Low-Molecular-Weight Cyclin E in Human Cancer: Cellular Consequences and Opportunities for Targeted Therapies.

Cyclin E, a regulatory subunit of cyclin-dependent kinase 2 (CDK2), is central to the initiation of DNA replication at the G/S checkpoint. Tight temporal control of cyclin E is essential to the coordination of cell-cycle processes and the maintenance of genome integrity. Overexpression of cyclin E in human tumors was first observed in the 1990s and led to the identification of oncogenic roles for deregulated cyclin E in experimental models.

Disease-Free and Overall Survival Among Patients With Operable HER2-Positive Breast Cancer Treated With Sequential vs Concurrent Chemotherapy: The ACOSOG Z1041 (Alliance) Randomized Clinical Trial.

Importance: Pathologic complete response rate (pCR), the primary end point of the ACOSOG (American College of Surgeons Oncology Group) Z1041 (Alliance) trial, and disease-free survival (DFS) and overall survival (OS) in women with operable HER2-positive breast cancer are similar between treatment regimens.

Objective: To assess DFS and OS for patients treated with sequential vs concurrent anthracycline plus trastuzumab.

Design, Setting, And Participants: Phase 3 randomized clinical trial conducted at 36 centers in the continental United States and Puerto Rico.

Cyclin E Overexpression Sensitizes Triple-Negative Breast Cancer to Wee1 Kinase Inhibition.

Purpose: Poor prognosis in triple-negative breast cancer (TNBC) is due to an aggressive phenotype and lack of biomarker-driven targeted therapies. Overexpression of cyclin E and phosphorylated-CDK2 are correlated with poor survival in patients with TNBC, and the absence of CDK2 desensitizes cells to inhibition of Wee1 kinase, a key cell-cycle regulator. We hypothesize that cyclin E expression can predict response to therapies, which include the Wee1 kinase inhibitor, AZD1775.

Functional Annotation of ESR1 Gene Fusions in Estrogen Receptor-Positive Breast Cancer.

RNA sequencing (RNA-seq) detects estrogen receptor alpha gene (ESR1) fusion transcripts in estrogen receptor-positive (ER) breast cancer, but their role in disease pathogenesis remains unclear. We examined multiple ESR1 fusions and found that two, both identified in advanced endocrine treatment-resistant disease, encoded stable and functional fusion proteins. In both examples, ESR1-e6>YAP1 and ESR1-e6>PCDH11X, ESR1 exons 1-6 were fused in frame to C-terminal sequences from the partner gene.

Prospective Study of Psychosocial Outcomes of Having Contralateral Prophylactic Mastectomy Among Women With Nonhereditary Breast Cancer.

Purpose The incidence of contralateral prophylactic mastectomy (CPM) has continued to increase. We prospectively examined psychosocial outcomes before and up to 18 months after surgery in women who did or did not have CPM. Methods Women with unilateral, nonhereditary breast cancer completed questionnaires before and 1, 6, 12, and 18 months after surgery.

In utero exposure to tobacco smoke, subsequent cardiometabolic risks, and metabolic syndrome among U.S. adolescents.

Purpose: Maternal smoking during pregnancy increases risk of adverse pregnancy outcomes. However, little is known regarding in utero smoke exposure and offspring cardiometabolic risk. Thus, we examined the association between in utero smoke exposure and cardiometabolic risk factors and the metabolic syndrome (MetS) in adolescents.

Incorporating Biologic Factors into the American Joint Committee on Cancer Breast Cancer Staging System: Review of the Supporting Evidence.

The American Joint Committee on Cancer staging system has evolved in response to improved imaging, refined surgical techniques, enhanced pathologic evaluation, and greater understanding of tumor biology. The 8th edition has introduced clinical and pathologic prognostic stages for breast cancer that incorporate biologic variables (grade, estrogen/progesterone receptor status, HER2 status, multigene panels) with TNM categories that define the anatomic stage. The prognostic staging system facilitates more refined stratification than the anatomic stage with respect to survival and is an important advance that maintains the clinical relevance of the staging system by taking into account tumor biology and current treatment algorithms.

The Feasibility of Breast-Conserving Surgery for Multiple Ipsilateral Breast Cancer: An Initial Report from ACOSOG Z11102 (Alliance) Trial.

Background: Historically, multiple ipsilateral breast cancer (MIBC) has been a contraindication to breast-conserving therapy (BCT). We report the feasibility of BCT in MIBC from the ACOSOG Z11102 trial [Alliance], a single arm noninferiority trial of BCT for women with two or three sites of malignancy in the ipsilateral breast.

