Impact of Reducing Chemical Exposure to the Human Breast

Institution: California Pacific Medical Center Research Institute
Investigator(s): Shanaz Dairkee, Ph.D. - Polly Marshall, JD -
Award Cycle: 2015 (Cycle 21) Grant #: 21AB-1401 Award: $218,572
Award Type: CRC Pilot Award
Research Priorities
Etiology and Prevention>Prevention and Risk Reduction: ending the danger of breast cancer

This is a collaboration with: 21AB-1400 -

Initial Award Abstract (2015)

Introduction: Manufactured chemicals, such as phthalates and parabens, found in many consumer products are mimics of the natural hormone estrogen. Exposures to these "xenoestrogen" (from the Latin for "foreign" estrogen), or "XE";, have been linked to mammary cancer in rodents and shown to cause  pre-cancerous changes in normal human breast cell cultures grown in the laboratory. Building on recent studies that show that the presence of XEs in blood or urine decreases when study participants decrease their exposure to XEs through changes in diet or use of personal care products, this study seeks to measure the impact of decreased XE exposure from personal care products (PCPs) on healthy human breast cells while still in the human body. The study will use a novel methodology previously developed by research team members to compare breast cells donated by volunteers through fine needle aspiration (FNA) before and after a 28-day healthy intervention requiring use of XE-free personal care products. Studying the role of XEs in cellular changes that precede the genesis of breast cancer could provide key insights into the biological processes of cancer development, and thereby play an important role in breast cancer prevention.

Question(s) or hypotheses: We hypothesize that a healthy intervention that decreases exposure through use of XE-free PCPs will reduce cellular changes in breast tissue that are associated with the development of breast cancer. Specifically, the pilot study aims (1) to discover effective strategies to recruit volunteer study participants willing to donate breast cells through FNA and to maximize their adherence to the 28-day reduced XE intervention requirements, and (2) to determine whether effects of decreased XE exposure are detectable at the cellular level of study participants’ donated breast tissue.

General methodology: For this pilot study, we propose to recruit a total of 16 women, 18-40 years of age, who ordinarily use PCPs containing phthalates and/or parabens. The study participants will contribute urine and blood samples and donate breast cells through FNA performed by a highly experienced breast surgeon. Study participants will be provided with a kit of approved phthalate and paraben-free personal care products to be used in order to decrease XE exposure. After 28 days on the XE-free PCP intervention, FNA, urine and blood samples will be collected again from the participants. Urine samples will be analyzed for  levels  of phthalate and paraben breakdown products, blood samples will be analyzed for base levels of natural hormones, and breast tissue samples will be cultured in the laboratory  and  analyzed  for  specific  cellular features associated with the initiation of breast cancer. Study data will be analyzed to determine if the 28-day use of XE-free products reduces XE exposure as shown by XE levels in urine, and whether it impacts cancer- related features within donor breast cells. Participants will be interviewed to obtain insight into effective recruitment, retention, and compliance for future study design.

Innovative elements: Breast cancer survivor community members will actively recruit and support volunteers willing to donate breast cells and participate in the XE-free PCP intervention.  Normal human breast cells obtained by FNA from healthy donors and cultured in the laboratory will be analyzed for  the  impact  of decreased XE exposure on cellular features associated with breast carcinogenesis. This unique combination of in vivo/in vitro analysis of changes in normal human breast cells will build upon previous work with cancerous human breast cell lines and animal models, and has great potential for use in studies of other environmental chemical exposures.

Community involvement: The impetus for this study was provided by a group of breast cancer survivors seeking to support research into the effects of exposures to carcinogenic chemicals  found  in  consumer products on the genesis of breast cancer. This group of women has sought innovative and experienced cancer researchers to address their research question, and will recruit and support study participants, solicit feedback from the community of interest, assist in data analysis, and translate and publicize results. The community of interest for this study is people who seek to prevent breast cancer in themselves, their families, and generations to come.

Future Plans: The pilot study will provide data regarding the feasibility of studying cellular changes resulting from lessening the XE exposure of healthy young women, as well as insight into effective means of recruitment of healthy breast cell donors and compliance with the "XE-free PCP" intervention. This information will  be invaluable for the design and implementation of a full study with additional populations, to validate the impact of decreased XE exposure on breast cancer prevention.

Progress Report 1 (2016)

This research represents a collaborative effort with breast cancer survivor community members for recruitment and support of volunteers participating in the use of xenoestrogen (XE)-free personal care products (PCPs). Uniquely, healthy breast cells collected from consented premenopausal study subjects are employed towards analyzing the impact of reduced in vivo XE exposure on cellular features associated with breast carcinogenesis in lab-based assays on live cells. During the initial funding period, we have successfully recruited six volunteers into the study, and initiated and/or completed collection of baseline blood samples and serial pre and post-intervention urine and breast FNA samples. Depending on the yield of proliferation-competent cell populations, breast FNAs are currently in various stages of live cell expansion and molecular and functional testing to determine the presence of detectable biological shifts resulting from the elimination of XE exposure through PCPs.

To date, we have consistently demonstrated feasibility of our proposed specific aims, leading to the following major accomplishments:

* Dissemination of study goals in well-attended public forums emphasizing the need for improved approaches to demonstrate the human carcinogenic potential of chemicals common in consumer goods, such as PCPs.

* Screening and recruitment of volunteers for participation in the XEL intervention, and serial sampling of healthy breast tissue by minimal FNA.

* In vitro expansion of live cells isolated from pre and post XEL-intervention healthy breast tissue FNA.

* Multiplexed analysis of estrogen receptor proteins, and concurrent analysis of functional endpoints, such as programmed cell death, and cell cycle in minimal cell yields of serial primary FNA cultures.

An additional 10 cases will be recruited for participation in the XEL intervention. FNA and/or urine samples will be assayed for compliance and biological feedback related to the reduction of phthalate and paraben intake through PCPs. In the final 3-months of the award, we will focus on data interpretation and further dissemination of study findings.

Scientific data acquired through this research could provide the rationale for expanding our population-based approach as a reliable means to predict potential carcinogenic effects of environmental chemicals directly within the human breast.