Dual effect of first full term pregnancy on breast cancer risk: empirical evidence and postulated underlying biology.

Abstract

cancer risk due to first full-term pregnancy (FFTP) with subsequent lifetime reduction in risk due to parity, has been followed by many empirical confirmations of these hypotheses including the current article [1, 2]. The "breast tissue age" model implies that, for a certain time period after FFTP, ever-parous women are at a higher risk for breast cancer relative to nulliparous women [39]. Subsequent extensions of this model incorporated transient increases in risk due to each full-term pregnancy (FTP), effects of age at first and last FTP, duration between adjacent pregnancies, time since last delivery, as well as other risk factors that influence the prediction of breast cancer incidence [3, 10-23]. These models have been tested and evaluated by large epidemiological studies in varied ethnic populations. Although the results differ somewhat for specific populations and modeling approaches, the overall observations can be summarized as follows: FFTP is the most important determinant of the dual effect of pregnancy with subsequent FTPs exerting similar yet quantitatively much less important short-term increases followed by long-term decreases in breast cancer risk. Moreover, the degree to which the short-term increase and the longterm protection of parity are observed in a given population is determined by the distribution of ages at first and subsequent pregnancies as well as total parity within that population. The lower the age at FFTP and subsequent FTPs, and the shorter the intervals between adjacent pregnancies, the greater the long-term protection. This protection is universally observed among women of various ethnic and racial groups. In the current article, comparison of uniparous with nulliparous women shows that short-term increase in breast cancer risk (OR = 1.49 (95% CI 1.01-2.20)) peaks in the window of around five years post-FFTP, with the long