A key paper published in 2003 by Al-Hajj et al. link prospectively identified and isolated tumor initiating cells (also called cancer stem cells) as CD44+CD24-/low Lin-neg from a series of plural effusions. Many studies have since used these markers. An unanswered question remains whether these markers identify tumor initiating cells, and whether a rare tumor initiating cell population exists, in all subtypes of breast cancer. It has always been my thought that different subtypes of breast cancer would have tumor initiating cells identified by different markers.

A recent paper was published in PNAS showing a rare CD44++ ER- PR- K5++ tumor initiating cell present in xenografts of T47D, a luminal subtype cancer cell line. Therefore, maybe some human luminal tumors (perhaps luminal B)contain rare steroid negative tumorigenic cells which would be expected to be refractory to endocrine therapy and could survive and repopulate the tumor.