Debate: The Biology of Breast Cancer in Young Women Is Unique

Abstract

There is no question that breast cancer arising in young women is unique in many aspects. Challenges faced by young women diagnosed with breast cancer are often quite different than those experienced by older women. These unique challenges may include disruption of career in its early phase, child-bearing and ongoing family responsibilities, impact of therapy on sexuality and body image, and the psychosocial toll of facing a life-threatening illness at a young age. Historically, multiple studies have shown that younger women tend to experience worse breast cancer outcomes as compared to older counterparts, however the reason for this observation is not entirely known. Studies have also shown that the more aggressive subtypes of breast cancer (i.e. basal-like and HER2-enriched) are over-represented among younger women aged ≤45 years as compared to older women aged ≥65 years. Taking a more detailed view of the biology of young women's breast tumors using gene expression data from several large, publically-available data sets in a non-subtype-dependent manner, breast tumors arising in younger women were enriched for ≥350 biologically-relevant gene sets and hundreds of individual genes compared to older women. However, when adjusting for significant clinicopathologic features including grade and subtype, adjusted models yielded negligible gene differences between breast tumors arising from defined age groups of ≤45versus ≥65 years - a finding that was validated in an independent dataset. This data argues that the biology of young women's breast tumors may not be unique, but rather that the overrepresentation of aggressive subtypes is accounting for disparities in outcome by age. While this information is compelling, many unanswered questions remain including (1)why are younger women more prone to aggressive subtypes of breast cancer, (2) what is the role of the microenvironment, (3) how does breast density and/or other factors (i.e. breast-feeding, parity) contribute to these findings and (4) will disparities in outcome persist in the era of modern targeted therapies - all areas deserving of further research.