After testing 52 human BC cell lines, we selected two lines based on SN-38 sensitivity, TOP1 gene copy status, HER2 status and estrogen receptor protein expression, and used these two cell lines to develop SN-38 resistance by either exposing them to stepwise increasing concentrations of SN-38 over a period of 6 months or by selecting the cell population that survived exposure to the highest SN-38 concentration. The gene discussed is TOP1; the disease is breast cancer.