Methods: Women who enrolled preoperatively in ACOSOG Z11102 were evaluated for conversion to mastectomy and need for reoperation to obtain negative margins.

American Society of Breast Surgeons' Practice Patterns After Publication of the SSO-ASTRO-ASCO DCIS Consensus Guideline on Margins for Breast-Conserving Surgery With Whole-Breast Irradiation.

Background: The SSO-ASTRO-ASCO consensus guideline on margins for breast-conserving surgery with whole breast irradiation in ductal carcinoma in situ (DCIS) recommended a 2-mm margin. We sought to determine the impact of guideline publication on clinician practice.

Methods: A total of 3081 members of the American Society of Breast Surgeons (ASBrS) received a survey.

Lymphedema symptoms and limb measurement changes in breast cancer survivors treated with neoadjuvant chemotherapy and axillary dissection: results of American College of Surgeons Oncology Group (ACOSOG) Z1071 (Alliance) substudy.

Purpose: Lymphedema is a potential complication of breast cancer treatment. This longitudinal substudy aimed to prospectively assess arm measurements and symptoms following neoadjuvant chemotherapy and axillary dissection in the ACOSOG/Alliance Z1071 trial to characterize the optimal approach to define lymphedema.

Methods: Z1071 enrolled patients with cT0-4, N1-2, M0 disease treated with neoadjuvant chemotherapy.

The interaction between rural/urban status and dual use status among veterans with heart failure.

Introduction: Dual healthcare system use is associated with higher rates of healthcare utilization, but the influence of rurality on this phenomenon is unclear. This study aimed to determine the extent to which rurality in the USA modifies the likelihood for acute healthcare use among veterans with heart failure (HF).

Methods: Using merged Veterans Affairs (VA), Medicare, and state-level administrative data, a retrospective cohort study of 4985 veterans with HF was performed.

Risk factors for locoregional disease recurrence after breast-conserving therapy in patients with breast cancer treated with neoadjuvant chemotherapy: An international collaboration and individual patient meta-analysis.

Background: Several studies have reported a high risk of local disease recurrence (LR) and locoregional disease recurrence (LRR) in patients with breast cancer after neoadjuvant chemotherapy (NCT) and breast-conserving therapy (BCT). The objective of the current study was to identify potential risk factors for LR and LRR after NCT and BCT.

Methods: Individual patient data sets from 9 studies were pooled.

Nongastrointestinal Stromal Tumor Spindle Cell Sarcomas of the Colon or Rectum.

Because of the low incidence of nongastrointestinal stromal tumor (non-GIST) spindle cell sarcomas of the colon or rectum, the clinical behavior and ideal surgical treatment of these tumors and patient outcomes are poorly defined. The purpose of this study was to characterize these tumors and to determine the best surgical approach. We identified 1056 patients with non-GIST spindle cell sarcomas of the colon or rectum (1998-2010) in the National Cancer Database and collected data for each patient that included patient and tumor characteristics, tumor site (colon vs rectum), surgery type, and outcomes.

Salvage Surgery for Recurrent Retroperitoneal Well-Differentiated Liposarcoma: Early Reoperation may not Provide Benefit.

Purpose: Current evidence regarding salvage resection for recurrent retroperitoneal (RP) sarcomas generally lacks detailed histology-specific analyses, but the aggressiveness of these tumors varies widely by histology. We investigated associations between timing and extent of salvage surgery and survival outcomes in patients with recurrent RP well-differentiated liposarcoma (WDLPS).

Methods: The University of Texas MD Anderson Cancer Center Surgical Oncology sarcoma database was reviewed to identify patients with RP WDLPS who underwent surgical resection for first recurrent disease (salvage surgery) in 1995-2015.

Long-term Patient-Reported Outcomes in Older Breast Cancer Survivors: A Population-Based Survey Study.

Purpose: For older women with breast cancer, local therapy options may include lumpectomy plus whole-breast irradiation (Lump + WBI), lumpectomy plus brachytherapy (Lump + Brachy), lumpectomy alone (Lump alone), mastectomy without radiation therapy (Mast alone), and mastectomy plus radiation therapy (Mast + RT). We surveyed a population-based cohort of older breast cancer survivors to assess the association of local therapy with long-term quality-of-life outcomes.

Methods And Materials: We used nationally comprehensive Medicare claims to identify women aged ≥67 years in whom nonmetastatic breast cancer was diagnosed in 2009, who were treated with 1 of the 5 aforementioned treatment options, and who were still alive in 2015.

