Women who undergo a full-term pregnancy at an early age are less likely to develop
breast cancer than are women who never get pregnant. Scientists experimenting with
rodents now have evidence that a cancer-fighting protein called p53 accounts for
The researchers propose that estrogen and progesterone, produced in abundance
during pregnancy, alter breast cells in some fundamental way that enables them to
produce ample p53 later in life. This girds cells against substances or various
types of energy, such as radiation, that scramble DNA. These genetic
rearrangements can start the cell proliferation that marks cancer.
Other researchers have suggested that pregnancy hormones make a woman’s breasts
more resistant to cancer because they cause breast cells to differentiate into new
structures, including ducts to transport milk. This differentiation decreases the
number of certain breast cells present in so-called terminal end buds, which some
scientists suspect are susceptible to cancer.
Bert W. O’Malley and his colleagues at the Baylor College of Medicine in Houston
conducted pregnancy-simulation experiments in which they gave young female rats
and mice that hadn’t ever been pregnant injections of estrogen and progesterone
over several weeks. Other never-pregnant mice received an inert substance. The
team also studied rodents that had given birth and nursed pups but received no
When subsequently injected with cancer-causing chemicals, animals that had
received hormones or had been pregnant responded by producing more p53 protein in
breast cells than untreated animals did.
Ten days after exposure to a carcinogen, rodents that had received hormones or had
been pregnant showed markedly less cell proliferation in the breast tissues than
did animals that had received inert injections. Most of the study’s results are
slated to appear in the Oct. 23 Proceedings of the National Academy of Sciences.
Besides estrogen and progesterone, prolactin and various other hormones trigger
the differentiation of mammary tissue during pregnancy. But drugs that stimulate
prolactin failed in a past test to protect animals against carcinogens. To see
whether p53 explains the difference, O’Malley and his colleagues induced prolactin
production in some rats and then tested their cells for p53.
Breast cells in these animals showed no more p53 when exposed to carcinogens than
did cells in animals getting a placebo. That suggests that it’s the estrogen and
progesterone in the hormone mix, not the presence of prolactin and its effects,
that spur production of cancer-protective p53, say the researchers.
In other words, “differentiation doesn’t explain the protection you get from
pregnancy-hormone release,” says Geoffrey L. Greene of the University of Chicago.
The p53 molecule switches various genes on and off, and the resulting chain of
events probably brings about a form of suicide in cancer cells, which halts
progression of the disease, says Lewis A. Chodosh of the University of
Pennsylvania in Philadelphia. It may also halt the cell’s normal cycle of growth
and division. This freezing of the cell cycle would enable DNA damaged by
carcinogens to be repaired by the cell’s built-in maintenance machinery, Chodosh
The p53 protein isn’t abundant in normal tissues. This study suggests that
estrogen and progesterone released in pregnancy “activate a long-lasting p53
switch,” says D. Joseph Jerry of the University of Massachusetts in Amherst. Still
unclear is how the hormones perform this feat, says Jerry.