Modern reproductive patterns associated with estrogen receptor positive but not negative breast cancer susceptibility

C Athena Aktipis¹, Bruce J Ellis², Katherine K Nishimura², Robert A Hiatt²

Affiliations

¹ 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 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.
² 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.

PMID: 25389105
PMCID: PMC4362290
DOI: 10.1093/emph/eou028

Modern reproductive patterns associated with estrogen receptor positive but not negative breast cancer susceptibility

C Athena Aktipis et al. Evol Med Public Health. 2014.

. 2014 Nov 10;2015(1):52-74.

doi: 10.1093/emph/eou028.

Authors

C Athena Aktipis¹, Bruce J Ellis², Katherine K Nishimura², Robert A Hiatt²

Affiliations

¹ 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 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.
² 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.

PMID: 25389105
PMCID: PMC4362290
DOI: 10.1093/emph/eou028

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.

Keywords: age of first birth; breast cancer heterogeneity; cancer evolution; evolutionary mismatch; hormone-associated breast cancer; parity.

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Figures

**Figure 1.**
(a) Parity is associated with a lower risk of ER-positive breast cancer. (b) Parity is not associated with risk of ER-negative breast cancer. OR was calculated using a random effects model to account for heterogeneity of study populations. The red squares and horizontal black lines represent the ORs and 95% CIs for each study. The black diamond and its width represent the overall effect estimate and the 95% CI. The vertical black line represents the null hypothesis (OR of 1). Premeno. = pre-menopausal, Postmeno. = post-menopausal, ER = estrogen receptor, PR = progesterone receptor, TN = triple negative, HER2 = human epidermal growth factor receptor 2, Lum. = luminal

**Figure 2.**
(a) Later age of first birth is associated with a higher risk of ER-positive breast cancer. (b) Later age of first birth is not associated with risk of ER-negative breast cancer. OR was calculated using a random effects model to account for heterogeneity of study populations. The red squares and horizontal black lines represent the ORs and 95% CIs for each study. The black diamond and its width represent the overall effect estimate and the 95% CI. The vertical black line represents the null hypothesis (OR of 1). Premeno. = pre-menopausal, Postmeno. = post-menopausal, cont. = continuous, ER = estrogen receptor, PR = progesterone receptor, TN = triple negative, HER2 = human epidermal growth factor receptor 2, Lum. = luminal, LE = less than or equal to, GE = greater than or equal to

**Figure 3.**
(a) Early age of menarche is associated with a higher risk of ER-positive breast cancer. (b) Early age of menarche is also significantly associated with risk of ER-negative breast cancer, though the effect is not as strong as for ER-positive breast cancer. OR was calculated using a random effects model to account for heterogeneity of study populations. The red squares and horizontal black lines represent the ORs and 95% CIs for each study. The black diamond and its width represent the overall effect estimate and the 95% CI. The vertical black line represents the null hypothesis (OR of 1). Premeno. = pre-menopausal, Postmeno. = post-menopausal, cont. = continuous, ER = estrogen receptor, PR = progesterone receptor, TN = triple negative, HER2 = human epidermal growth factor receptor 2, Lum. = Luminal, LE = less than or equal to, GE = greater than or equal to

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Modern reproductive patterns associated with estrogen receptor positive but not negative breast cancer susceptibility

Affiliations

Modern reproductive patterns associated with estrogen receptor positive but not negative breast cancer susceptibility

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