The role of age at first and at second birth on subsequent breast cancer risk was analyzed using pooled data from 2 hospital-based case-control studies conducted in Italy, for a total of 1,200 biparous cases and 987 controls. Compared with women who gave birth for the first time below age 20, the relative risks were above unity for those with later first birth, even after allowance for age at second birth, although the trend was inconsistent across subsequent strata. A similar direct trend in risk was observed in relation to age at second birth: compared with less than 25 years and after allowance for age at first birth, the point estimates were 1.2, 1.4 and 1.4 for 25-29, 30-34 and greater than or equal to 35 (p for linear trend = 0.04). The results for age at first and at second birth were similar in the 2 studies pooled in this analysis. A significant interaction with age was observed in relation to age at first and at second birth. In younger women (below age 50) a strong and direct association with age at first birth was found, while no apparent protection was conveyed by earlier second birth. Among older women (aged 50 or over), there was no apparent relationship with age at first birth after allowance for age at second, but the role of age at second birth was independent and statistically significant. Thus, our study confirms an independent and significant role of age at second birth in biparous women, after allowance for age at first birth, and indicates that, after reciprocal allowance, the role of first and second birth was not apparently different. The relative risks for both variables were quantitatively moderate, and may be influenced by age or other temporal variables.
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