Updated Standardized Definitions for Efficacy End Points (STEEP) in Adjuvant Breast Cancer Clinical Trials: STEEP Version 2.0.

Purpose: The Standardized Definitions for Efficacy End Points (STEEP) criteria, established in 2007, provide standardized definitions of adjuvant breast cancer clinical trial end points. Given the evolution of breast cancer clinical trials and improvements in outcomes, a panel of experts reviewed the STEEP criteria to determine whether modifications are needed.

Methods: We conducted systematic searches of ClinicalTrials.

Deep learning analysis of breast MRIs for prediction of occult invasive disease in ductal carcinoma in situ.

Purpose: To determine whether deep learning-based algorithms applied to breast MR images can aid in the prediction of occult invasive disease following the diagnosis of ductal carcinoma in situ (DCIS) by core needle biopsy.

Materials And Methods: Our study is retrospective. The data was collected from 2000 to 2014.

Ductal carcinoma in situ: to treat or not to treat, that is the question.

Ductal carcinoma in situ (DCIS) now represents 20-25% of all 'breast cancers' consequent upon detection by population-based breast cancer screening programmes. Currently, all DCIS lesions are treated, and treatment comprises either mastectomy or breast-conserving surgery supplemented with radiotherapy. However, most DCIS lesions remain indolent.

Surgical Upstaging Rates for Vacuum Assisted Biopsy Proven DCIS: Implications for Active Surveillance Trials.

Purpose: This study was designed to determine invasive cancer upstaging rates at surgical excision following vacuum-assisted biopsy of ductal carcinoma in situ (DCIS) among women meeting eligibility for active surveillance trials.

Methods: Patients with vacuum-assisted, biopsy-proven DCIS at a single center from 2008 to 2015 were retrospectively reviewed. Imaging and pathology reports were interrogated for the imaging appearance, tumor grade, hormone receptor status, and presence of comedonecrosis.

DNA defects, epigenetics, and gene expression in cancer-adjacent breast: a study from The Cancer Genome Atlas.

Recurrence rates after breast-conserving therapy may depend on genomic characteristics of cancer-adjacent, benign-appearing tissue. Studies have not evaluated recurrence in association with multiple genomic characteristics of cancer-adjacent breast tissue. To estimate the prevalence of DNA defects and RNA expression subtypes in cancer-adjacent, benign-appearing breast tissue at least 2 cm from the tumor margin, cancer-adjacent, pathologically well-characterized, benign-appearing breast tissue specimens from The Cancer Genome Atlas project were analyzed for DNA sequence, copy-number variation, DNA methylation, messenger RNA (mRNA) sequence, and mRNA/microRNA expression.

Tissue mechanics modulate microRNA-dependent PTEN expression to regulate malignant progression.

Tissue mechanics regulate development and homeostasis and are consistently modified in tumor progression. Nevertheless, the fundamental molecular mechanisms through which altered mechanics regulate tissue behavior and the clinical relevance of these changes remain unclear. We demonstrate that increased matrix stiffness modulates microRNA expression to drive tumor progression through integrin activation of β-catenin and MYC.

Survival after lumpectomy and mastectomy for early stage invasive breast cancer: the effect of age and hormone receptor status.

Background: Randomized clinical trials (RCT) have demonstrated equivalent survival for breast-conserving therapy with radiation (BCT) and mastectomy for early-stage breast cancer. A large, population-based series of women who underwent BCT or mastectomy was studied to observe whether outcomes of RCT were achieved in the general population, and whether survival differed by surgery type when stratified by age and hormone receptor (HR) status.

Methods: Information was obtained regarding all women diagnosed in the state of California with stage I or II breast cancer between 1990 and 2004, who were treated with either BCT or mastectomy and followed for vital status through December 2009.

Clinical efficacy of taxane-trastuzumab combination regimens for HER-2-positive metastatic breast cancer.

The taxanes docetaxel (Taxotere; Sanofi-Aventis U.S. LLC, Bridgewater, NJ) and paclitaxel (Taxol; Bristol-Myers Squibb, Princeton, NJ) are highly active agents in metastatic breast cancer and may represent a safer alternative to anthracycline-based regimens when combined with the human epidermal growth factor receptor (HER)-2-targeted agent trastuzumab (Herceptin(R); Genentech Inc.

Identification and functional characterization of the human glutathione S-transferase P1 gene as a novel transcriptional target of the p53 tumor suppressor gene.

