TABLE D-8 Comparison of Risk Factors for Mammary Cancer in Mice, Rats, Dogs, and Humans

Risk Factor

Mice

Rats

Dogs

Humans

Increasing age

Higher age at first pregnancy

?

?

?

Ever pregnant

?

?

Oophorectomy

?

?

Obesity

? = not studied; ↑ = increased; ↓ = decreased.

estrogen in humans might affect mammary tumors through their effect on a novel pituitary mammary mitogen.

INTERESTING QUESTIONS RAISED BY ANIMAL STUDIES

A comparison of information about mammary cancer in mice, rats, beagles, and humans (Table D-8) shows that our knowledge of risk factors for mammary cancer in mice and rats is very poor. It would be easier to judge how much one could extrapolate between these two species and humans if there was as much information about spontaneous mammary cancer in these animals as there was for humans.

Consideration of both the epidemiology of mammary cancer in animals, including humans, and the material presented here raises some interesting questions. Does pregnancy alter the risk of mammary cancer in rats and mice? If so, does it do so by altering prolactin levels, suggesting that prolactin is a unifying mechanism for mammary cancer in mice and rats? Similarly, are increasing rates of mammary cancer with age in free-living beagle dogs accompanied by increasing levels of growth hormone? Are endogenous levels of prolactin predictive of mammary cancer in rats and mice, and are endogenous levels of growth hormone predictive of mammary cancer in beagles? Do estrogens, progestogens, and estrogen/progestogen combinations affect prolactin levels and growth hormone levels in humans? Last, if progestogens importantly modify the effect of estrogen on mammary carcinogenesis of sex steroid in mice, rats, and dogs, is it possible that the secular changes in the balance of estrogen and progestogen in commonly used oral contraceptives in different places explain differences in some of the risk estimates that have been derived from these studies?

Better integration of information from animal studies of mammary cancer and steroid contraceptives with thinking about human epidemiological data would undoubtedly advance our understanding of



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