Pregnancy, fertility treatment, and cancer.

Health and medicine explained.
April 9 2007 2:01 PM

The Lurking Elizabeth Edwards Question

Do pregnancy and fertility treatment increase the risk of breast cancer?

Elizabeth Edwards. Click image to expand.
Elizabeth Edwards

Elizabeth Edwards, wife of presidential candidate John Edwards, re-ignited a national conversation about cancer when she announced in late March that her breast cancer had returned and spread. Mrs. Edwards was first diagnosed with cancer in 2004, when her younger children, Emma Claire and Jack, were 6 and 4 years old. Edwards gave birth to them at ages 48 and 50 after undergoing fertility treatments (the details of which have not been made public).

Amanda Schaffer Amanda Schaffer

Amanda Schaffer is a science and medical columnist for Slate.

No one can say for sure whether these treatments contributed to Edwards' cancer. But the return of her illness has stoked a creeping fear in women who wonder whether monkeying with hormones, getting pregnant, and giving birth late in life may raise the chances of getting breast cancer. Can it? Pregnancy itself is associated with a small, short-term increase in cancer risk, and this may be greater for women who give birth at an older age. But there is little or no evidence that fertility treatments raise the odds of getting the disease. In other words, don't panic.

Here's the research. For a time, women who have recently given birth are more likely to develop breast cancer than peers the same age who have not. At least three large-scale studies—of Norwegian, Swedish, and Danish women—suggest this. The Swedish study, which appeared in the New England Journal of Medicine in 1994, compared women who'd had one child with those who'd never given birth. For up to 15 years following delivery, the childbearing women were slightly more likely to be diagnosed with cancer than their nonchildbearing peers. Age does seem to be relevant: The increased risk was largest in women who were 35 or older when they gave birth. How much higher? Those women's probability of developing the disease by age 40 was 26 percent greater than that of childless peers. (Click here to put that risk in perspective.)

It's important to note that over the long term, childbearing seems to protect against breast cancer. In the Swedish study, women who give birth saw their chances of getting cancer eventually dip below those of their childless counterparts. But other research does not find this protective effect for women who first give birth at 35 or older. In data from the Nurses' Health Study, a large prospective study of risk factors and major diseases in American women, women in the older age group continue to face a higher risk than women without kids do—in other words, the risk added by pregnancy doesn't disappear with time for them. Breast-feeding for an extended time may afford a small amount of additional protection for all women, no matter their ages.

How to explain this jumble of findings? Levels of hormones, including estrogen, shoot sky-high during pregnancy. If precancerous cells exist, the hormones may fuel their growth. (On the other hand, for women who had breast cancer, were successfully treated, and then got pregnant, there's little evidence of a higher risk of the cancer recurring, according to Dr. Nadine Tung, director of the Cancer Risk and Prevention Program at Beth Israel Deaconess Medical Center in Boston.) Older women may be at particular risk of the pregnancy-hormone effect because their breast cells may be more prone to damage from the stimulation that higher hormonal levels cause. After pregnancy, however, cells in the breast differentiate and generally seem to become less susceptible to cancer development. We don't know why this may not hold true for the breast tissue of women whose first pregnancies occur later in life, Tung says.

As for the role of fertility treatments, since some tumors are fueled by estrogen, treatments that boost estrogen levels in theory could further boost the pregnancy-related cancer risk. Such treatments include in vitro fertilization, which in stimulating the ovaries causes estrogen-producing follicles to develop (each containing an egg). This causes levels of the hormone to rise in the bloodstream and reach breast tissue. The increase in estrogen associated with in vitro fertilization is substantial but very brief and poses minimal cancer risk, says Dr. Roger Gosden, a reproductive-medicine expert at Cornell University's Weill Medical College. While comparisons are difficult, he notes, the exposure to hormones from in vitro differs importantly from that of hormone-replacement therapy, which involves a continuous low dose and which turned out to be a bad idea for many women, as new evidence confirmed last week.

The epidemiological data on women who've undergone fertility treatments support Gosden's optimism. One study of Australian women, which appeared in the Lancet in 1999, found that women who'd been exposed to fertility drugs for in vitro were more likely to be diagnosed with breast cancer in the year following treatment. The uptick may have occurred partly because the women were under the watchful eye of reproductive-health experts more likely to detect abnormalities. Or it might have reflected the short-term risk of pregnancy itself. But crucially, when longer-term data were included, the in vitro group appeared no more likely to get breast cancer than women in the general population.

Happily, other papers do not find a link between fertility treatments and breast cancer risk. A 2004 French study, which followed women prospectively, found that with one likely chance exception, "treatment for infertility does not influence breast cancer risk overall." And a 2005 review paper, which scrutinized the safety of fertility drugs, concluded that to date, there has been "no evidence" to demonstrate "a direct association, let alone a causal relationship" between fertility drugs and cancer. All told, at least half a dozen studies dispel the worry that fertility treatments cause a significant increase in breast cancer risk.

Women sometimes go to great lengths to have children—witness writer Peggy Orenstein's recent tales of injecting herself with Italian nuns' urine and downing dubious herbal concoctions. The risks of pregnancy include a slightly higher chance of breast cancer for a time, and for women over 35, the higher odds may endure. Every woman has to decide for herself how to think about these risks. But they probably won't—and shouldn't—stand in the way of most women who want to have children.

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