Background: Controversy continues in the treatment of breast cancer in women over 70 years of age. In 2016, the Society of Surgical Oncology recommended against routine use of sentinel lymph node biopsy (SLNBx) as part of the ‘Choosing Wisely Campaign’. This study examines the oncologic safety of avoidance of routine SLNBx in patients over 70 years of age with invasive lobular carcinoma (ILC). Methods: The National Cancer Database was used to identify women with invasive ductal carcinoma (IDC) and ILC diagnosed between 2012 and 2020. Clinical and pathological staging, axillary staging, surgery type, and lymph node positivity between patients with IDC or ILC were compared. Results: Among women with T1 tumors, 85,949 (79.6%) patients with IDC and 12,761 (81.5%) patients with ILC underwent SLNBx (p < 0.001). Among patients who underwent SLNBx, those with IDC were more likely to have positive nodes (n = 7535, 8.8%) than those with ILC (n = 1041, 8.2%; p = 0.02). During the time interval of interest, for both IDC and ILC patients, the rate of axillary lymph node dissection decreased and rates of SLNBx or no axillary staging increased. On multivariate analysis, ILC histology was associated with use of SLNBx, but without nodal positivity. Conclusion: A trend de-escalation of axillary staging was identified in this study, however the majority of patients meeting the ‘Choosing Wisely’ criteria are still undergoing SLNBx. No increased risk of nodal positivity was identified among patients with ILC, suggesting that surgeons can continue to choose wisely and limit the use of SLNBx in women over 70 years of age with T1 ILC tumors.

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.

Adenovirus (Ad) is a widely studied viral vector for cancer therapy as it can be engineered to cause selective lysis of cancer cells. However, Ad delivery is limited in treating cancers that do not have coxsackievirus and adenovirus receptors (CAR). To overcome this challenge, Ad-encapsulated liposomes were developed that enhance the delivery of Ads and increase therapeutic efficacy. Cationic empty liposomes were manufactured first, to which an anionic Ad were added, which resulted in encapsulated Ad liposomes through charge interaction. Optimization of the liposome formula was carried out with series of formulation variables experiments using an extrusion process, which is ideal for laboratory-scale small batches. Later, the optimized formulation was manufactured with a homogenization technique—A high shear rotor-stator blending, that is ideal for large-scale manufacturing and is in compliance with Good Manufacturing Practices (GMP). Comparative in vitro transduction, physicochemical characterization, long-term storage stability at different temperature conditions, and in vivo animal studies were performed. Ad encapsulated liposomes transduced CAR deficient cells 100-fold more efficiently than the unencapsulated Ad (p ≤ 0.0001) in vitro, and 4-fold higher in tumors injected in nude mice in vivo. Both extrusion and homogenization performed similarly–with equivalent in vitro and in vivo transduction efficiencies, physicochemical characterization, and long-term storage stability. Thus, two Ad encapsulated liposomes preparation methods used herein, i.e., extrusion vs. homogenization were equivalent in terms of enhanced Ad performance and long-term storage stability; this will, hopefully, facilitate translation to the clinic.

Purpose of Review: Obtaining negative margins in breast conservation surgery continues to be a challenge. Re-excisions are difficult for patients and expensive for the health systems. This paper reviews the literature on current strategies and intraoperative clinical trials to reduce positive margin rates. Recent Findings: The best available data demonstrate that intraoperative imaging with ultrasound, intraoperative pathologic assessment such as frozen section, and cavity margins have been the most successful intraoperative strategies to reduce positive margins. Emerging technologies such as optical coherence tomography and fluorescent imaging need further study but may be important adjuncts. Summary: There are several proven strategies to reduce positive margin rates to < 10%. Surgeons should utilize best available resources within their institutions to produce the best outcomes for their patients.