Alteration of the Tumor Microenvironment With Intratumoral Dendritic Cells Before Chemotherapy in ERBB2 Breast Cancer: A Nonrandomized Clinical Trial.

Importance: Current chemotherapy regimens for patients with ERBB2 (formerly HER2)-positive breast cancer are associated with considerable morbidity. These patients may benefit from more effective and less toxic therapies.

Objective: To evaluate the safety, immunogenicity, and preliminary efficacy of intratumoral (IT) delivery of conventional type 1 dendritic cells (cDC1) in combination with ERBB2-targeted therapies.

Pexidartinib and standard neoadjuvant therapy in the adaptively randomized I-SPY2 trial for early breast cancer.

Purpose: We investigated the small-molecule receptor tyrosine kinase-inhibitor of colony-stimulating factor-1 receptor pexidartinib in the stage II/III breast cancer in the I-SPY2 platform trial.

Methods: I-SPY2 is an adaptive platform trial that features multiple arms of experimental agents administered on a background of standard neoadjuvant therapy with paclitaxel and adriamycin/cyclophosphamide, followed by definitive surgery. The adaptive randomization engine preferentially assigns patients based upon cumulative performance of each agent in a given breast cancer subtype based on hormone receptor and HER2 receptor status.

Multi-institutional report of trastuzumab deruxtecan and stereotactic radiosurgery for HER2 positive and HER2-low breast cancer brain metastases.

Trastuzumab-deruxtecan (T-DXd) has demonstrated intracranial efficacy; however, safety and efficacy data remains limited with stereotactic radiosurgery (SRS). A multi-institutional review was performed with HER2+ or HER2-low metastatic breast cancer treated with T-DXd and SRS for active brain metastases. We identified 215 lesions treated over 48 SRS courses in 34 patients.

Gedatolisib in combination with palbociclib and endocrine therapy in women with hormone receptor-positive, HER2-negative advanced breast cancer: results from the dose expansion groups of an open-label, phase 1b study.

Background: The PI3K-mTOR pathway is frequently dysregulated in breast cancer. Combining an inhibitor targeting all class I PI3K isoforms and mTOR complex 1 (mTORC1)-mTOR complex 2 (mTORC2) with endocrine therapy and a CDK4/6 inhibitor might provide more effective tumour control than standard-of-care therapy. To evaluate this hypothesis, gedatolisib, a pan-PI3K-mTOR inhibitor, was assessed in a phase 1b trial combined with palbociclib and endocrine therapy in patients with hormone receptor-positive, HER2-negative, advanced breast cancer.

Veliparib with carboplatin and paclitaxel in BRCA-mutated advanced breast cancer (BROCADE3): Final overall survival results from a randomized phase 3 trial.

Background: In the BROCADE3 study, the addition of veliparib to carboplatin plus paclitaxel resulted in a significant improvement in progression-free survival (PFS) compared with placebo plus carboplatin and paclitaxel, in patients with germline BRCA1 or BRCA2 (BRCA1/2)-mutated, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. We now report final overall survival (OS) data.

Methods: BROCADE3 is a randomized phase 3 study that enrolled patients with BRCA1/2-mutated, HER2-negative advanced breast cancer who received ≤ 2 prior lines of chemotherapy for metastatic disease.

Race, Gene Expression Signatures, and Clinical Outcomes of Patients With High-Risk Early Breast Cancer.

Importance: There has been little consideration of genomic risk of recurrence by breast cancer subtype despite evidence of racial disparities in breast cancer outcomes.

Objective: To evaluate associations between clinical trial end points, namely pathologic complete response (pCR) and distant recurrence-free survival (DRFS), and race and examine whether gene expression signatures are associated with outcomes by race.

Design, Setting, And Participants: This retrospective cohort study used data from the Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis 2 (I-SPY 2) multicenter clinical trial of neoadjuvant chemotherapy with novel agents and combinations for patients with previously untreated stage II/III breast cancer.

Biological Synthesis of Copper Nanoparticles Using Edible Plant : Characterization of Antibacterial, Antioxidant, and Anti-Inflammatory Properties Using In Silico Molecular Docking Analysis.

This study prepared copper nanoparticles using an edible leaf extract from (AM-CuNPs) via eco-friendly green synthesis techniques. The size, shape, crystalline nature and functional groups of the synthesized AM-CuNP particles were analyzed by a UV-VIS spectrophotometer and SEM, EDX, TEM, XRD and FT-IR instrumentation. The synthesized AM-CuNPs had spherical shapes with sizes in the range of 30-80 nm and were crystalline in nature.

