The initial publication by Pike et al.(1983) of the ‘‘breast tissue age’’model for breast cancer incidence, hypothesizing a one-time transient increase in breast 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 [3–9]. 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 longterm protection fully attained within 15 years [2]. But what was the existing evidence in the early 1980s that motivated Pike to postulate his original ‘‘breast tissue age’’model, against the background of the welldocumented observation that parous women have a much lower lifetime breast cancer risk than nulliparous women?[24–26]. A brief conversation with Pike reveals that two specific phenomena as reported in the epidemiological literature contributed to the formulation of his original model. First, several authors observed that the age-specific pattern of breast cancer risk implies a ‘‘crossover’’effect of parity during the childbearing age [27–29]. Specifically, Janerich and Hoff (1982)[28] showed that married women are at a higher risk of breast cancer relative to single women during childbearing years, with a reversal of this pattern at older ages. A second and somewhat ‘‘anomalous’’finding was the observation that, when FFTP occurs at or after 35 year of age, it increases rather than decreases the lifetime risk of the ever-parous women relative to the nulliparous [24, 26, 30]. Pike asked:‘‘Could both of these phenomena be a manifestation of the same underlying biological process?’’The answer is yes. The most commonly postulated biological process for the dual effect of pregnancy on breast cancer risk proposes that the hormonal milieu of pregnancy increases cell proliferation, including the proliferation of the already-initiated cells, yet at the same time inducing terminal differentiation of the mammary gland, rendering it less susceptible to the carcinogen stimuli [31–33]. The results from animal models lend credence to the above hypotheses by …