PD847 - TIRZEPATIDE, ESTROGEN MODULATION AND BREAST CANCER RISK: A NARRATIVELITERATURE REVIEW

PD847

TIRZEPATIDE, ESTROGEN MODULATION AND BREAST CANCER RISK: A NARRATIVE

LITERATURE REVIEW

L. De Carli¹, D. Bonfanti^1,*, M. Zanardi¹, A. Pezzana¹

¹Clinical Nutrition, ASL Città di Torino, Turin, Italy

Rationale: Obesity-related hyperinsulinemia, chronic inflammation and increased aromatase activity in adipose tissue enhance estrogen exposure and contribute to hormone receptor–positive breast cancer (BC) risk. Estrogen receptor (ER) signalling is central to BC development and progression. Tirzepatide, a GLP-1 and GIP receptor agonist, induces substantial weight loss, but its impact on estrogen-related pathways relevant to BC remains incompletely defined.

Methods: We conducted a structured literature review of PubMed up to January 2026, identifying studies linking tirzepatide to estrogen metabolism, adipose tissue distribution and ER signalling.

Results: In obesity tirzepatide achieved mean weight loss of approximately 20–22% with marked fat-mass reduction, implying a substantial decrease in peripheral aromatase substrate and thus potential lowering of systemic estrogen exposure.
GLP-1 receptor agonists directly regolate adipocyte function, reduce inflammatory adipokines and modulate the interactions with estrogen signalling in metabolic tissues. In obese mouse models of BC, tirzepatide-induced weight and adipose reduction paralleled suppression of tumor growth, supporting a link among adiposity, metabolic dysregylation, and tumor biology. In postmenopausal women, concomitant menopausal hormone therapy appears to enhance tirzepatide-associated weight loss, further highlighting estrogen–incretin crosstalk. No human study has yet demonstrated a direct effect of tirzepatide on ER expression or signalling in breast tissue.

Conclusion: Current evidence suggests that tirzepatide modulates estrogen exposure mainly indirectly, via profound reductions in adiposity, insulin resistance and inflammatory signalling rather than through direct ER targeting. These findings support further evaluation of tirzepatide as a metabolic tool to modify estrogen-driven BC risk in women with obesity.

Disclosure of Interest: None declared