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

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...

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Bibliographic Details
Published in:eLife 2013-12, Vol.2, p.e00996
Main Authors: Haricharan, Svasti, Dong, Jie, Hein, Sarah, Reddy, Jay P, Du, Zhijun, Toneff, Michael, Holloway, Kimberly, Hilsenbeck, Susan G, Huang, Shixia, Atkinson, Rachel, Woodward, Wendy, Jindal, Sonali, Borges, Virginia F, Gutierrez, Carolina, Zhang, Hong, Schedin, Pepper J, Osborne, C Kent, Tweardy, David J, Li, Yi
Format: Article
Language:English
Subjects:
Age
Animals
Apoptosis
Breast cancer
Breast Neoplasms - complications
Breast Neoplasms - metabolism
Breast Neoplasms - prevention & control
Carcinogenesis
Cell Biology
Cell Division
chemoprevention
College campuses
Disease Models, Animal
Female
Health risk assessment
Human Biology and Medicine
Infections
Lactation
Medicine
Mice
Mutation
Oncogenes
Pregnancy
Pregnancy Complications, Neoplastic - metabolism
Pregnancy Complications, Neoplastic - prevention & control
Rodents
STAT5
Stat5 protein
STAT5 Transcription Factor - metabolism
Statistical analysis
Survival analysis
Tumorigenesis
Tumors
Womens health
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Summary: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. DOI: http://dx.doi.org/10.7554/eLife.00996.001.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.00996