AS458 - Phthalate metabolites and breast cancer risk in the Women's Health Initiative

Investigator Names and Contact Information

Katherine Reeves (kwreeves@umass.edu)

Introduction/Intent

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 are conducting a prospective study nested within the Women's Health Initiative (WHI) to evaluate associations between levels of thirteen 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 thirteen phthalate metabolites in repeated urine samples from 419 invasive breast cancer cases diagnosed after year 3 of follow-up and 838 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.

Related Papers

Association between phthalate exposure and body composition among postmenopausal women.

Approved Proposal, Diaz-Santana, Mary V. et al., 2018/5 MSID: 3639
Related Studies: 458

Mixtures analysis of phthalate exposure and breast cancer risk in the WHI

Approved Proposal, Mascari, Michael et al., 2020/10 MSID: 4320
Keywords: Phthalates; Breast Cancer; Mixtures; Endocrine Disrupting Chemicals
Related Studies: 458

Prospective evaluation of phthalate biomarker exposure and adjudicated cardiovascular disease among participants of the Women’s Health Initiative Study

Approved Proposal, Vieyra, Gabriela et al., 2021/10 MSID: 4499
Keywords: Cardiovascular Disease; Phthalate Biomarkers; Adjudicated; Survival Analysis; Postmenopausal
Related Studies: 458

Predicting phthalate bio-burden through medication and dietary supplement exposure

Approved Proposal, Ahern, Thomas et al., 2016/3 MSID: 3003
Keywords: Breast Neoplasms; Epidemiology; Predictive Models; Phthalates; Pharmacoepidemiology
Related Studies: 458

Biomarkers of phthalates and inflammation: Findings from a subgroup of Women’s Health Initiative participants

Avery Trim et al., 2021/4 PubMed #33813346 MSID: 4029
Background: Recent experimental work has shown that phthalates may increase inflammation. Prior research has not examined the role of exposure to phthalates in relation to inflammatory status among postmenopausal women who are at higher risk of developing inflammation-related chronic disorders. Objectives: We aimed to examine the associations of urinary phthalate biomarker concentrations with circulating levels of c-reactive protein [CRP] and interleukin-6 [IL-6] among 443 postmenopausal women s...
Keywords: Phthalates; Inflammation; Cytokines; Crp; Tnf-A; Interleukins
Related Studies: 458

Predictors of urinary phthalate biomarker concentrations in postmenopausal women

Katherine Reeves et al., 2018/10 PubMed #30447499 MSID: 3470
Abstract BACKGROUND: Phthalates are ubiquitous endocrine disrupting chemicals present in a wide variety of consumer products. However, the personal characteristics associated with phthalate exposure are unclear. OBJECTIVES: We sought to describe personal, behavioral, and reproductive characteristics associated with phthalate metabolite concentrations in an ongoing study nested within the Women's Health Initiative (WHI). MATERIALS AND METHODS: We measured thirteen phthalate metabolites in two or ...
Keywords: Phthalates; Descriptive; Behavioral Factors; Predictors; Reproductive Factors
Related Studies: 458

Dietary patterns and urinary phthalate exposure among postmenopausal women of the Women’s Health Initiative

Gabriela Vieyra et al., 2022/11 PubMed #36356671 MSID: 4082
Background: Phthalates are endocrine-disrupting chemicals linked to a higher risk of numerous chronic health outcomes. Diet is a primary source of exposure, but prior studies exploring associations between dietary patterns and phthalate exposure are limited. Objectives: We evaluated the associations between dietary patterns and urinary phthalate biomarkers among a subset of postmenopausal women participating in the Women's Health Initiative (WHI). Methods: We included WHI participants selected f...
Keywords: Dietary Inflammation Index (Dii); Dietary Approach To Stop Hypertension (Dash); Alternative Mediterranean Diet (Amed); Phthalate Biomarkers; Dietary Pattern
Related Studies: 458

Association between urinary phthalate biomarker concentrations and adiposity among postmenopausal women

Katherine Reeves et al., 2023/1 PubMed #36706896 MSID: 4129
Background: Obesity is a leading risk factor for chronic diseases, potentially related to excess abdominal adiposity. Phthalates are environmental chemicals that have been suggested to act as obesogens, driving obesity risk. For the associations between phthalates and adiposity, prior studies have focused primarily on body mass index. We hypothesize that more refined measures of adiposity and fat distribution may provide greater insights into these associations given the role of central adiposit...
Keywords: Phthalates; Adiposity; Prospective; Obesity
Related Studies: 458, 554

Urinary phthalate biomarker concentrations and postmenopausal breast cancer risk

Katherine Reeves et al., 2019/1 PubMed #30629220 MSID: 2889
Background: Growing laboratory and animal model evidence supports the potentially carcinogenic effects of some phthalates, chemicals used as plasticizers in a wide variety of consumer products, including cosmetics, medications, and vinyl flooring. However, prospective data on whether phthalates are associated with human breast cancer risk are lacking. Methods: We conducted a nested case-control study within the Women's Health Initiative (WHI) prospective cohort (N = 419 invasive cases and 838 co...
Keywords: Phthalates; Breast Cancer; Cancer Risk; Er Status; Pr Status
Related Studies: 458

Urinary concentrations of phthalate biomarkers and weight change among postmenopausal women: a prospective cohort study

Mary V. Diaz-Santana et al., 2019/3 PubMed #30866962 MSID: 2890
BACKGROUND: Some phthalates are endocrine disrupting chemicals used as plasticizers in consumer products, and have been associated with obesity in cross-sectional studies, yet prospective evaluations of weight change are lacking. Our objective was to evaluate associations between phthalate biomarker concentrations and weight and weight change among postmenopausal women. METHODS: We performed cross-sectional (N = 997) and longitudinal analyses (N = 660) among postmenopausal Women's Health Initiat...
Keywords: Phthalates; Weight; Fat Mass; Lean Mass; Obesity
Related Studies: 458

Urinary phthalate biomarkers and bone mineral density in postmenopausal women

Katherine Reeves et al., 2021/3 PubMed #33754148 MSID: 3134
Background: Phthalates are endocrine-disrupting chemicals that could disrupt normal physiologic function, triggering detrimental impacts on bone. We evaluated associations between urinary phthalate biomarkers and BMD in postmenopausal women participating in the prospective Women's Health Initiative (WHI). Methods: We included WHI participants enrolled in the BMD substudy and selected for a nested case-control study of phthalates and breast cancer (N=1255). We measured thirteen phthalate biomarke...
Keywords: Phthalates; Bone; Endocrine Disruption; Bone Mineral Density
Related Studies: 458