Investigating the Anti-Aging Effects of Caviar Oil on Human Skin.

Background/aim: As the largest organ of the human body, the skin serves as a critical barrier against environmental damage. However, many factors, such as genetics, sun exposure, and lifestyle choices can lead to skin damage creating wrinkles, sagging, and loss of elasticity. The use of skincare products containing natural ingredients has become increasingly popular as a way to combat the signs of aging.

Tucatinib and stereotactic radiosurgery in the management of HER2 positive breast cancer brain metastases.

Purpose: HER2-positive breast cancer has a high risk of brain metastasis. Stereotactic radiosurgery (SRS) is standard of care for limited brain metastases. Tucatinib, a HER2-targeted tyrosine kinase inhibitor, has demonstrated intracranial efficacy in the HER2-CLIMB Trial.

Early-Stage Triple-Negative Breast Cancer Journey: Beginning, End, and Everything in Between.

Triple-negative breast cancer (TNBC) is a very heterogeneous and aggressive breast cancer subtype with a high risk of mortality, even if diagnosed early. The mainstay of early-stage breast cancer includes systemic chemotherapy and surgery, with or without radiation therapy. More recently, immunotherapy is approved to treat TNBC, but managing immune-rated adverse events while balancing efficacy is a challenge.

A Gene Panel Associated With Abemaciclib Utility in -Mutated Breast Cancer After Prior Cyclin-Dependent Kinase 4/6-Inhibitor Progression.

Purpose: For patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC), first-line treatment is endocrine therapy (ET) plus cyclin-dependent kinase 4/6 inhibition (CDK4/6i). After disease progression, which often comes with resistance mutations (ESR1-MUT), which therapies to use next and for which patients are open questions. An active area of exploration is treatment with further CDK4/6i, particularly abemaciclib, which has distinct pharmacokinetic and pharmacodynamic properties compared with the other approved CDK4/6 inhibitors, palbociclib and ribociclib.

Pretherapy Ferumoxytol-enhanced MRI to Predict Response to Liposomal Irinotecan in Metastatic Breast Cancer.

Purpose To investigate ferumoxytol (FMX)-enhanced MRI as a pretreatment predictor of response to liposomal irinotecan (nal-IRI) for thoracoabdominal and brain metastases in women with metastatic breast cancer (mBC). Materials and Methods In this phase 1 expansion trial (ClinicalTrials.gov identifier, NCT01770353; 27 participants), 49 thoracoabdominal (19 participants; mean age, 48 years ± 11 [SD]) and 19 brain (seven participants; mean age, 54 years ± 8) metastases were analyzed on MR images acquired before, 1-4 hours after, and 16-24 hours after FMX administration.

Outcomes and clinicopathologic characteristics associated with disseminated tumor cells in bone marrow after neoadjuvant chemotherapy in high-risk early stage breast cancer: the I-SPY SURMOUNT study.

Purpose: Disseminated tumor cells (DTCs) expressing epithelial markers in the bone marrow are associated with recurrence and death, but little is known about risk factors predicting their occurrence. We detected EPCAM+/CD45- cells in bone marrow from early stage breast cancer patients after neoadjuvant chemotherapy (NAC) in the I-SPY 2 Trial and examined clinicopathologic factors and outcomes.

Methods: Patients who signed consent for SURMOUNT, a sub-study of the I-SPY 2 Trial (NCT01042379), had bone marrow collected after NAC at the time of surgery.

Safety and efficacy of HSP90 inhibitor ganetespib for neoadjuvant treatment of stage II/III breast cancer.

HSP90 inhibitors destabilize oncoproteins associated with cell cycle, angiogenesis, RAS-MAPK activity, histone modification, kinases and growth factors. We evaluated the HSP90-inhibitor ganetespib in combination with standard chemotherapy in patients with high-risk early-stage breast cancer. I-SPY2 is a multicenter, phase II adaptively randomized neoadjuvant (NAC) clinical trial enrolling patients with stage II-III breast cancer with tumors 2.

Intratumoral delivery of dendritic cells plus anti-HER2 therapy triggers both robust systemic antitumor immunity and complete regression in HER2 mammary carcinoma.

Background: Human epidermal growth factor receptor 2 (HER2) targeted antibodies in combination with chemotherapy has improved outcomes of HER2 positive (pos) breast cancer (BC) but toxicity of therapy remains a problem. High levels of tumor-infiltrating lymphocytes are associated with increased pathologic complete responses for patients treated with neoadjuvant therapy. Here we sought to investigate whether delivery of intratumoral (i.

