文章：

妊娠相关乳腺癌及其转移

Pregnancy-associated breast cancer and metastasis

原文发布日期：2006-04-01

DOI: 10.1038/nrc1839

类型: Review Article

开放获取: 否

要点：

1. The protective effect of pregnancy is neither immediate nor constant — a transient increase in breast cancer risk occurs with pregnancy in women of all ages. The risk of pregnancy-associated breast cancer is greatest in older first-time mothers.
2. Pregnancy-associated breast cancer has a higher mortality rate because metastasis is common. Possible reasons for breast cancer metastasis with pregnancy include the promotional effects of pregnancy-associated hormones and a delay in diagnosis in recently-pregnant women. However, existing data indicate that these factors do not account for the high mortality associated with pregnancy-associated breast cancer.
3. Following pregnancy and lactation, the mammary gland regresses to its pre-pregnant state by a tissue remodelling process known as involution. The microenvironment of the involuting mammary gland shares attributes with inflammation and wound healing.
4. Because pro-inflammatory tissue environments can promote tumorigenesis, the involuting mammary gland might be tumorigenic. Candidate mediators of tumour cell progression during gland involution include an influx of activated immune cells, increased concentrations of matrix metalloproteinases, remodelling of mammary extracellular matrix with subsequent release of tumour-promoting growth factors and matrix fragments with bioactivity, and loss of basement-membrane barrier function.
5. Under normal conditions of involution, pro-inflammatory pathways are activated, but the balance of pro- to anti-inflammatory signals is tipped towards suppression of overt inflammation.
6. The presence of occult disease at the time of gland involution is anticipated to aggravate the tumour-promoting microenvironment by tipping the balance towards overt inflammation. So, women with occult disease at the time of pregnancy might be at an increased risk of tumour cell dissemination during mammary gland involution.
7. As the average age of child-bearing continues to rise, the incidence of pregnancy-associated breast cancer and its associated high mortality rate are also anticipated to rise.

要点翻译：

1. 妊娠的保护作用既非即时也非恒定——各年龄段女性在妊娠期间均会出现乳腺癌风险的短暂增加。妊娠相关乳腺癌风险在首次生育的高龄母亲中最为显著。
2. 妊娠相关乳腺癌死亡率较高，因其常发生转移。妊娠合并乳腺癌转移的可能原因包括妊娠相关激素的促进作用以及近期妊娠女性诊断延迟。然而现有数据表明，这些因素并不能完全解释妊娠相关乳腺癌的高死亡率。
3. 妊娠和哺乳结束后，乳腺组织通过称为"复旧"的组织重塑过程恢复至孕前状态。复旧期乳腺的微环境具有炎症和伤口愈合的特征。
4. 由于促炎性组织环境可促进肿瘤发生，复旧期乳腺可能具有致瘤性。腺体复旧期间肿瘤细胞进展的潜在介质包括：活化免疫细胞的浸润、基质金属蛋白酶浓度的增加、乳腺细胞外基质重塑伴随释放具有生物活性的促瘤生长因子和基质片段，以及基底膜屏障功能的丧失。
5. 在正常复旧条件下，促炎通路虽被激活，但促炎与抗炎信号的平衡倾向于抑制显性炎症。
6. 若腺体复旧时存在隐匿性疾病，预计将通过打破平衡倾向显性炎症而加剧促瘤微环境。因此，妊娠时存在隐匿性疾病的女性在乳腺复旧期间可能面临肿瘤细胞扩散的风险增加。
7. 随着平均生育年龄持续上升，妊娠相关乳腺癌的发病率及其相关高死亡率预计也将随之增加。

英文摘要：

Pregnancy-associated breast cancer, which has a poor prognosis, is often overlooked by clinicians and researchers alike. With the trend towards delayed child-bearing, an increase in the occurrence of breast cancer complicated by pregnancy is anticipated. The mechanisms that have been proposed to account for this poor prognosis, including increased hormone exposure, might not contribute significantly to the observed increase in metastasis seen in these patients. Instead, the mammary microenvironment might become tumour-promoting after pregnancy because of the remodelling of the mammary gland to its pre-pregnant state. This remodelling, which is associated with pro-inflammatory and wound-healing mechanisms, is proposed to support tumour-cell dissemination. This hypothesis will be discussed.

摘要翻译： 

妊娠相关乳腺癌预后不良，却常被临床医生和研究者忽视。随着生育年龄推迟，预计乳腺癌合并妊娠的病例将增加。目前认为预后差的原因包括激素暴露增加，但这可能并非患者转移率升高的主要因素。相反，乳腺微环境在妊娠后可能因腺体向孕前状态重塑而促瘤；这种伴随促炎与创伤愈合机制的重塑，被认为有助于肿瘤细胞播散。本文将探讨这一假说。

原文链接：

Pregnancy-associated breast cancer and metastasis