Lactation on Breast Tumorigenesis

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Epidemiological studies have demonstrated that a first birth before age 25 lowers breast cancer (BCa) risk, while a first birth after age 35 increases BCa risk. This age-dependent impact of first birth on BCa risk is generally attributed to the pregnancy itself, with much less consideration for the lactation that often ensues. In young women, evidence is strong that both pregnancy itself and lactation decrease BCa risk. However, the relative contribution of pregnancy vs. lactation to increased BCa risk associated with a late-age reproduction has not been studied rigorously, either epidemiologically or experimentally. Lactation itself at any age is assumed to be beneficial to both mothers and infants, and is encouraged. However, our preliminary data suggest the hypothesis that lactation instigates preexistent early lesions to progress to cancer. Given the increasingly large population of women who choose to delay their first pregnancy to age 35 or older when the chance of having accumulated early lesions is heightened, our hypothesis, if proven, has important and immediate implications for these women and especially for women have been diagnosed with atypia. They can use this knowledge to make informed decisions regarding whether and how long they will breastfeed. We will test this hypothesis and study the underlying molecular mechanism by pursuing three aims: Specific Aim 1. To further elucidate the impact of pregnancy vs. lactation on breast cancer risk of preexistent mammary early lesions. Specific Aim 2. To investigate how lactation modulates the progression path of precancerous lesions. Specific Aim 3. To further elucidate lactation-induced changes in precancerous lesions.