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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Dec 31, 2013
- Source ID
- 10.7554/elife.00996
Entities
People
- C. Kent Osborne
- Carolina Gutierrez
- David J Tweardy
- Hong Zhang
- Jay P. Reddy
- Jie Dong
- Kimberly Holloway
- Michael Toneff
- Pepper J Schedin
- Rachel Atkinson
- Sarah Hein
- Shixia Huang
- Sonali Jindal
- Susan Hilsenbeck
- Svasti Haricharan
- Virginia F Borges
- Wendy Woodward
- Yi Li
- Zhijun Du
Organizations
- Baylor College of Medicine
- Cancer Prevention and Research Institute of Texas
- Congressionally Directed Medical Research Programs
- Dan L. Duncan Cancer Center, Baylor College of Medicine
- Nancy Owens Memorial Foundation
- National Institutes of Health
- Robert and Janice McNair Foundation
- The University of Texas MD Anderson Cancer Center
- University of Colorado Denver