Systemic Spread Is an Early Step in Breast Cancer

Cancer Cell. 2008 Jan;13(1):58-68. doi: 10.1016/j.ccr.2007.12.003.

Abstract

It is widely accepted that metastasis is a late event in cancer progression. Here, however, we show that tumor cells can disseminate systemically from earliest epithelial alterations in HER-2 and PyMT transgenic mice and from ductal carcinoma in situ in women. Wild-type mice transplanted with single premalignant HER-2 transgenic glands displayed disseminated tumor cells and micrometastasis in bone marrow and lungs. The number of disseminated cancer cells and their karyotypic abnormalities were similar for small and large tumors in patients and mouse models. When activated by bone marrow transplantation into wild-type recipients, 80 early-disseminated cancer cells sufficed to induce lethal carcinosis. Therefore, release from dormancy of early-disseminated cancer cells may frequently account for metachronous metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / pathology
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology*
  • Cell Proliferation
  • Cell Transformation, Neoplastic
  • Epithelial Cells / pathology
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Karyotyping
  • Lung Neoplasms / secondary
  • Mammary Glands, Animal / transplantation
  • Mammary Glands, Animal / ultrastructure
  • Mammary Neoplasms, Experimental / genetics
  • Mammary Neoplasms, Experimental / pathology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplastic Cells, Circulating / pathology
  • Precancerous Conditions / genetics
  • Precancerous Conditions / pathology*
  • Siblings