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Updated: Apr 21, 2026

Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer
Published on: March 17, 2016
Modern reproductive patterns associated with estrogen receptor positive but not negative breast cancer susceptibility
C Athena Aktipis1, Bruce J Ellis2, Katherine K Nishimura2
1Center for Evolution and Cancer, University of California San Francisco, 2340 Sutter Street S-341, Box 0128, San Francisco, CA 94143-0128, USA; Department of Psychology, Arizona State University, PO Box 871104, Tempe, AZ 85287-1104, USA; Norton School of Family and Consumer Sciences, University of Arizona, 650 N Park Ave, Tucson, AZ 85721, USA; Department of Epidemiology and Biostatistics, University of California San Francisco, Box 0560, UCSF, San Francisco, CA 94143, USA Center for Evolution and Cancer, University of California San Francisco, 2340 Sutter Street S-341, Box 0128, San Francisco, CA 94143-0128, USA; Department of Psychology, Arizona State University, PO Box 871104, Tempe, AZ 85287-1104, USA; Norton School of Family and Consumer Sciences, University of Arizona, 650 N Park Ave, Tucson, AZ 85721, USA; Department of Epidemiology and Biostatistics, University of California San Francisco, Box 0560, UCSF, San Francisco, CA 94143, USA aktipis@asu.edu.
Abstract:
It has long been accepted that modern reproductive patterns are likely contributors to breast cancer susceptibility because of their influence on hormones such as estrogen and the importance of these hormones in breast cancer. We conducted a meta-analysis to assess whether this 'evolutionary mismatch hypothesis' can explain susceptibility to both estrogen receptor positive (ER-positive) and estrogen receptor negative (ER-negative) cancer. Our meta-analysis includes a total of 33 studies and examines parity, age of first birth and age of menarche broken down by estrogen receptor status. We found that modern reproductive patterns are more closely linked to ER-positive than ER-negative breast cancer. Thus, the evolutionary mismatch hypothesis for breast cancer can account for ER-positive breast cancer susceptibility but not ER-negative breast cancer.
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