Introduction

Breast cancer (BC) is the most common cancer in women worldwide. The estimated incidence of BC in the USA, in the year 2003 is approximately 211,300 with 40,200 deaths in women (1). In spite ofbetter screening, earlier diagnosis, and improved therapeutic procedures, there is as yet no cure for metastatic BCs. BC incidence is very high in developed countries and is increasing rapidly in developing countries.

Attempts at prevention of BC are important areas of clinical and experimental investigations, and many different approaches are being used for such studies (2). Currently, there are only three clinical procedures for BC prevention. Women at high risk for BC can opt for risk reduction by bilateral mastectomy and/or oophorectomy, as well as chemoprevention using long-term treatment with the anti-estrogen, Tamoxifen (2). Neither of these procedures is universally acceptable, all have serious side effects, causing physical and psychosocial problems. These are severely anguishing choices for women.

There is a fourth choice for BC prevention in women. It involves undergoing multiple pregnancies along with prolonged nursing beginning at a relatively early age (3). Thus, pregnancy- and nursing-related protection from BC is a universal phenomenon, common to women ofall ethnicities, worldwide. Although pregnancy and nursing are the only natural phenomena with few adverse side effects, it appears unlikely that many of the 21st Century women would choose this option. An acceptable alternative would be to determine the reasons for this protective effect, and to introduce it to nulliparous women, preferably by a short-term, safe, non-invasive procedure. Therefore, this universal protective effect of pregnancy is clearly of major consideration in devising experimental strategies for BC prevention.

Rats and mice (4-9) that undergo a full-term pregnancy also have a greatly reduced susceptibility to chemical carcinogen-induced mammary carcinogenesis (MC) compared to nulliparous rats and mice. Our current research goals are to develop safe, short-term hormonal prevention procedures that will mimic the protective effect of pregnancy against MC in nulliparous rats exposed to potent chemical carcinogens. In order to accomplish this goal, it is absolutely essential to characterize the parous phenotype of women, mice, and rats in relation to their refractoriness to MC. This chapter is divided into two parts. First, we summarize the current status of our knowledge of the parous phenotype in these three species. Second, we will describe studies of our published and unpublished results in attempts to develop a non-invasive, safe, and short-term hormonal treatment in nulliparous rats, mimicking the protective effect of full-term pregnancy. Surprisingly, in nulliparous rats, short-term exposure to high pregnancy levels of mimics the protective effect of pregnancy against mammary cancer (10, 11). Recent comparisons of pregnancy levels of hormones between Chinese and Caucasian women with low and high BC risks, respectively, have observed significantly higher levels of E2 in the low risk Chinese women (18).

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