A PROTAC degrader suppresses oncogenic functions of PTK6 inducing apoptosis of breast cancer cells.

Protein tyrosine kinase 6 (PTK6), a non-receptor tyrosine kinase, is an oncogenic driver in many tumor types. However, agents that therapeutically target PTK6 are lacking. Although several PTK6 kinase inhibitors have been developed, none have been clinically translated, which may be due to kinase-independent functions that compromise their efficacy.

MARCH2, a Novel Oncogene-regulated SNAIL E3 Ligase, Suppresses Triple-negative Breast Cancer Metastases.

Unlabelled: Epithelial-mesenchymal transition (EMT) in cancer promotes metastasis and chemotherapy resistance. A subset of triple-negative breast cancer (TNBC) exhibits a mesenchymal gene signature that is associated with poor patient outcomes. We previously identified PTK6 tyrosine kinase as an oncogenic driver of EMT in a subset of TNBC.

Impact of Preoperative Extramammary Findings in Patients with Newly Diagnosed Breast Cancer.

Background: Breast MRI has been associated with significant rates of false positive findings. We aimed to determine the frequency of extramammary findings (EMFs) in newly diagnosed breast cancer patients on breast MRI with contrast and assess the significance of these findings and need for additional imaging and follow-up.

Study Design: A retrospective review of patients diagnosed with breast cancer from October 2018 to October 2019 was performed.

Thoracoscopy versus thoracotomy for esophageal atresia and tracheoesophageal fistula: Outcomes from the Midwest Pediatric Surgery Consortium.

Background/purpose: Controversy persists regarding the ideal surgical approach for repair of esophageal atresia with tracheoesophageal fistula (EA/TEF). We examined complications and outcomes of infants undergoing thoracoscopy and thoracotomy for repair of Type C EA/TEF using propensity score-based overlap weights to minimize the effects of selection bias.

Methods: Secondary analysis of two databases from multicenter retrospective and prospective studies examining outcomes of infants with proximal EA and distal TEF who underwent repair at 11 institutions was performed based on surgical approach.

Insulin resistance and racial disparities in breast cancer prognosis: a multi-center cohort study.

The survival for breast cancer (BC) is improving but remains lower in Black women than White women. A number of factors potentially drive the racial differences in BC outcomes. The aim of our study was to determine if insulin resistance (defined as homeostatic model assessment for insulin resistance (HOMA-IR)), mediated part of the relationship between race and BC prognosis (defined by the improved Nottingham prognostic index (iNPI)).

Disparities in the Management of Pediatric Breast Masses.

Introduction: Disparities in surgical management have been documented across a range of disease processes. The objective of this study was to investigate sociodemographic disparities in young females undergoing excision of a breast mass.

Methods: A retrospective study of females aged 10-21 y who underwent surgery for a breast lesion across eleven pediatric hospitals from 2011 to 2016 was performed.

Racial Disparities in Time to Treatment Persist in the Setting of a Comprehensive Breast Center.

Background: Racial disparities in breast cancer care have been linked to treatment delays. We explored whether receiving care at a comprehensive breast center could mitigate disparities in time to treatment.

Methods: Retrospective chart review identified breast cancer patients who underwent surgery from 2012 to 2018 at a comprehensive breast center.

Impact of Screening Mammography on Treatment in Young Women Diagnosed with Breast Cancer.

Background: There is little data exploring the impact of screening mammography on subsequent treatment in the 40-49-year age group with breast cancer. We sought to assess the association between frequency of mammography in young women and extent of surgery and chemotherapy required.

Methods: An IRB-approved retrospective review was performed of patients diagnosed with breast cancer between ages 40 and 49 years from 1 January 2010 to 19 November 2018 within a single health system.

Choice of Mastectomy May Increase the Extent of Axillary Surgery in Women with Breast Cancer.