The glutathione S-transferase P1 (GSTP1) is involved in multiple cellular functions, including phase II metabolism, stress response, signaling, and apoptosis. The mechanisms underlying the significantly high GSTP1 expression in many human tumors are, however, currently not well understood. We report here that the GSTP1 gene is a heretofore unrecognized downstream transcriptional target of the tumor suppressor p53.

Circulating D-dimer levels are better predictors of overall survival and disease progression than carcinoembryonic antigen levels in patients with metastatic colorectal carcinoma.

Background: Fibrin formation is required for tumor angiogenesis, metastasis, and invasion. D-dimer, a fibrin degradation product, is produced when crosslinked fibrin is degraded by plasmin. The current study prospectively examined D-dimer levels in patients with metastatic colorectal carcinoma treated in a Phase II randomized trial comparing bevacizumab (Avastin, Genentech, South San Francisco, CA) plus 5-fluorouracil/leucovorin (5-FU/LV) with 5-FU/LV alone.

HER-2 gene amplification correlates with higher levels of angiogenesis and lower levels of hypoxia in primary breast tumors.

Purpose: This study investigated the connection among HER-2 gene amplification, HER-2 protein expression, and markers of tumor angiogenesis and oxygenation in patients with operable, invasive breast tumors.

Experimental Design: From 1988 to 1995, 425 patients with metastatic breast cancer were enrolled in a study of high-dose chemotherapy with autologous transplant. Primary tumor blocks were obtained and evaluated using immunohistochemistry (IHC) staining of vessels with von Willebrand factor antibody.

Letrozole inhibits tumor proliferation more effectively than tamoxifen independent of HER1/2 expression status.

Background: The biological basis for the superior efficacy of neoadjuvant letrozole versus tamoxifen for postmenopausal women with estrogen receptor (ER)-positive locally advanced breast cancer was investigated by analyzing tumor proliferation and expression of estrogen-regulated genes before and after the initiation of therapy.

Methods: Tumor samples were obtained at baseline and at the end of treatment from 185 patients participating in a double blind randomized Phase III study of neoadjuvant endocrine therapy. These paired specimens were simultaneously analyzed for Ki67, ER, progesterone receptor (PgR), trefoil factor 1 (PS2), HER1 (epidermal growth factor receptor), and HER2 (ErbB2 or neu) by semiquantitative immunohistochemistry.

Human recombinant erythropoietin significantly improves tumor oxygenation independent of its effects on hemoglobin.

Tumor oxygenation is known to be an important predictive/prognostic marker in a variety of tumors, including cervix, head/neck, sarcoma, non-small cell of the lung, and breast. Tumor oxygenation is influenced by many interactions, including oxygen delivery (angiogenesis, permeability, and HgB) and consumption (metabolic and growth rates). This study randomized 30 nonanemic, female Fischer 344 rats into three treatment arms to examine the effects of recombinant human erythropoietin (EPO) on R3230 rodent mammary carcinoma oxygenation.

Letrozole is more effective neoadjuvant endocrine therapy than tamoxifen for ErbB-1- and/or ErbB-2-positive, estrogen receptor-positive primary breast cancer: evidence from a phase III randomized trial.

Purpose: Expression of ErbB-1 and ErbB-2 (epidermal growth factor receptor and HER2/neu) in breast cancer may cause tamoxifen resistance, but not all studies concur. Additionally, the relationship between ErbB-1 and ErbB-2 expression and response to selective aromatase inhibitors is unknown. A neoadjuvant study for primary breast cancer that randomized treatment between letrozole and tamoxifen provided a context within which these issues could be addressed prospectively.

Contemporary chemotherapeutic approaches for the treatment of hormone-refractory prostate carcinoma.

The medical management of hormone-refractory prostate cancer remains difficult and largely palliative. The development of effective antineoplastic agents has been frustrated by difficulty in the establishment of satisfactory objective response criteria for clinical trials. Nevertheless, recent trials indicate that mitoxantrone and spindle toxins such as docetaxel do show activity.

Plasma D-dimer levels in operable breast cancer patients correlate with clinical stage and axillary lymph node status.

Purpose: To investigate the relationship between preoperative plasma D-dimer levels and extent of tumor involvement in operable breast cancer patients.

Patients And Methods: A total of 140 preoperative plasma specimens were obtained from women scheduled to undergo diagnostic breast biopsies. Ninety-five patients in the initial group went on to undergo axillary lymph node dissection.

The evolution of therapy for patients with stage IIIA (N2) lung cancer.

This is a demonstrable case report and discussion of recent trends in neoadjuvant therapy for patients with locally advanced stage IIIA (N2) non-small cell lung cancer.