Lactation on Breast Tumorigenesis

流行病学研究表明，25岁之前生育第一胎可降低乳腺癌（BCa）风险，而25岁之前生育第一胎可降低乳腺癌（BCa）风险。 35岁以后的第一次生育会增加BCa风险。第一胎对BCa风险的这种年龄依赖性影响通常是 由于怀孕本身，少得多的考虑往往伴随着哺乳。在年轻女性中， 有充分的证据表明，怀孕本身和哺乳都会降低BCa风险。然而，相对贡献 尚未研究妊娠与哺乳对与晚期生殖相关的BCa风险增加的影响 无论是流行病学上还是实验上。任何年龄的哺乳本身都被认为是有益的 母亲和婴儿，并鼓励。然而，我们的初步数据表明， 促使先前存在的早期病变进展为癌症。鉴于越来越多的妇女， 选择将第一次怀孕推迟到35岁或35岁以上，因为早期病变累积的可能性很小。 如果我们的假设得到证实，对这些妇女有重要而直接的影响， 被诊断出患有乳腺癌的女性他们可以利用这些知识做出明智的决定， 他们是否会母乳喂养，以及母乳喂养的时间。我们将测试这一假设，并研究潜在的分子 具体目标有三个：一是具体目标。为了进一步阐明妊娠与哺乳对 乳腺癌的风险既存乳腺早期病变。具体目标2。研究哺乳如何调节 癌前病变的进展路径。具体目标3。为了进一步阐明哺乳诱导的 癌前病变

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.