Persistent organic pollutants and mammographic density

Institution: University of Southern California
Investigator(s): Eunjung  Lee ,  -
Award Cycle: 2014 (Cycle 20) Grant #: 20IB-0114 Award: $248,244
Award Type: IDEA
Research Priorities
Etiology and Prevention>Etiology: the role of environment and lifestyle



Initial Award Abstract (2014)

Non-technical overview of the research topic and relevance to breast cancer: Persistent Organic Pollutants (POPs) are a large, diverse group of synthetic compounds that are highly toxic, accumulate in the food chain and human body, and persist in the environment for decades. Extensive laboratory data have suggested a cancer-causing and estrogenic potential of POPs. Estrogens are sex-steroid hormones that are known to elevate breast cancer risk. Thus, existing laboratory data support that POPs may cause breast cancer. However, human data have been inconsistent and largely limited to earlier classes of POPs. In particular, newer classes of POPs that have been extensively used in a variety of commercial products as waterproof and non-stick coatings or as flame retardants in plastics and furniture, have rarely been studied in relation to breast cancer risk. Given that POPs are widely used and we cannot control our exposure to these chemicals as individuals, it is essential to investigate human breast cancer impact of these chemicals.

Women’s exposure to POPs could occur from diverse sources in complicated ways; thus, it is best to assess one’s POPs exposure levels by laboratory techniques using biological samples (e.g. blood). This creates two critical obstacles that have prevented the scientific community from investigating POPs-breast cancer link: (1) the extremely high cost of comprehensive laboratory measurement of POPs, and (2) limited availability of appropriate (i.e. obtained prior to breast cancer diagnosis) biological samples of breast cancer patients. In this IDEA application, we propose to investigate the association between blood levels of POPs and breast cancer risk by using an established biomarker for breast cancer risk - mammographic density (MD).

On standard mammograms the dark area represents fat tissue, while light area represents breast tissue. The relative amount of the dense area on the mammogram, referred to as mammographic density (MD), is one of the strongest known predictors of breast cancer. MD can be determined on regular screening mammograms. By using this breast cancer biomarker, we can investigate the POPs-breast cancer link among women without breast cancer.

Our proposal avoids the cost-related obstacle by capitalizing on an ongoing CBCRP-funded study (#16ZB-8501; PI: Peggy Reynolds, co-investigator of this IDEA application), where blood POPs levels are comprehensively being measured and will be compared between breast cancer patients and control women sampled from the California Teachers Study (CTS) cohort. Second, our study design of using a breast cancer biomarker and conducting the study only among non-cases allows us to avoid the second obstacle stemming from the use of blood samples of breast cancer patients (i.e. that may be affected by being obtained after breast cancer diagnosis and treatment).

The question(s) or central hypotheses of the research: We hypothesize that serum POPs levels are positively associated with higher MD, which is a known predictor of increased breast cancer risk.

The general methodology: The study participants will be 160 postmenopausal women identified from the pool of ~1,100 participants without breast cancer in the “CTS POPs study” (#16ZB-8501), whose serum POPs levels are comprehensively being measured. From the participants in this proposed study, we will collect mammograms along with information on potential confounders. A highly experienced researcher will assess MD of the 160 women using a well validated computer-assisted tool. The association between POPs levels and MD will be investigated using linear regression analyses (i.e. a type of statistical methods) taking into account potential confounders. We will analyze the data using various advanced statistical techniques, evaluating each compound individually and as combinations considering a priori groupings by chemical classes, biological properties, and correlations (i.e. inter-relationships) between each compound.

Innovative elements of the project: To our knowledge, we are the first to investigate the association between a comprehensive list of POPs and breast cancer risk among women without breast cancer using an established biomarker of breast cancer risk. This study design is innovative in that this approach allows us to avoid the limitations of cost and timing of blood collection as discussed above. In particular, we are investigating a comprehensive list of POPs, not only the old but also the new POPs in relation to breast cancer risk. Considering that these newer POPs are widely detected in the US population, it is surprising that their breast carcinogenic potentials have rarely been investigated in human populations. Our study is innovative in that we are investigating this rarely-addressed but important area of breast cancer research.




Progress Report 1 (2015)

Persistent Organic Pollutants (POPs) are a large, diverse group of synthetic compounds that are highly toxic, accumulate in the food chain and human body, and persist in the environment for decades. Existing laboratory data support that POPs may cause breast cancer. However, human data have been inconsistent and largely limited to earlier classes of POPs. We hypothesize that serum POPs levels are positively associated with higher mammographic density (MD), which is the relative amount of the dense area on the mammogram and a known predictor of increased breast cancer risk.

In the first year of the current grant, we planned to develop study materials such as consent documents and survey forms, obtain IRB approval, initiate recruitment of the study participants and collect mammograms and survey data. As planned, we have developed study materials, obtained IRB approval and identified potentially eligible participants and started recruitment and data collection. Our goal is to recruit 160 women. During the first year of this study, we have sent out study invitation letters to 74 women. Of these, 11 women were ineligible or refused to participate; 41 women participated and completed the survey; and an additional 10 women agreed to participate and are in the process of completing the study survey forms. We are re-contacting the non-respondents from this first set of recruitment efforts as well as sending invitation to another 100 potentially eligible participants. For women who returned their survey forms, we entered and cleaned survey data, contacted mammography facilities as indicated on the survey form, and collected mammograms. Although we experienced delays in starting the project, our recruitment progress and study achievements since are at the anticipated pace. We have not encountered any major barrier while conducting the study activities.

Plans for the next project year are to continue participant recruitment and data collection, evaluate mammographic density, perform statistical analyses, and prepare a manuscript.




Progress Report 2 (2015)

During the past 18 months of the grant period, we have developed study materials, obtained IRB approval, identified potentially eligible participants and started recruitment and data collection. Our goal is to recruit 160 women. Currently, we have invited 211 women. Of those 211 women, 31 women were ineligible or refused to participate; 106 women participated and completed the survey. We are re-contacting the non-respondents and in the process of sending invitations to another 30 potentially eligible participants. We expect that we will be able to recruit 160 women from the recruitment efforts.

For women who returned their survey forms, we entered and cleaned data, contacted mammography facilities as indicated on the survey form, and collected mammograms. Although we experienced delays in starting the project, our recruitment progress and study achievements are at the anticipated pace. We have not encountered any major barriers while conducting the study activities.

We will continue participant and data collection, evaluate mammographic density, perform statistical analyses, and prepare a manuscript. To achieve these aims, we have submitted a request for a no-cost time extension.