title: Mechanism and preclinical prevention of increased breast cancer risk caused by pregnancy.
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. DOI: http://dx.doi.org/10.7554/eLife.00996.001.
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, United States.
authors.forename: Svasti
authors.initials: S
authors.lastname: Haricharan
authors.forename: Jie
authors.initials: J
authors.lastname: Dong
authors.forename: Sarah
authors.initials: S
authors.lastname: Hein
authors.forename: Jay P
authors.initials: JP
authors.lastname: Reddy
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Du
authors.forename: Michael
authors.initials: M
authors.lastname: Toneff
authors.forename: Kimberly
authors.initials: K
authors.lastname: Holloway
authors.forename: Susan G
authors.initials: SG
authors.lastname: Hilsenbeck
authors.forename: Shixia
authors.initials: S
authors.lastname: Huang
authors.forename: Rachel
authors.initials: R
authors.lastname: Atkinson
authors.forename: Wendy
authors.initials: W
authors.lastname: Woodward
authors.forename: Sonali
authors.initials: S
authors.lastname: Jindal
authors.forename: Virginia F
authors.initials: VF
authors.lastname: Borges
authors.forename: Carolina
authors.initials: C
authors.lastname: Gutierrez
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Pepper J
authors.initials: PJ
authors.lastname: Schedin
authors.forename: C Kent
authors.initials: CK
authors.lastname: Osborne
authors.forename: David J
authors.initials: DJ
authors.lastname: Tweardy
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis; D001943:Breast Neoplasms / Q000150:complications / Q000378:metabolism / Q000517:prevention & control*; D063646:Carcinogenesis; D002455:Cell Division; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D009154:Mutation; D009857:Oncogenes; D011247:Pregnancy; D011252:Pregnancy Complications, Neoplastic / Q000378:metabolism / Q000517:prevention & control*; D050799:STAT5 Transcription Factor / Q000378:metabolism
chemical_list: D050799:STAT5 Transcription Factor
keywords: STAT5; breast cancer; chemoprevention; pregnancy