Phthalate Metabolites and Breast Cancer Risk in the Women's Health Initiative

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 DESCRIPTION (provided by applicant): Mounting laboratory and animal model evidence supports the potentially carcinogenic effects of phthalates, chemicals used as plasticizers in a wide variety of consumer products (e.g. cosmetics, medications, vinyl flooring). Phthalate metabolites are measurable in nearly 100% of the U.S. population, though levels vary widely, and also have been reported in human breast milk. However, data on whether phthalates affect human breast cancer risk is lacking. Only one small retrospective case-control study exists, which reported a two-fold increase in breast cancer risk associated with urinary levels of mono-ethyl phthalate, yet either no association or an inverse association with other phthalate metabolites studied. Retrospective studies utilizing a single urine sample are poorly suited for addressing this important question, because 1) urinary phthalate metabolite levels measured after diagnosis may have been affected by phthalate exposure during treatment, and 2) a single measurement is unlikely to reflect longer-term exposures, which are of greater relevance to cancer risk. As a result, the impact of phthalate exposure on breast cancer risk remains poorly understood. Clarifying the effects of these common exposures will provide critical information for the millions of women concerned about their breast health. We propose a prospective study nested within the Women's Health Initiative (WHI) to evaluate associations between levels of eleven urinary phthalate metabolites and breast cancer risk. Prospectively collected urine samples from baseline and year 3 of follow-up are available on a sub-sample of WHI participants with year 1 urine samples also available on some participants. Extensive data from questionnaires and medical records, including known breast cancer risk factors, also are available on these participants. We will measure levels of eleven phthalate metabolites in repeated urine samples from 500 invasive breast cancer cases diagnosed after year 3 of follow-up and 1,000 healthy matched controls to address the following Specific Aims: 1) to determine if phthalate metabolite levels are associated with breast cancer risk, and 2) to evaluate if the associations between phthalate metabolite levels and breast cancer vary by: a) disease characteristics such as hormone receptor status; and b) personal factors including age, postmenopausal hormone therapy use, and body mass index. The stored repeat urine samples and vast accompanying data available within the prospective WHI cohort are a unique resource and provide an excellent opportunity to explore for the first time the role of phthalates in breast cancer risk. If a link between phthalates and breast cancer risk were observed, women could reduce their exposure to phthalate-containing consumer products as a means of primary prevention. Ultimately, understanding if exposure to phthalates affects breast cancer risk may motivate manufacturer, legislative, and advocacy efforts to remove phthalates from consumer products altogether.