Comparative Performance of the 7th and 8th Editions of the American Joint Committee on Cancer Staging Systems for Soft Tissue Sarcoma of the Trunk and Extremities.

Background: The 8th edition American Joint Committee on Cancer (AJCC) staging for soft tissue sarcomas of the trunk/extremities divides T stage into four categories and upstages nodal disease to stage IV. We used the National Cancer Database (NCDB) to evaluate the prognostic power of the new system.

Methods: A total of 26,144 patients were identified from the NCDB from 2004 to 2013.

Identification of preoperative factors associated with outcomes following surgical management of intra-abdominal recurrent or metastatic GIST following neoadjuvant tyrosine kinase inhibitor therapy.

Background: The role of surgical resection in the treatment of patients with metastatic/recurrent gastrointestinal stromal tumors (GIST) is unclear. The aim of this study was to identify preoperative factors associated with oncologic outcomes for recurrent/metastatic GIST after tyrosine kinase inhibitor (TKI) therapy.

Methods: We identified 107 patients with metastatic or recurrent GIST treated with TKIs and surgical resection (2002-2012).

Plasma Connective Tissue Growth Factor (CTGF/CCN2) Levels Predict Myocardial Infarction in the Veterans Affairs Diabetes Trial (VADT) Cohort.

Objective: Connective tissue growth factor (CTGF), also known as CCN2, is a potent chemotactic and extracellular matrix-inducing matricellular protein that has been implicated in progression of inflammatory and fibroproliferative disorders. An emerging role of CTGF/CCN2 is that of a prosclerotic factor implicated in the development of cardiac disease. Our objective was to determine the role of CTGF/CCN2 as a predictor of cardiovascular events in type 2 diabetes in the Veterans Affairs Diabetes Trial (VADT) cohort.

Axillary Ultrasound Identifies Residual Nodal Disease After Chemotherapy: Results From the American College of Surgeons Oncology Group Z1071 Trial (Alliance).

Objective: The purpose of this study is to determine lymph node features on axillary ultrasound (US) images obtained after neoadjuvant chemotherapy that are associated with residual nodal disease in patients with initial biopsy-proven node-positive breast cancer.

Subjects And Methods: All patients had axillary US performed after neoadjuvant chemotherapy. Axillary US images were centrally reviewed for lymph node size, cortical thickness, and cortical morphologic findings (type I indicated no visible cortex; type II, a hypoechoic cortex ≤ 3 mm; type III, a hypoechoic cortex > 3 mm; type IV, a generalized lobulated hypoechoic cortex; type V, focal hypoechoic cortical lobulation; and type VI, a totally hypoechoic node with no hilum).

ShinyGPA: An interactive visualization toolkit for investigating pleiotropic architecture using GWAS datasets.

In spite of accumulating evidence suggesting that different complex traits share a common risk basis, namely pleiotropy, effective investigation of pleiotropic architecture still remains challenging. In order to address this challenge, we developed ShinyGPA, an interactive and dynamic visualization toolkit to investigate pleiotropic structure. ShinyGPA requires only the summary statistics from genome-wide association studies (GWAS), which reduces the burden on researchers using this tool.

Analysis of the immune infiltrate in undifferentiated pleomorphic sarcoma of the extremity and trunk in response to radiotherapy: Rationale for combination neoadjuvant immune checkpoint inhibition and radiotherapy.

: Undifferentiated pleomorphic sarcoma of the extremity and trunk (ET-UPS) presents a unique therapeutic challenge. Although immunotherapy has recently been employed in advanced soft tissue sarcoma, there is limited data characterizing the immune infiltrate in ET-UPS. Radiotherapy (RT) has been shown in other tumor types to promote tumor antigen release and enhance tumor-specific targeting by the adaptive immune system.

Concomitant organ resection does not improve outcomes in primary retroperitoneal well-differentiated liposarcoma: A retrospective cohort study at a major sarcoma center.

Background: We investigated whether concomitant organ removal as part of the primary resection of RP WDLPS confers an outcome advantage in patients treated at a major sarcoma center.

Methods: The departmental sarcoma database was reviewed to identify patients with RP WDLPS who underwent initial surgical resection for primary disease at MD Anderson Cancer Center during the study period 1995-2011. We retrospectively reviewed medical records and examined associations between clinicopathologic variables and overall survival (OS) as well as disease-free survival (DFS).