Oestrogen changes at menopause: insights into obesity-associated breast risk and outcomes.

This review synthesizes current evidence linking obesity, estrogen biology, inflammation, and postmenopausal breast cancer risk and progression.

Key points:

• • Obesity, inflamed adipose tissue, and immune dysfunction
  • In obesity, adipose tissue undergoes pre-adipocyte expansion and chronic activation of NF‑κB.
  • This drives production of pro‑inflammatory cytokines and creates a state of chronic low‑grade inflammation.
  • Obesity also impairs immunosurveillance, weakening anti-tumor immune responses.
• • Differential effects of pre- vs postmenopausal estrogens
  • Before menopause, 17β‑estradiol is the dominant estrogen and has anti‑inflammatory properties.
  • After menopause, oestrone becomes the dominant estrogen and is pro‑inflammatory.
  • Oestrone is synthesized in adipocytes; increased adipose mass in obesity elevates oestrone levels in both women and men.
  • Oestrone enhances NF‑κB–driven inflammation, providing a mechanistic link between obesity, inflammation, and cancer biology.
• • Oncogenic role of oestrone
  • Experimental models show that oestrone’s pro‑inflammatory effects are oncogenic, promoting breast cancer progression.
  • The shift from 17β‑estradiol to oestrone dominance, together with obesity-related inflammation, may help explain the higher incidence of hormone‑responsive breast cancer after menopause, especially in women with obesity.
• • Evidence gaps
  • Data on actual levels of 17β‑estradiol and oestrone in breast tissue and circulation of postmenopausal women are limited.
  • This applies both to women with and without obesity, constraining precise risk quantification and mechanistic clarity.
• • Clinical implications and weight loss
  • Weight loss is associated with reduced breast cancer risk and better outcomes.
  • The review highlights the potential to integrate potent pharmacologic weight‑loss agents as adjuncts to cancer therapy, aiming to modify the obesogenic, pro‑inflammatory, oestrone‑rich milieu that supports tumor growth.

Overall, the article frames postmenopausal, obesity‑associated breast cancer as driven by an interplay between inflamed adipose tissue, impaired immune control, and a shift toward pro‑inflammatory oestrone signaling.