**3. Conclusion**

A new concept of sex epigenome begins to emerge. In addition to gonadal hormones, the copy number difference of the X chromosome between males and females contributes to sex differences in BC - an extra copy of the X chromosome confers a better protection of females. Moreover, there is a cooperative interaction between the sex hormones and chromosomes during BC development. The tumor suppressing effect of the X chromosome is largely mediated by *KDM6A-*dependent epigenetic program, or the sex epigenome. The sex chromosome, sex chromosome, and sex epigenome collectively contribute to sex differences in BC.