Introduction: Based on the ACOSOG Z0011 trial, women who undergo breast conservation therapy (BCT) and have limited disease in the axilla on sentinel lymph node (SLN) biopsy do not require axillary lymph node dissection (ALND). In this study we investigate the incidence of ALND in patients undergoing elective mastectomy with limited disease in the axilla to identify how many women may have been spared additional axillary surgery if they chose BCT.

Methods: All women with invasive breast cancer treated at a single tertiary care breast center from 2010-2018 who were candidates for BCT but elected mastectomy and underwent SLN biopsy were identified through retrospective review of a prospectively maintained database.

Mastectomy or Margin Re-excision? A Nomogram for Close/Positive Margins After Lumpectomy for DCIS.

Background: Anatomic extent of ductal carcinoma in situ (DCIS) may be uncertain in spite of clinical, pathologic, and imaging data. Consequently close/positive margins are common with lumpectomy for DCIS and often lead to a challenge in deciding whether to perform a re-excision or mastectomy.

Patients And Methods: From a single health system, we identified cases of lumpectomy for DCIS with close/positive margins who underwent re-excision for the purpose of constructing a nomogram.

CALGB 40603 (Alliance): Long-Term Outcomes and Genomic Correlates of Response and Survival After Neoadjuvant Chemotherapy With or Without Carboplatin and Bevacizumab in Triple-Negative Breast Cancer.

Purpose: CALGB 40603 (NCT00861705), a 2 × 2 randomized phase II trial, demonstrated that adding carboplatin or bevacizumab to weekly paclitaxel (wP) followed by doxorubicin and cyclophosphamide significantly increased the pathologic complete response (pCR) rate in stage II-III triple-negative breast cancer. We now report long-term outcomes (LTOs) and correlative science end points.

Patients And Methods: The Kaplan-Meier method was used to estimate LTOs in 443 patients who initiated study treatment.

Does previous history of cancer or atypia predict histologic upgrade for pure intraductal papillomas diagnosed via core biopsy? A study of 490 cases at a single institution.

Background: Management of pure intraductal papillomas (IDP) without atypia diagnosed on core needle biopsy (CNB) remains controversial given highly variable rates of upgrade in the literature.

Aim: We sought to identify clinical and histologic factors that predict upgrade to atypia or malignancy in a large population.

Methods And Results: A retrospective review was performed of all cases of pure IDP diagnosed on CNB and then surgically excised at a single institution from 2008 to 2018.

Simultaneous CK2/TNIK/DYRK1 inhibition by 108600 suppresses triple negative breast cancer stem cells and chemotherapy-resistant disease.

Triple negative breast cancer (TNBC) remains challenging because of heterogeneous responses to chemotherapy. Incomplete response is associated with a greater risk of metastatic progression. Therefore, treatments that target chemotherapy-resistant TNBC and enhance chemosensitivity would improve outcomes for these high-risk patients.

Management of Pediatric Breast Masses: A Multi-institutional Retrospective Cohort Study.

Background: The objective of our study was to describe the workup, management, and outcomes of pediatric patients with breast masses undergoing operative intervention.

Materials And Methods: A retrospective cohort study was conducted of girls 10-21 y of age who underwent surgery for a breast mass across 11 children's hospitals from 2011 to 2016. Demographic and clinical characteristics were summarized.

Association of Insulin Resistance and Higher Oncotype DX™ Recurrence Score.

Background: Black women with breast cancer have a worse overall survival compared with White women; however, no difference in Oncotype DX™ (ODX) recurrence scores has been observed to explain this health disparity. Black women are also disproportionately affected by insulin resistance. We evaluated whether insulin resistance is associated with a higher ODX recurrence score and whether there is a difference between White and Black women to explain disparate clinical outcomes.

Response in breast vs axilla after neoadjuvant treatment and implications for nonoperative management of invasive breast cancer.

