Tsubura Airo, Uehara Norihisa, Matsuoka Yoichiro, Yoshizawa Katsuhiko, Yuri Takashi
Department of Pathology II, Kansai Medical University, Moriguchi, Osaka 570-8506, Japan.
In Vivo. 2008 Mar-Apr;22(2):191-201.
Early age at full-term pregnancy lowers the risk of breast cancer in women; lactation seems to be of marginal importance and aborted pregnancy is not associated with reduced risk. Although early full-term pregnancy provides protection against breast cancer, first full-term pregnancy in older women appears to increase the risk. The protective effect of pregnancy has also been observed in rats and mice; in these animals, lactation has an additive effect and interrupted pregnancy provides partial but significant protection. Pregnancy at a young age (< or = 3 months) is highly effective, but pregnancy in older animals (> or = 4 months) is less effective. Parity-induced protection against mammary cancer in rodents can be reproduced by short-term treatment (approximately equivalent to gestational period of rodent or shorter) with the pregnancy hormones, estrogen and progesterone. Administration of pregnancy hormones to nulliparous women may be a useful strategy for protection against breast cancer. However, estrogen and progesterone are thought to play major roles in promotion of the proliferation of breast epithelial cells. Thus, the duration of such treatment and the age at which it is administered are essential factors that require further study. Experimental data suggest that short-term treatment of older rats (aged 6 months) with estrogen and progesterone accelerates mammary carcinogenesis and that long-term (>20 weeks) treatment abolishes the cancer-suppressing effect or even accelerates mammary carcinogenesis. Thus, the available evidence suggests that age and duration of estrogen and progesterone treatment are particularly important factors for protection from breast cancer.
足月妊娠时年龄较小可降低女性患乳腺癌的风险；哺乳似乎重要性不大，而流产与风险降低无关。尽管足月妊娠早期可预防乳腺癌，但老年女性的首次足月妊娠似乎会增加风险。在大鼠和小鼠中也观察到了妊娠的保护作用；在这些动物中，哺乳具有累加效应，而妊娠中断可提供部分但显著的保护。幼年（≤3个月）时妊娠效果极佳，但老年动物（≥4个月）妊娠效果较差。在啮齿动物中，通过用妊娠激素雌激素和孕激素进行短期治疗（约相当于啮齿动物的妊娠期或更短），可重现经产对乳腺癌的保护作用。对未生育女性施用妊娠激素可能是预防乳腺癌的一种有用策略。然而，雌激素和孕激素被认为在促进乳腺上皮细胞增殖中起主要作用。因此，这种治疗的持续时间及其施用年龄是需要进一步研究的关键因素。实验数据表明，对6个月龄的老年大鼠用雌激素和孕激素进行短期治疗会加速乳腺癌变，而长期（>20周）治疗会消除癌症抑制作用，甚至加速乳腺癌变。因此，现有证据表明，雌激素和孕激素治疗的年龄和持续时间是预防乳腺癌的特别重要因素。
