Postpartum Involution and Cancer: An Opportunity for Targeted Breast Cancer Prevention and Treatments?
Postpartum Involution and Cancer: An Opportunity for Targeted Breast Cancer Prevention and Treatments?
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DOI：
10.1158/0008-5472.can-19-3448
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发表时间：
2020-05-01
期刊：
影响因子：
11.2
通讯作者：
Schedin P
中科院分区：
文献类型：
--
作者：
Borges VF;Lyons TR;Germain D;Schedin P
任何年龄的分娩都会在产后的第一个十年中短暂地增加患乳腺癌的风险，而这种不良反应的窗口期在晚产妇女中延长了20年（约35岁）。怀孕的保护作用取决于第一次怀孕的年龄，年轻母亲受益最大。此外，产后5 - 10年期间的乳腺癌诊断与随后的转移性疾病的高风险相关。值得注意的是，哺乳已被证明对乳腺癌发病率具有总体保护作用，其保护程度因种族、多胎和哺乳的终生持续时间而异。哺乳期对乳腺癌诊断后预后的影响尚未见报道。我们讨论了这些流行病学发现的最新数据和机制见解。在妊娠结束后5-10年内确诊的妇女中，产后乳房复旧已被确定为转移风险增加的关键中介。在乳房复发期间，免疫回避、淋巴网络增加、细胞外基质重塑和肝脏和淋巴结播种增加作为相互关联的途径，导致产后诊断的不利影响。我们还讨论了母乳喂养保护作用的新机制。总的来说，这些机制的见解为预防和/或改善产后乳腺癌的治疗提供了潜在的治疗途径。
Childbirth at any age confers a transient increased risk for breast cancer in the first decade postpartum and this window of adverse-effect extends over two decades in women with late age first childbirth (>35 yoa). Cross-over to the protective effect of pregnancy is dependent on age at first pregnancy, with young mothers receiving the most benefit. Further, breast cancer diagnosis during the five-ten-year postpartum window associates with high risk for subsequent metastatic disease. Notably, lactation has been shown to be protective against breast cancer incidence overall with varying degrees of protection by race, multiparity and lifetime duration of lactation. An effect for lactation on breast cancer outcome after diagnosis has not been described. We discuss the most recent data and mechanistic insights underlying these epidemiologic findings. Post-partum involution of the breast has been identified as a key mediator of the increased risk for metastasis in women diagnosed within 5–10 years of a completed pregnancy. During breast involution, immune avoidance, increased lymphatic network, extracellular matrix remodeling and increased seeding to the liver and lymph node work as interconnected pathways, leading to the adverse effect of a postpartum diagnosis. We also discuss a novel mechanism underlying the protective effect of breastfeeding. Collectively, these mechanistic insights offer potential therapeutic avenues for the prevention and/or improved treatment of postpartum breast cancer.