Table 3 Key points

Women experience approximately 500 menstrual cycles (MCs) during the 40 years of their reproductive life, and there is a high correlation between the actual number of MCs and the lifetime risk of developing breast cancer (BC)

A reduction in MCs due to physiological, genetic and pathological effects reduces the BC risk in proportion with the decrease in the number of MCs

Progesterone (P4), rather than estradiol (E2), profoundly stimulates proliferation of the breast epithelium during the luteal phase of the MC through the paracrine factors WNT4 and RANKL and by inducing the expression of the ‘DNA mutator’ APOBEC3B, thereby enhancing the risk of developing BC

Estrogens (E) hardly stimulate normal estrogen receptor positive (ER⁺) breast epithelial cells, but have a strong proliferative effect on neoplastic ER⁺ cells