Impact of Reducing Chemical Exposure to the Human Breast

Institution: Breast Cancer Over Time
Investigator(s): Polly Marshall, JD - Shanaz Dairkee, Ph.D. -
Award Cycle: 2015 (Cycle 21) Grant #: 21AB-1400 Award: $26,180
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-1401 -

Final Report (2017)

This pilot research project is a collaborative effort with breast cancer survivor community members for recruitment and support of volunteers participating in a XE (xenoestrogen)-low (XEL) intervention through the use of XE-free personal care products (PCPs). To facilitate improvements in human breast toxicology, our study is the first to integrate a broad range approach, including: volunteer participation, serial fresh sample acquisition, monitoring compliance with study requirements, laboratory expansion of live healthy breast cells collected by fine needle aspiration (FNA), and molecular and functional analysis of study-related samples to evaluate biological shifts resulting from a reduced XE regimen adopted by each test subject.

The feasibility of our project goals is consistently demonstrated by the following major accomplishments: (a) dissemination of the study design in well-attended public forums enabling screening of informed community volunteers, (b) timely recruitment of 24 pre- and post-menopausal volunteers into the study, who consented to participating in the proposed healthy intervention and to providing serial samples of blood, urine, and normal breast tissue FNA, (c) determination of study compliance by volunteers monitored by phthalate and paraben metabolite levels in post-XEL urine samples with statistically significant reductions observed for mono-(2-ethylhexyl)-phthalate (p=0.02), and the paraben metabolites - butyl, ethyl, and methylparaben (p=0.04, 0.008, and 0.03, respectively) without statistically significant changes for estrogen (E2), progesterone (Pg), and sex hormone binding globulin levels (SHBG), (d) verification of self-reported length of menstrual cycle in pre-menopausal subjects, as shown by blood chemistry before and after 28-day XEL, (e) robust in vitro expansion of pre- and post-XEL intervention healthy breast tissue FNA for conducting relevant laboratory assays represented by live cell yields from 75% of FNA samples collected, (f) application of serial primary FNA cultures towards multiplexed analysis of estrogen receptor (ER) isoforms to detect measurable shifts in post-intervention levels with up to 69% reduction in the cell proliferation promoting isoform - ER alpha, and up to 187% increase in the inhibitory isoform - ER beta, (g) analysis of the functional status of pre- and post-intervention live breast cells using parameters such as programmed cell death and cell cycle progression (widely accepted as regulated by estrogen-mediated molecular signaling), demonstrating up to 50% decline in cell proliferation rate, and accompanying S-phase fraction, as well as a concurrent, up to 35%, improvement in the efficiency of experimentally-induced programmed cell death.

The timely implementation of our study goals allayed several concerns regarding subject participation. We successfully recruited both pre- and post-menopausal women; achieved compliance for 15 and 28-day intervention periods; had 100% attendance at scheduled visits to the sample collection study site; and observed ready acceptance of the relatively invasive FNA sample collection experience. Concurrently, extending the use of minimal samples of breast tissue to generate meaningful laboratory assay material was a significant challenge, but in our hands proved to be a pragmatic and fruitful endeavor. Thus far our cumulative data strongly suggest that a proactive reduction in the use of paraben and phthalate-containing PCPs by study subjects resulted in a ‘normalized, less cancer-prone ‘ biological profile of breast tissue-derived live cells. Altogether, this pilot study provides a strong rationale for expanding such a population-based approach to a larger recruitment and research effort to obtain adequate statistical power for validating the novel insights obtained here. Through the application of such innovative community-research partnerships, the possibility of expediting the direct relevance of safety evaluations for the multitude of chemicals within common consumer-use products to human breast health now appears within reach.