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Comprehensive Literature Review Confirms Etiologic Heterogeneity by Breast Cancer Subtype

, by Maura Kate Costello, M.A.

Multiple journals on a shelf.

Improved understanding of the role various risk factors play in the development of breast cancer subtypes and whether that role differs by race and ethnicity is critical for advancing disease prevention and early detection, particularly for tumor subtypes associated with low survival, which remain major contributors to breast cancer mortality globally. Investigators conducted a qualitative, scoping review of the literature published between January 1, 1990, and July 1, 2022, and found evidence to support etiologic heterogeneity by estrogen receptor (ER) subtype for some risk factors, which was consistent across racial and ethnic groups. This review, the largest, most comprehensive of its kind, was published on July 17, 2024, in the Journal of the National Cancer Institute

To conduct this study, Amber Hurson, Ph.D., M.P.H., staff scientist in the Integrative Tumor Epidemiology Branch, and colleagues assessed consistencies in associations between 18 breast cancer risk factors (reproductive, anthropometric, lifestyle, and medical history) and risk of ER defined subtypes in women who self-identify as Asian, Black or African American, Hispanic or Latina, or White. Starting with 6,517 articles, 219 articles passed eligibility requirements and were selected for review, representing 135 different study populations. The investigators found evidence that breast cancer etiologic heterogeneity by ER was strongest for parity (the number of times a woman has given birth), followed by age at first birth, post-menopausal BMI, oral contraceptive use, and estrogen-only and combined menopausal hormone therapy. These findings were consistent across racial and ethnic groups, though strength of evidence varied.  

To address shortcomings in the current body of literature, this review highlights the need for large, high-quality epidemiological studies on etiologic heterogeneity across breast cancer subtypes in diverse populations with comprehensive and standardized data on risk factors and pathology subtypes, as well as greater adoption of FAIR (findable, accessible, interoperable, and reusable) data principles to improve reproducibility of findings and to facilitate data pooling across studies. Beyond ER status, incorporating other molecular markers (e.g., histologic grade, Ki67, or TP53 mutation status) into breast cancer subtyping schema may be warranted to characterize etiologic subtypes of breast cancer with epidemiologic and public health relevance. Additional studies evaluating possible heterogeneity in subtype-specific risks across racial and ethnic groups are needed, especially those that account for social variables that may modify risk and that differ by race or ethnicity.  

Reference

Hurson AN, et al. Risk factors for breast cancer subtypes by race and ethnicity: A scoping review. J Natl Cancer Inst. 2024. 

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