machine-learning-based models to predict patients who are at higher risk for postoperative opioid use after mastectomy. Methods: In this retrospective cohort study, we collected data from patients that underwent mastectomy procedures. The primary outcome of interest was defined as oxycodone milligram equivalents (OME) greater than or equal to the 75% of OME use on a postoperative day 1. Model performance (area under the receiver-operating characteristics curve (AUC)) of various machine learning approaches was calculated via 10-fold cross-validation. Odds ratio (OR) and 95% confidence intervals (CI) were reported. Results: There were a total of 148 patients that underwent mastectomy and were included. The medium (quartiles) postoperative day 1 opioid use was 5 mg OME (0.25 mg OME). Using multivariable logistic regression, the most protective factors against higher opioid use was being postmenopausal (OR: 0.13, 95% CI: 0.03-0.61, p = 0.009) and cancer diagnosis (OR: 0.19, 95% CI: 0.05-0.73, p = 0.01). The AUC was 0.725 (95% CI: 0.572-0.876). There was no difference in the performance of other machine-learning-based approaches. Conclusions: The ability to predict patients’ postoperative pain could have a significant impact on preoperative counseling and patient satisfaction.

Diffusion-weighted MRI (DW-MRI) offers a potential adjunct to dynamic contrast-enhanced MRI to discriminate benign from malignant breast lesions by yielding quantitative information about tissue microstructure. Multi-component modeling of the DW-MRI signal over an extended b-value range (up to 3000 s/mm²) theoretically isolates the slowly diffusing (restricted) water component in tissues. Previously, a three-component restriction spectrum imaging (RSI) model demonstrated the ability to distinguish malignant lesions from healthy breast tissue. We further evaluated the utility of this three-component model to differentiate malignant from benign lesions and healthy tissue in 12 patients with known malignancy and synchronous pathology-proven benign lesions. The signal contributions from three distinct diffusion compartments were measured to generate parametric maps corresponding to diffusivity on a voxel-wise basis. The three-component model discriminated malignant from benign and healthy tissue, particularly using the restricted diffusion C₁ compartment and product of the restricted and intermediate diffusion compartments (C₁ and C₂). However, benign lesions and healthy tissue did not significantly differ in diffusion characteristics. Quantitative discrimination of these three tissue types (malignant, benign, and healthy) in non-pre-defined lesions may enhance the clinical utility of DW-MRI in reducing excessive biopsies and aiding in surveillance and surgical evaluation without repeated exposure to gadolinium contrast.