Triple-negative breast cancer (TNBC) cells overexpress the epidermal growth 
factor receptor (EGFR). Nuclear EGFR (nEGFR) drives resistance to anti-EGFR 
therapy and is correlated with poor survival in breast cancer. Inhibition of 
EGFR nuclear translocation may be a reasonable approach for the treatment of 
TNBC. The anti-malarial drugs chloroquine and primaquine have been shown to 
promote an anticancer effect. The aim of the present study was to investigate 
the effect and mechanism of chloroquine- and primaquine-induced apoptosis of 
breast cancer cells. We showed that primaquine, a malaria drug, inhibits the 
growth, migration, and colony formation of breast cancer cells in vitro, and 
inhibits tumor growth in vivo. Primaquine induces damage to early endosomes and 
inhibits the nuclear translocation of EGFR. Primaquine inhibits the interaction 
of Stat3 and nEGFR and reduces the transcript and protein levels of c-Myc. 
Moreover, primaquine and chloroquine induce the apoptosis of breast cancer cells 
through c-Myc/Bcl-2 downregulation, induce early endosome damage and reduce 
nEGFR levels, and induce apoptosis in breast cancer through 
nEGFR/Stat3-dependent c-Myc downregulation. Our study of primaquine and 
chloroquine provides a rationale for targeting EGFR signaling components in the 
treatment of breast cancer.