Life history theory and breast cancer risk: methodological and theoretical challenges

In a meta-analysis published by myself and co-authors, we report differences in the life history risk factors for estrogen receptor negative (ER-) and estrogen receptor positive (ER+) breast cancers. Our meta-analysis did not find the association of ER- breast cancer risk with fast life history characteristics that Hidaka and Boddy suggest in their response to our article. There are a number of possible explanations for the differences between their conclusions and the conclusions we drew from our meta-analysis, including limitations of our meta-analysis and methodological challenges in measuring and categorizing estrogen receptor status. These challenges, along with the association of ER+ breast cancer with slow life history characteristics, may make it challenging to find a clear signal of ER- breast cancer with fast life history characteristics, even if that relationship does exist. The contradictory results regarding breast cancer risk and life history characteristics illustrate a more general challenge in evolutionary medicine: often different sub-theories in evolutionary biology make contradictory predictions about disease risk. In this case, life history models predict that breast cancer risk should increase with faster life history characteristics, while the evolutionary mismatch hypothesis predicts that breast cancer risk should increase with delayed reproduction. Whether life history tradeoffs contribute to ER- breast cancer is still an open question, but current models and several lines of evidence suggest that it is a possibility.