Human breast cancer stem cells and sex hormones--a narrative review.

Objective: The aim of this narrative review was to evaluate the role of cancer stem cells (CSCs) and sex steroids in the pathophysiology of human breast cancer.

Methods: A key-word search was performed using the Scopus database. Preference was given to studies using human cells and tissues.

Results: Long-term estrogen-progestin hormone therapy is known to increase breast cancer risk, although the mechanisms are poorly understood. In the last few years, it has become clear that many human breast cancers contain CSCs, which may be responsible for much of the tumor's malignant behavior. Very recently, the impact of estrogen, progesterone, and progestins on breast CSCs and their progeny has been studied and clarified. Most breast CSCs are estrogen receptor negative and progesterone receptor negative, although some intermediary progenitor forms have hormone receptors, especially progesterone receptor. Most mature human breast cancer cellsare estrogen receptor positive and can thus be stimulated by estrogen. Breast CSCs usually elaborate CD44+,CD24j/low and/or ALDEFLUOR+ cell markers and are lineage markers negative. One of the main roles of progesterone and progestin seems to be on certain breast cancer stem intermediate forms, inducing them to revert back to a more primitive breast CSC form.

Conclusions: As the pathophysiology of human breast CSC is clarified, it is probable that this will lead to novel, effective breast cancer treatments and, perhaps, new breast cancer preventive agents. This research may also lead to safer hormone therapy regimens.