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Screening for Chemical Contributions to Breast Cancer Risk: A Case Study for Chemical Safety Evaluation.

ABSTRACT: Current approaches to chemical screening, prioritization, and assessment are being reenvisioned, driven by innovations in chemical safety testing, new chemical regulations, and demand for information on human and environmental impacts of chemicals. To conceptualize these changes through the lens of a prevalent disease, the Breast Cancer and Chemicals Policy project convened an interdisciplinary expert panel to investigate methods for identifying chemicals that may increase breast cancer risk.Based on a review of current evidence, the panel identified key biological processes whose perturbation may alter breast cancer risk. We identified corresponding assays to develop the Hazard Identification Approach for Breast Carcinogens (HIA-BC), a method for detecting chemicals that may raise breast cancer risk. Finally, we conducted a literature-based pilot test of the HIA-BC.The HIA-BC identifies assays capable of detecting alterations to biological processes relevant to breast cancer, including cellular and molecular events, tissue changes, and factors that alter susceptibility. In the pilot test of the HIA-BC, chemicals associated with breast cancer all demonstrated genotoxic or endocrine activity, but not necessarily both. Significant data gaps persist.This approach could inform the development of toxicity testing that targets mechanisms relevant to breast cancer, providing a basis for identifying safer chemicals. The study identified important end points not currently evaluated by federal testing programs, including altered mammary gland development, Her2 activation, progesterone receptor activity, prolactin effects, and aspects of estrogen receptor ? activity. This approach could be extended to identify the biological processes and screening methods relevant for other common diseases.

SUBMITTER: Schwarzman MR

PROVIDER: S-EPMC4671249 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Screening for Chemical Contributions to Breast Cancer Risk: A Case Study for Chemical Safety Evaluation.

Schwarzman Megan R MR Ackerman Janet M JM Dairkee Shanaz H SH Fenton Suzanne E SE Johnson Dale D Navarro Kathleen M KM Osborne Gwendolyn G Rudel Ruthann A RA Solomon Gina M GM Zeise Lauren L Janssen Sarah S

Environmental health perspectives 20150602 12

<h4>Background</h4>Current approaches to chemical screening, prioritization, and assessment are being reenvisioned, driven by innovations in chemical safety testing, new chemical regulations, and demand for information on human and environmental impacts of chemicals. To conceptualize these changes through the lens of a prevalent disease, the Breast Cancer and Chemicals Policy project convened an interdisciplinary expert panel to investigate methods for identifying chemicals that may increase bre ...[more]

PMID: 26032647

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Project description:To evaluate the implementations of Cancer Screening Program in Urban Hebei and to model the cost-effectiveness of a risk-based breast Cancer Screening Program. Women aged 40–74 years were invited to participate the Cancer Screening Program in Urban Hebei form 2016 to 2020 by completing questionnaires to collect information about breast cancer exposure. Clinical screening including ultrasound and mammography examination were performed. We developed a Markov model to estimate the lifetime costs and benefits, in terms of quality-adjusted life years (QALY), of a high-risk breast Cancer Screening Program. Nine screening strategies and no screening were included in the study. The age-specific incidence, transition probability data and lifetime treatment costs were derived and adopted from other researches. Average cost-effectiveness ratios (ACERs) were estimated as the ratios of the additional costs of the screening strategies to the QLYG compared to no screening. Incremental cost-effectiveness ratios (ICERs) were calculated based on the comparison of a lower cost strategies to the next more expensive and effective strategies after excluding dominated strategies and extendedly dominated strategies. ICERs were used to compare with a willingness-to-pay (WTP) threshold. Sensitivity analysis was explored the influence factors. A total of 84,029 women completed a risk assessment questionnaire, from which 20,655 high-risk breast cancer females were evaluated, with a high-risk rate of 24.58%. There were 13,392 high-risk females completed the screening program, with participation rate was 64.84%. Undergoing ultrasound, mammography and combined screening, the suspicious positive detection rates were 15.00%, 9.20% and 19.30%, and the positive detection rates were 2.11%, 2.76% and 3.83%, respectively. According to the results by Markov model, at the end of 45 cycle, the early diagnosis rates were 55.53%, 60.68% and 62.47% underwent the annual screening by ultrasound, mammography and combined, the proportion of advanced cancer were 17.20%, 15.85% and 15.36%, respectively. Different screening method and interval yield varied. In the exploration of various scenarios, annual ultrasound screening is the most cost-effective strategy with the ICER of ¥116,176.15/QALY. Sensitivity analyses demonstrated that the results are robust. Although it was not cost effective, combined ultrasound and mammography screening was an effective strategy for higher positive detection rate of breast cancer. High-risk population-based breast cancer screening by ultrasound annually was the most cost-effective strategy in Urban Hebei Province.

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Project description:The magnitude of the tradeoff between recall rate (RR) and cancer detection rate (CDR) in breast-cancer screening is not clear, and it is expected to depend on target population and screening program characteristics. Multi-reader multi-case research studies, which may be used to estimate this tradeoff, rely on enriched datasets with artificially high prevalence rates, which may bias the results. Furthermore, readers participating in research studies are subject to "laboratory" effects, which can alter their performance relative to actual practice. The Recall and detection Of breast Cancer in Screening (ROCS) trial uses a novel data acquisition system that minimizes these limitations while obtaining an estimate of the RR-CDR curve during actual practice in the Dutch National Breast Cancer Screening Program. ROCS involves collection of at least 40,000 probability-of-malignancy ratings from at least 20 radiologists during interpretation of approximately 2,000 digital mammography screening cases each. With the use of custom-built software on a tablet, and a webcam, this data was obtained in the usual reading environment with minimal workflow disruption and without electronic access to the review workstation software. Comparison of the results to short- and medium-term follow-up allows for estimation of the RR-CDR and receiver operating characteristics curves, respectively. The anticipated result of the study is that performance-based evidence from practice will be available to determine the optimal operating point for breast-cancer screening. In addition, this data will be useful as a benchmark when evaluating the impact of potential new screening technologies, such as digital breast tomosynthesis or artificial intelligence. KEY POINTS: • The ROCS trial aims to estimate the recall rate-cancer detection rate curve during actual screening practice in the Dutch National Breast Cancer Screening Program. • The study design is aimed at avoiding the influence of the "laboratory effect" in usual observer performance studies. • The use of a tablet and a webcam allows for the acquisition of probability of malignancy ratings without access to the review workstation software.

Dataset Information

Screening for Chemical Contributions to Breast Cancer Risk: A Case Study for Chemical Safety Evaluation.

Publications

Screening for Chemical Contributions to Breast Cancer Risk: A Case Study for Chemical Safety Evaluation.

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