The growth hormone receptor antagonist pegvisomant blocks both mammary gland development and MCF-7 breast cancer xenograft growth

Breast Cancer Res Treat. 2006 Aug;98(3):315-27. doi: 10.1007/s10549-006-9168-1. Epub 2006 Mar 16.


Mammary gland development is dependent upon the growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis, this same axis has also been implicated in breast cancer progression. In this study we investigated the effect of a GH antagonist, pegvisomant (Somavert, Pfizer), on normal mammary gland development and breast cancer xenograft growth. Intraperitoneal administration of pegvisomant resulted in a 60% suppression of hepatic IGF-I mRNA levels and upto a 70-80% reduction of serum IGF-I levels. Pegvisomant administration to virgin female mice caused a significant delay of mammary ductal outgrowth that was associated with a decrease in the number of terminal end buds and reduced branching and complexity of the gland. This effect of pegvisomant was mediated by a complete inhibition of both GH and IGF-IR-mediated signaling within the gland. In breast cancer xenograft studies, pegvisomant caused shrinkage of MCF-7 xenografts, with an initial 30% reduction in tumor volume, which was associated with a 2-fold reduction in proliferation and a 2-fold induction of apoptosis. Long-term growth inhibition of MCF-7 xenografts was noted. In contrast, pegvisomant had no effect on MDA-231 or MDA-435 xenografts, consistent with primary growth of these xenografts being unresponsive to IGF-I both in vitro and in vivo. In MCF-7 xenografts that regressed, pegvisomant had only minor effects upon GHR and IGF-IR signaling. This data supports previous studies indicating a role for GH/IGF in mammary gland development, and suggests that pegvisomant maybe useful for the prevention and/or treatment of estrogen receptor positive breast cancer.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Human Growth Hormone / analogs & derivatives*
  • Human Growth Hormone / pharmacology
  • Humans
  • Insulin-Like Growth Factor I / metabolism
  • Mammary Glands, Human / metabolism
  • Mice
  • Neoplasm Transplantation
  • Receptor, IGF Type 1 / metabolism
  • Receptors, Estrogen / metabolism
  • Receptors, Somatotropin / antagonists & inhibitors*


  • Antineoplastic Agents
  • Receptors, Estrogen
  • Receptors, Somatotropin
  • Human Growth Hormone
  • Insulin-Like Growth Factor I
  • Receptor, IGF Type 1
  • pegvisomant