# Invited Perspective: Deciphering the Role of Endocrine Disruptors in Cancer—
Challenges and Opportunities for Epidemiological Research

Claire Philippat¹

¹University Grenoble Alpes, Inserm U-1209, CNRS-UMR-5309, Environmental Epidemiology Applied to Reproduction and Respiratory Health Team, Institute for Advanced Biosciences, Grenoble, France

https://doi.org/10.1289/EHP14568

Refers to https://doi.org/10.1289/EHP13882

Endocrine-disrupting chemicals (EDCs) are recognized for their potential impact on hormonal signaling, presenting a plausible link to various diseases, including certain types of cancer.¹,² Hormones play important roles in some cancer development, progression, and survival. This is the premise behind the work of Goldberg et al., published in this issue of *Environmental Health Perspectives*,³ which provides valuable insights into the possible relationship between exposure to EDCs during adolescence, specifically through the use of personal care products, and the later development of breast cancer. However, this study also underscores the inherent challenges in investigating the carcinogenic effects of EDCs in human populations.

Significant hurdles are involved in conducting comprehensive studies to assess the carcinogenic effects of EDCs. An ideal study design requires large prospective cohorts recruited during early life, with a prolonged follow-up, recognizing that sensitive windows of exposure might occur decades before disease onset. Biobanking also plays a pivotal role because, given the diverse sources and pathways of EDC exposure, biomarkers measured in relevant biospecimens remain the gold standard for exposure assessment. Yet many contemporary EDCs exhibit short half-lives and, unlike persistent chemicals, moderate-to-high within-subject temporal variability.⁴ Thus, biospecimens collected nearer to cancer diagnosis may inadequately reflect exposures during critical periods, such as adolescence.

Regrettably, owing to practical constraints and cost limitations, this optimal study setup is rare in epidemiological studies on environmental risk factors for breast cancers. Often, studies rely solely on questionnaires to evaluate EDC exposure during crucial developmental stages. Despite their ability to circumvent recall bias (i.e., differential response between cases and controls) if they precede the cancer diagnosis, questionnaires usually are retrospective and thus remain susceptible to measurement errors. In addition, efforts to account for all sources and pathways of EDC exposure through exhaustive questionnaires might overwhelm participants, leading to substantial loss of follow-up,

missing data, and challenges for the research team in aggregating complex exposure data.

Therefore, some studies, such as the new work by Goldberg et al., focus on single exposure sources, such as personal care products, many of which contain both EDCs (e.g., some phthalates⁵) and carcinogenic compounds (e.g., formaldehyde⁶). Although such an approach reduces participant burden, it presents limitations, given that it provides information on only a fraction of the total exposure by overlooking other sources. It also may be subject to residual confounding (e.g., the quantity and types of products used may be associated with other risk factors for breast cancer).

Moreover, personal care products comprise multiple chemicals. Their composition varies across brands and over time, impeding the identification of specific chemicals responsible for observed effects. Identifying these specific agents is pivotal for enacting effective legislation—which is typically carried out on a per-substance basis—and for protecting public health. The variation in composition between types of personal care products may also partly explain why Goldberg et al. identified no associations between product use patterns and incident breast cancer using the latent class approach, although they did find associations with a few specific personal care products.

The absence of strong conclusive associations in the study by Goldberg et al. does not diminish the relevance of investigating the EDC-cancer nexus. Rather, it emphasizes the critical need for meticulously designed studies incorporating biospecimen collection at critical time points. Although challenging, such endeavors are not impossible; however, they demand long-term commitment, substantial resources, and unwavering support to navigate follow-up, sample storage, and chemical assessments. Drawing definitive conclusions from these studies will require time.

Intervention studies limiting the use of personal care products have demonstrated that such behavioral changes lead to a decreased body burden of EDCs.⁷ Pending more conclusive evidence about the carcinogenicity of EDCs, limiting the use of non-essential personal care products could serve as a precautionary approach.

## References

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2. Bokobza E, Hinault C, Tiroille V, Clavel S, Bost F, Chevalier N. 2021. The adipose tissue at the crosstalk between EDCs and cancer development. Front Endocrinol (Lausanne) 12:691658, PMID: 34354670, https://doi.org/10.3389/fendo.2021.691658.

3. Goldberg M, Chang CJ, Ogunsina K, O'Brien KM, Taylor KW, White AJ, et al. 2024. Personal care product use during puberty and incident breast cancer among Black, Hispanic/Latina, and White women in a prospective US-wide cohort. Environ Health Perspect 132(2):027001, https://doi.org/10.1289/EHP13882.

4. Casas M, Basagaña X, Sakhi AK, Haug LS, Philippat C, Granum B, et al. 2018. Variability of urinary concentrations of non-persistent chemicals in pregnant

Address correspondence to Claire Philippat, Institut pour l'Avancée des Biosciences, Centre de Recherche UGA/Inserm U 1209/CNRS UMR 5309, Site Santé – Allée des Alpes, 38700 La Tronche, France. Email: claire.philippat@inserm.fr

The author declares she has no conflicts of interest related to this work to disclose.

Conclusions and opinions are those of the individual authors and do not necessarily reflect the policies or views of EHP Publishing or the National Institute of Environmental Health Sciences.

Received 3 January 2024; Accepted 4 January 2024; Published 2 February 2024.

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