The effects of wearing a face mask and of subsequent moisturizer use on the characteristics of sensitive skin.

Background: COVID-19 is a serious respiratory disease, and wearing masks has become essential in daily life. Nevertheless, the number of people complaining of skin problems caused by wearing masks is increasing. Therefore, we investigated the characteristics of changes in sensitive skin caused by wearing a mask.

Evolving management of HER2+ breast cancer brain metastases and leptomeningeal disease.

Patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer are at a particularly high risk of breast cancer brain metastasis (BCBM) and leptomeningeal disease (LMD). Improvements in systemic therapy have translated to improved survival for patients with HER2-positive BCBM and LMD. However, the optimal management of these cases is rapidly evolving and requires a multidisciplinary approach.

Nivolumab and Stereotactic Radiosurgery for Patients With Breast Cancer Brain Metastases: A Nonrandomized, Open-Label Phase 1b Study.

Purpose: We hypothesize treatment with nivolumab and stereotactic radiosurgery (SRS) will be feasible and well tolerated, and may improve intracranial tumor control rates compared with SRS alone.

Methods And Materials: The study was designed as a prospective, single-arm, nonrandomized, open-label, phase 1b trial of nivolumab and SRS among patients with metastatic breast cancer brain metastases. Key eligibility criteria included patients with breast cancer brain metastases of all subtypes, age ≥18, Eastern Cooperative Oncology Group Performance Status ≤2 with ≤10 brain metastases.

Safety and efficacy of veliparib plus carboplatin/paclitaxel in patients with HER2-negative metastatic or locally advanced breast cancer: subgroup analyses by germline / mutations and hormone receptor status from the phase-3 BROCADE3 trial.

Purpose: To evaluate efficacy and safety of veliparib combined with carboplatin/paclitaxel in patients with advanced human epidermal growth factor receptor 2 (HER2)-negative, germline (g)-associated breast cancer defined by hormone receptor (HR) and g/ mutation status.

Patients And Methods: In this phase-3, double-blind, placebo-controlled trial, patients ( = 509) with advanced HER2-negative breast cancer and g mutations were randomized 2:1 to receive veliparib plus carboplatin/paclitaxel or placebo plus carboplatin/paclitaxel. Patients who discontinued chemotherapy prior to disease progression continued receiving blinded veliparib/placebo monotherapy.

Trilaciclib Prior to Chemotherapy in Patients with Metastatic Triple-Negative Breast Cancer: Final Efficacy and Subgroup Analysis from a Randomized Phase II Study.

Purpose: We report final antitumor efficacy results from a phase II study of trilaciclib, an intravenous cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, administered prior to gemcitabine plus carboplatin (GCb) in patients with metastatic triple-negative breast cancer (NCT02978716).

Patients And Methods: Patients were randomized (1:1:1) to group 1 [GCb (days 1, 8); n = 34], group 2 [trilaciclib prior to GCb (days 1, 8); n = 33], or group 3 [trilaciclib (days 1, 8) and trilaciclib prior to GCb (days 2, 9); n = 35]. Subgroup analyses were performed according to CDK4/6 dependence, level of programmed death-ligand 1 (PD-L1) expression, and RNA-based immune signatures using proportional hazards regression.

Neoadjuvant T-DM1/pertuzumab and paclitaxel/trastuzumab/pertuzumab for HER2 breast cancer in the adaptively randomized I-SPY2 trial.

HER2-targeted therapy dramatically improves outcomes in early breast cancer. Here we report the results of two HER2-targeted combinations in the neoadjuvant I-SPY2 phase 2 adaptive platform trial for early breast cancer at high risk of recurrence: ado-trastuzumab emtansine plus pertuzumab (T-DM1/P) and paclitaxel, trastuzumab and pertuzumab (THP). Eligible women have >2.

The presentation of brain metastases in melanoma, non-small cell lung cancer, and breast cancer and potential implications for screening brain MRIs.

Purpose: This study assessed the presentation and institutional outcomes treating brain metastases (BM) of breast cancer (BC), non-small cell lung cancer (NSCLC), and melanoma origin.

Methods: Patients with brain metastases treated between 2014 and 2019 with primary melanoma, NSCLC, and BC were identified. Overall survival (OS) was calculated from dates of initial BM diagnosis using the Kaplan-Meier method.