Table 1.

Summary of Human Studies on Paraben Exposure and Breast Cancer.

	Conclusions	Strength	Limitations
Darbre et al. 2004 [19].	Intact parabens were found in the human breast tumor tissues. MP was present at the highest level and represented 62% of the total parabens extracted from breast tumor tissues.	Demonstrated that after exposure, a proportion of the parabens can remain intact in human body tissues. The levels of parabens measured in this study were comparable to the levels of parabens used in in vitro studies, indicating the levels of parabens detected in breast tissues could induce estrogenic effects in the human breast.	Small sample size. Analytical blank values might contain parabens introduced from other sources.
Barr et al. 2011 [32].	Parabens were detected across the human breast from axilla to sternum. PP was found at significantly higher levels in the axilla than mid or medial regions of the breast. No correlations were found between paraben concentrations and tumor location or tumor estrogen receptor content.	Measured at the earliest time point possible after cancer diagnosis and prior to any cancer therapy. Investigated the distribution of parabens across a single breast.	Parabens were detected in breast tissues from human subjects who self-reported as non-underarm cosmetics users. Parabens were measured from breast tissues adjacent to breast tumor but not from tumor directly. It is also unclear the relative importance of long-term accumulation and/or acute exposure to the levels of parabens in the breast tissue.
Sprague et al. 2013 [34].	Serum concentrations of BP and PP were modestly correlated, but parabens concentrations were not associated with percentage breast density (a marker of breast cancer risk).	Evaluated mammographic breast density in relation to biological measures of xenoestrogens, including parabens. Serum measurements may better reflect the biologically relevant exposure of the target organs.	Only postmenopausal women were enrolled in the study. Single blood sample was collected, which may only reflect current exposure. The study population was predominately non-Hispanic white. The results may not apply to general population.
Harley, et al. 2019 [30].	Peripubertal concentrations of MP were associated with earlier breast development, pubic hair development, and menarche in girls; peripubertal concentrations of PP were associated with earlier pubic hair development in girls; peripubertal PP concentrations were associated with earlier genital development in boys.	Evaluated prenatal as well as peripubertal parabens exposure.	Urinary parabens only reflected recent exposure. The study population was limited to Latino women and children of low socioeconomic status. Potential confounding factors from other environmental contaminants could not be ruled out. Associations of peripubertal measurements with parabens may reflect reverse causality because children going through puberty earlier may be more likely to use personal care products.
Parada et al. 2020 [35].	The highest (vs. lowest) quintiles of urinary MP, PP, and total parabens were associated with the risk of breast cancer. MP, PP, and total parabens were inversely associated with all-cause mortality hazard ratios.	A case-control and follow up design. Large sample size. Participants included women with breast cancer and women without breast cancer. Among women with breast cancer, phenol biomarkers were quantified in urine samples. Women with breast cancer were monitored for vital status with a median follow-up of 17.6 years. Examined whether urinary phenol biomarkers were associated with mortality following breast cancer.	A single spot urine sample may not be a reliable reflection of women’s parabens exposure. In addition, urine samples from breast cancer patients were collected after not before their diagnosis.
Wu et al. 2021 [36].	Breast cancer risk was weakly inversely associated with total (but not individual) parabens exposure. Risk of hormone receptor positive (HR+) cancer was lower among women in the upper two tertiles of paraben exposure.	A multiethnic population-based nested case-control study. Examined the association between breast cancer risk and prediagnostic exposures paraben. Potential differences in terms of hormone receptor status, tumor stage (invasive vs in situ) and the length of follow-up time were considered in the analysis.	All cases and controls were postmenopausal at the time of urine collection. A single measure of parabens to capture long-term exposures could lead to misclassification of exposure.