Improved imaging and neoadjuvant chemotherapy (NAT) have led to higher pathologic complete response rates (pCR) in patients with invasive breast cancer. This has questioned the necessity of surgery and axillary lymph node (ALN) dissection in these patients. Prospective clinical trials are implementing extensive core biopsies of the tumor bed of patients with clinical complete response as a means to identify and spare them breast surgery.

Trends in neoadjuvant chemotherapy versus surgery-first in stage I HER2-positive breast cancer patients in the National Cancer DataBase (NCDB).

Background: Neoadjuvant chemotherapy (NAC) is the standard of care for locally advanced HER2 + breast cancer (BC). Optimal sequencing of treatment (NAC vs. surgery first) is less clear cut in stage I (T1N0) HER2 + BC, where information from surgical pathology could impact adjuvant treatment decisions.

Clinical outcomes following implementation of a management bundle for esophageal atresia with distal tracheoesophageal fistula.

Background/purpose: This study evaluated compliance with a multi-institutional quality improvement management protocol for Type-C esophageal atresia with distal tracheoesophageal fistula (EA/TEF).

Methods: Compliance and outcomes before and after implementation of a perioperative protocol bundle for infants undergoing Type-C EA/TEF repair were compared across 11 children's hospitals from 1/2016-1/2019. Bundle components included elimination of prosthetic material between tracheal and esophageal suture lines during repair, not leaving a transanastomotic tube at the conclusion of repair (NO-TUBE), obtaining an esophagram by postoperative-day-5, and discontinuing prophylactic antibiotics 24 h postoperatively.

Adherence to NCCN Guidelines for Genetic Testing in Breast Cancer Patients: Who Are We Missing?

Background: Genetic predisposition accounts for 5-10% of all breast cancers (BC) diagnosed. NCCN guidelines help providers identify appropriate candidates for counseling and testing. Concerns about underutilization of genetic testing have spurred interest in broader peri-diagnostic testing.

Use of neoadjuvant versus adjuvant chemotherapy for hormone receptor-positive breast cancer: a National Cancer Database (NCDB) study.

Introduction: Neoadjuvant chemotherapy (NAC) is a well-established therapeutic option for patients with locally advanced disease often allowing downstaging and facilitation of breast conserving therapy. With evolution of better targeted treatment regimens and awareness of improved outcomes for significant responders, use of NAC has expanded particularly for triple negative and HER2-positive (HER2+) breast cancer. In this study, we explore utility of neoadjuvant chemotherapy for hormone receptor-positive HER2-negative (HR+ HER2-) patients.

Echocardiography Reveals Heart Abnormalities in Pediatric Pectus Carinatum.

Background: Symptoms including chest pain and palpitations are commonly described by pediatric patients with pectus deformity. Cardiac anomalies are thought to be less common in patients with pectus carinatum (PC) than those in patients with pectus excavatum; however, no literature supports this presumption. Echocardiogram (echo) assesses heart structure and function.

Rapid scale-up and production of active-loaded PEGylated liposomes.

Manufacturing of liposomal nanomedicines (e.g. Doxil®/Caelyx®) is a challenging and slow process based on multiple-vessel and batch processing techniques.

PRKCQ inhibition enhances chemosensitivity of triple-negative breast cancer by regulating Bim.

Background: Protein kinase C theta, (PRKCQ/PKCθ) is a serine/threonine kinase that is highly expressed in a subset of triple-negative breast cancers (TNBC) and promotes their growth, anoikis resistance, epithelial-mesenchymal transition (EMT), and invasion. Here, we show that PRKCQ regulates the sensitivity of TNBC cells to apoptosis triggered by standard-of-care chemotherapy by regulating levels of pro-apoptotic Bim.

Methods: To determine the effects of PRKCQ expression on chemotherapy-induced apoptosis, shRNA and cDNA vectors were used to modulate the PRKCQ expression in MCF-10A breast epithelial cells or triple-negative breast cancer cells (MDA-MB231Luc, HCC1806).