Epidemiology and Risk Factors for Breast Cancer: 21st Century Advances, Gaps to Address through Interdisciplinary Science.

Research methods to study risk factors and prevention of breast cancer have evolved rapidly. We focus on advances from epidemiologic studies reported over the past two decades addressing scientific discoveries, as well as their clinical and public health translation for breast cancer risk reduction. In addition to reviewing methodology advances such as widespread assessment of mammographic density and Mendelian randomization, we summarize the recent evidence with a focus on the timing of exposure and windows of susceptibility.

Phase I trial of ATM inhibitor M3541 in combination with palliative radiotherapy in patients with solid tumors.

Background: Ataxia telangiectasia mutated (ATM) kinase orchestrates DNA double strand break (DSB) repair; ATM inhibitors may therefore enhance the therapeutic effect of DSB-inducing treatments such as radiotherapy (RT). M3541 is an orally administered selective inhibitor of ATM.

Methods: This phase I dose-escalation study evaluated the maximum-tolerated dose (MTD), recommended phase II dose(s) (RP2D), safety, pharmacokinetics (PK) and antitumor activity of M3541 in combination with fractionated palliative RT in patients with solid tumors.

Culturing Primary Human Mesothelial Cells.

Mesothelial cells line the serosal cavities and associated organs. In order to metastasize to distant organs, ovarian tumor cells must first attach and then clear the mesothelial cells. Therefore, human primary mesothelial cells (HPMCs) are necessary to effectively study ovarian cancer metastases.

Adolescent alcohol, nuts, and fiber: combined effects on benign breast disease risk in young women.

Adolescent drinking is associated with higher risks of proliferative benign breast disease (BBD) and invasive breast cancer (BC). Furthermore, adolescent nut and fiber consumptions are associated with lower risks of benign lesions and premenopausal BC. We hypothesize that diet (nuts, fiber) may mitigate the elevated BBD risk associated with alcohol.

Automated Quantitative Measures of Terminal Duct Lobular Unit Involution and Breast Cancer Risk.

Background: Manual qualitative and quantitative measures of terminal duct lobular unit (TDLU) involution were previously reported to be inversely associated with breast cancer risk. We developed and applied a deep learning method to yield quantitative measures of TDLU involution in normal breast tissue. We assessed the associations of these automated measures with breast cancer risk factors and risk.

Deep learning assessment of breast terminal duct lobular unit involution: Towards automated prediction of breast cancer risk.

Terminal duct lobular unit (TDLU) involution is the regression of milk-producing structures in the breast. Women with less TDLU involution are more likely to develop breast cancer. A major bottleneck in studying TDLU involution in large cohort studies is the need for labor-intensive manual assessment of TDLUs.

Dietary intake from birth through adolescence in relation to risk of benign breast disease in young women.

Purpose: Nutritional factors during different periods in life impact breast cancer risk. Because benign breast disease (BBD) is a well-established risk factor for breast cancer, we investigated childhood nutrition from birth through age 14 year and subsequent BBD.

Methods: A prospective cohort study of 9031 females, 9-15 year at baseline, completed questionnaires (including heights, weights) annually from 1996 to 2001, in 2003, 2005, 2007, 2010, 2013 and 2014.

Endometrial Tumor Immune Response: Predictive Biomarker of Response to Immunotherapy.

The tumor-specific immune response in endometrial cancer is variable within molecular subtypes. Thus, the tumor immune response offers a novel biomarker, separate from molecular subtypes, to predict which patients might respond to immunotherapy..

Eight ways to stay healthy after cancer: an evidence-based message.

Purpose: Since 1999, in conjunction with the internationally known and award-winning Your Disease Risk ( yourdiseaserisk.org ) risk assessment tool, the "Eight Ways to Stay Healthy and Prevent Cancer" message campaign has provided an evidence-based, but user-friendly, approach to cancer prevention. The scientific evidence behind the campaign is robust and while not a complete list, provides a great deal of benefit in the reduction of cancer risk.

Design and conduct of intervention-based research among cancer survivors.

Intervention trials in cancer survivors play an important and growing role in complementing the wealth of knowledge obtained from observational studies about how lifestyle can improve clinical, physiologic, and psychological outcomes. As the number of intervention trials grows, attention to study design and reporting is essential to establishing a high-quality data pool from which to make evidence-based recommendations and guidelines. We highlight several key issues important to the design and interpretation of intervention trials in cancer survivors.

A phase II study of carboplatin, etoposide, and exisulind in patients with extensive small cell lung cancer: CALGB 30104.

Purpose: To assess the efficacy and toxicity of carboplatin, etoposide, and exisulind as initial therapy for extensive stage small cell lung cancer.

Patients And Methods: The Cancer and Leukemia Group B conducted a phase II study of carboplatin (area under the curve 6) day 1 and etoposide 80 mg/m(2) days 1-3 administered intravenously every 21 days with exisulind 250 mg orally twice daily in 44 evaluable patients with previously untreated extensive stage small cell lung cancer. The hypothesis was the addition of a novel cytostatic agent to standard therapy may increase survival time.

A unified sample preparation protocol for proteomic and genomic profiling of cervical swabs to identify biomarkers for cervical cancer screening.

Cervical cancer screening is ideally suited for the development of biomarkers due to the ease of tissue acquisition and the well-established histological transitions. Furthermore, cell and biologic fluid obtained from cervix samples undergo specific molecular changes that can be profiled. However, the ideal manner and techniques for preparing cervical samples remains to be determined.

Treatment of patients excluded from Eastern Cooperative Oncology Group 4599 and AVAiL studies: focus on brain metastasis and squamous histology.

Bevacizumab is the first molecularly targeted agent associated with improved outcomes in combination with chemotherapy in previously untreated patients with non-small-cell lung cancer (NSCLC). The addition of bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), to carboplatin and paclitaxel resulted in a significant improvement in overall survival compared with chemotherapy alone; however, bevacizumab is associated with increased risk of severe complications, including hemoptysis, neutropenic fever, and gastrointestinal perforation. Based on the initial observations that patients with squamous cell carcinoma treated with bevacizumab are at high risk for severe and fatal hemoptysis, these patients were not included in subsequent phase III clinical trials involving this agent.

Retroperitoneal lymph node resection in patients with cervical cancer.

Objective: To determine predictive factors precluding complete resection of metastatic lymph nodes identified by pre-operative imaging in patients with cervical cancer.

Methods: Retrospective clinical review of patients with cervical cancer with suspected metastases to pelvic and/or periaortic lymph nodes who underwent lymph node dissection by laparotomy at The University of Texas M.D.

Preoperative lymph node staging of early-stage cervical carcinoma by [18F]-fluoro-2-deoxy-D-glucose-positron emission tomography.

Background: Increasing evidence has documented the value of positron emission tomography (PET) in oncology, but only limited data are available comparing PET findings with the pathologic status of regional lymph nodes in patients with cervical carcinoma. The objective of this study was to determine the sensitivity and specificity of PET in detecting lymph node metastasis in women with early-stage cervical carcinoma.

Methods: The authors performed a retrospective review of all patients with Stage IA-IIA cervical carcinoma who underwent PET before surgery from 1999 to 2004.