Pregnancy and Mammary Tumors in Rats


In humans, pregnancy protects against spontaneous mammary tumors later in life

In humans, the incidence of breast cancer is significantly reduced in women who have had a full-term pregnancy early in life (Russo and Russo, 1997, Russo et al.2005). MacMahon et al. (1970) found that women who experience a full-term pregnancy before age 20 have half the risk of developing breast cancer compared to women who never have a full-term pregnancy.

Pregnancy protects against chemically-induced mammary tumors

Many studies have examined the protective role of pregnancy and pregnancy hormones on the incidence of chemically-induced mammary tumors in rats. Rats who go through a full-term pregnancy are less likely to develop mammary cancer in response to carcinogens than unmated rats. Sinha et al. (1988) found that 70% of unmated rats developed chemically-induced mammary tumors, compared to 14% of rats that experienced full-term pregnancy. Swanson and Christov (2003) found that 100% of unmated rats exposed to a carcinogen developed multiple mammary tumors each, whereas the rats that went through full-term pregnancy developed an average of 0.4 cancers per rat.


Pregnancy hormones protect against chemically-induced mammary tumors

The protective effect of pregnancy on the incidence of mammary tumors can be induced with hormones that mimic those found during pregnancy. Unmated female rats who are given human chorionic gonadotropin (hCG) (Russo and Russo, 2000), or estradiol and progesterone (Blakely et al. 2006, Guzman et al. 1999, Medina 2004, Rajkumar et al. 2004, Swanson and Christov 2003) develop significantly fewer tumors in response to a carcinogen than rats that were exposed to the carcinogen but were not given pregnancy hormones. Pregnancy hormones inhibit the initiation and progression of chemically induced mammary carcinomas. Three weeks of exposure to low doses of estrogen and progesterone produces the same protective effect against chemically-induced tumors as pregnancy (Medina 2004).


How does pregnancy protect against mammary tumors?

Pregnancy exposes the mammary gland to high levels of ovarian, pituitary, and placental hormones. These hormones prepare the mammary tissue to produce milk. These changes alter nature of the mammary tissue such that it becomes permanently less likely to develop tumors (Russo and Russo 1996). The exact mechanism is not fully understood. Pregnancy may cause cells in mammary tissues to become less responsive to carcinogens, or may cause them to proliferate less, or the hormonal environment may be different, or there may be a change in cell fate. For a discussion of various hypotheses, see Sivaraman and Medina, 2002. Also see Blakely et al. 2006, Russo et al. 2006, Russo and Russo 1997, Uehara et al.2006, Schedin et al. 2004 for more detail on the possible mechanism involved.


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