A comparison of breast cancer biopsies before and after treatment show that a subset of cells, which have stem cell-like properties, are resistant to standard chemotherapy. Tumors treated with lapatinib, which inhibits a pathway important for self-renewal, retained a smaller fraction of these tumorigenic cells after therapy.
Several research groups have identified a subset of cells in breast tumors that have the ability to form colonies in culture and give rise to tumors in mouse models. These cells, which express CD44 protein on their surface but little or no CD24 (CD44+/CD24-/low), are frequently referred to as cancer stem cells and may be resistant to standard chemotherapeutic agents. Lapatinib, which is approved for treatment of HER2-positive breast cancer, inhibits the HER2 pathway. The drug also inhibits the epidermal growth factor receptor pathway, which may be important for stem cell proliferation.
To find out how the CD44+/CD24-/low cells respond to cytotoxic chemotherapy, Jenny Chang, M.D., from the Baylor College of Medicine in Houston and colleagues compared breast cancer biopsy samples taken from patients before and after standard chemotherapy or lapatinib therapy.
After chemotherapy, the fraction of CD44+/CD24-/low cells increased in 31 paired biopsy samples, from a mean of 4.7 percent at baseline to 13.6 percent after 12 weeks of therapy. Biopsy samples taken after chemotherapy were also more efficient at forming mammospheres, an indication of self-renewal, when grown in culture. By contrast, there was a decrease in the proportion of CD44+/CD24-/low cells in biopsies from 21 women treated with lapatinib, from 10 percent to 7.5 percent.
"Results of this study are encouraging and suggest that inhibition of key regulatory pathways responsible for self-renewal could augment the effects of conventional therapy and improve clinical outcome," the authors write.
This research was reported April 29 in the Journal of the National Cancer Institute.