Abstract PR06: Exposure to phthalates and risk of invasive breast cancer: The Multiethnic Cohort Study

Abstract

Abstract Background: Phthalates (Phth), known endocrine-disruptors, may play a role in breast carcinogenesis. Low-molecular-weight phthalates (LMWPhth) are commonly found in personal care products while high MWPhth (HMWPhth) are used primarily as plasticizers. Individual Phth may disrupt normal mammary gland development and promote tumorigenesis by binding to and activating the estrogen receptor (ER). Methods: We prospectively examined the association between pre-diagnostic urinary levels of Phth metabolites and breast cancer risk in a case-control study nested within the Multiethnic Cohort (MEC). We measured 11 Phth metabolites and phthalic acid from overnight/first morning urine samples of 798 women with invasive breast cancer (355 Japanese Americans, 218 Whites, 125 Native Hawaiians, 62 Latinos, and 38 African Americans; the latter three groups were combined due to small numbers) and 796 matched controls using an ultrasensitive isotope dilution orbitrap LCMS assay after hydrolysis from conjugation, extraction, and concentration. Average time between urine collection and breast cancer diagnosis was 5.5 years (SD=3.3). Cases and controls were 1:1 matched on area (Hawaii or California), birth year (± 1 year), race/ethnicity, urine type (overnight or first morning), and date of urine collection (± 1 year). Association of LMWPhth (MBP, MiBP, MEP, MMP), HMWPhth (MBzP, MEHP, MEHHP, MEOHP, MECPP, MCMHP, MCHP), and total Phth exposure (LMWPhth + HMWPhth), and phthalic acids with breast cancer risk were examined using conditional logistic regression. All models were adjusted for creatinine levels, demographics, and potential confounders (e.g., education and established breast cancer risk factors). Stratified analyses were conducted by race/ethnicity and ER and progesterone receptor (PR) status. Results: Women in the highest tertile (T3) of total Phth exposure showed a significant increased risk of breast cancer compared to women in the lowest tertile (T1) (HR=1.36, 95% CI: 1.02-1.82). The association was suggested across race/ethnicity with a statistically significant positive association observed in the three smaller groups combined (Native Hawaiians, Latinos, and African Americans) with HR for T2=2.29 (95% CI: 1.27-4.41) and HR for T3=2.42 (95% CI: 1.25-4.70); Ptrend=0.006. By ERPR status, risk associations tended to be stronger for ER-PR- (n=96 cases) (HR=1.13, 95% CI: 0.89-1.45) than for ER+PR+ (n=694 cases) (HR=1.06, 95% CI: 0.94-1.19) breast tumors. Among the three smaller groups combined, total Phth exposure was associated with a significant increased risk of ER-PR- breast cancer (n=38 cases) (P=0.045). Conclusion: This is one of the first studies of Phth exposure and breast cancer to include large numbers of diverse populations in a single study. Risk patterns were stronger among the combined group of Native Hawaiians, Latinos, and African American and for ER-PR- breast cancer. Better understanding of these differences in risk associations by race/ethnicity and ERPR status is needed. This abstract is also being presented as Poster D100. Citation Format: Anna H. Wu, Adrian A. Franke, Chiuchen Tseng, Shannon M. Conroy, Yuqing S. LI, Mindy DeRouen, Linda Polfus, Christian Caberto, Daniel Stram, Chris Haiman, Lynne R. Wilkens, Loic Le Marchand, Iona Cheng. Exposure to phthalates and risk of invasive breast cancer: The Multiethnic Cohort Study [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr PR06.