Postpartum mammary gland involution drives progression of ductal carcinoma in situ through collagen and COX-2

Nat Med. 2011 Aug 7;17(9):1109-15. doi: 10.1038/nm.2416.


The prognosis of breast cancer in young women is influenced by reproductive history. Women diagnosed within 5 years postpartum have worse prognosis than nulliparous women or women diagnosed during pregnancy. Here we describe a mouse model of postpartum breast cancer that identifies mammary gland involution as a driving force of tumor progression. In this model, human breast cancer cells exposed to the involuting mammary microenvironment form large tumors that are characterized by abundant fibrillar collagen, high cyclooxygenase-2 (COX-2) expression and an invasive phenotype. In culture, tumor cells are invasive in a fibrillar collagen and COX-2-dependent manner. In the involuting mammary gland, inhibition of COX-2 reduces the collagen fibrillogenesis associated with involution, as well as tumor growth and tumor cell infiltration to the lung. These data support further research to determine whether women at high risk for postpartum breast cancer would benefit from treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) during postpartum involution.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Analysis of Variance
  • Animals
  • Blotting, Western
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / physiopathology*
  • Carcinoma, Ductal / drug therapy
  • Carcinoma, Ductal / physiopathology*
  • Celecoxib
  • Cell Line, Tumor
  • Cyclooxygenase 2 / metabolism*
  • Disease Models, Animal*
  • Female
  • Fibrillar Collagens / metabolism*
  • Humans
  • Ibuprofen / pharmacology
  • Ibuprofen / therapeutic use
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Mammary Glands, Animal / drug effects
  • Mammary Glands, Animal / metabolism
  • Mammary Glands, Animal / physiology*
  • Mice
  • Mice, SCID
  • Neoplasm Invasiveness / physiopathology
  • Postpartum Period / drug effects
  • Postpartum Period / physiology*
  • Pregnancy
  • Pyrazoles / pharmacology
  • Pyrazoles / therapeutic use
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sulfonamides / pharmacology
  • Sulfonamides / therapeutic use


  • Fibrillar Collagens
  • Pyrazoles
  • Sulfonamides
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • Celecoxib
  • Ibuprofen