Systemic factors related to obesity, such as interleukin-6 receptor (IL-6R), leptin receptor (OB-R) and insulin-like growth factor-I receptor (IGF-IR), can inhibit the expression of ERβ in breast cancer cells through the pathway mediated by human epidermal growth factor receptor 2 (HER2) so that cancer cells can obtain greater cell activity, thus promoting their growth and worsening the prognosis of breast cancer (83). Here, ESR2 is linked to obesity due to melanocortin 4 receptor deficiency.