Mechanism and preclinical prevention of increased breast cancer risk caused by pregnancy

Svasti Haricharan, Jie Dong, Sarah Hein, Jay P. Reddy, Zhijun Du, Michael Toneff, Kimberly Holloway, Susan G. Hilsenbeck, Shixia Huang, Rachel Atkinson, Wendy Woodward, Sonali Jindal, Virginia F. Borges, Carolina Gutierrez, Hong Zhang, Pepper J. Schedin, C. Kent Osborne, David J. Tweardy, Yi Li

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

While a first pregnancy before age 22 lowers breast cancer risk, a pregnancy after age 35 significantly increases life-long breast cancer risk. Pregnancy causes several changes to the normal breast that raise barriers to transformation, but how pregnancy can also increase cancer risk remains unclear. We show in mice that pregnancy has different effects on the few early lesions that have already developed in the otherwise normal breast-it causes apoptosis evasion and accelerated progression to cancer. The apoptosis evasion is due to the normally tightly controlled STAT5 signaling going astray-these precancerous cells activate STAT5 in response to pregnancy/ lactation hormones and maintain STAT5 activation even during involution, thus preventing the apoptosis normally initiated by oncoprotein and involution. Short-term anti-STAT5 treatment of lactation-completed mice bearing early lesions eliminates the increased risk after a pregnancy. This chemoprevention strategy has important implications for preventing increased human breast cancer risk caused by pregnancy.

Original languageEnglish (US)
Article numbere00996
JournaleLife
Volume2013
Issue number2
DOIs
StatePublished - Dec 31 2013

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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    Haricharan, S., Dong, J., Hein, S., Reddy, J. P., Du, Z., Toneff, M., Holloway, K., Hilsenbeck, S. G., Huang, S., Atkinson, R., Woodward, W., Jindal, S., Borges, V. F., Gutierrez, C., Zhang, H., Schedin, P. J., Osborne, C. K., Tweardy, D. J., & Li, Y. (2013). Mechanism and preclinical prevention of increased breast cancer risk caused by pregnancy. eLife, 2013(2), [e00996]. https://doi.org/10.7554/eLife.00996