Does microenvironment contribute to the etiology of estrogen receptor-negative breast cancer?

What dictates the prevalence of certain types of breast cancer, which are classified by markers, particularly estrogen receptor (ER), expression profiles such as basal or luminal, and genetic alterations such as HER2 amplification, in particular populations is not well understood. It is increasingly evident that microenvironment disruption is highly intertwined with cancer progression. Here, the idea that microenvironment shapes the course of carcinogenesis, and hence breast cancer subtype, is discussed. Aggressive, basal-like, ER-negative breast tumors occur in younger women, African-American women, women who carry BRCA1 mutation, and women exposed to ionizing radiation. Recent experimental studies using ionizing radiation, a well-documented environmental exposure, suggest that certain processes in the microenvironment strongly favor the development of ER-negative tumors. Understanding the contribution of tissue microenvironment during carcinogenesis could lead to prevention strategies that are personalized to age, agent, and exposure to reduce the risk of aggressive breast cancer.