Fertility Drugs' Link to Breast Cancer Hinges on Pregnancy, Study Says

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Do fertility drugs affect a woman's risk of developing breast cancer? A new study suggests that the risk hinges on whether they actually help a woman get pregnant.

Scientists have been concerned about the effects of fertility drugs in recent years, citing a possible relationship between the hormones altered by the drugs and those implicated in breast cancer. Studies attempting to pinpoint the link between fertility drugs and cancer risk have varied widely in their conclusions. Some have found a reduction in cancer risk, some an increased risk. Others found no connection at all.

But researchers at the National Institutes of Health found that although the drugs seem to reduce breast cancer risk in young women, the risk goes up when they get pregnant.

Researchers studied pairs of sisters, in total following more than 1,400 women who had been diagnosed with breast cancer before age 50 and more than 1,600 of their sisters who had never had breast cancer. Of these women, 288 reported using ovulation-stimulating fertility drugs, clomiphene citrate and follicle-stimulating hormone, at some point; 141 women reported a pregnancy lasting 10 weeks or more after taking the drugs.

The study found that women who took the drugs and did not get pregnant had a slightly lower risk of developing breast cancer before age 50. Those who took the drugs and reported a pregnancy lasting 10 weeks or more had a slightly increased risk, but that risk was little different than the risk of women who never took fertility drugs at all.

The study was published today in the Journal of the National Cancer Institute and funded in part by Susan G. Komen for the Cure.

Clarice Weinberg, one of the study's authors and the head of biostatistics at the National Institute of Environmental Health Sciences, said those findings suggest that a stimulated pregnancy may be enough to undo the reduction in risk possibly conferred by ovulation-stimulating drugs. But she does not suggest that women should steer clear of fertility drugs for fear of developing breast cancer.

"I don't see the results as any cause for alarm. But everyone needs to manage their risk and be careful," she said.

Dr. Marcelle Cedars, a professor of reproductive endocrinology at the University of California, San Francisco, said the findings are actually encouraging to women who want to take fertility drugs.

"Even in the group at an increased risk after their pregnancy, their risk was not higher than the general public," said Cedars, who was not involved in the study. "If you use fertility drugs, you're not increasing your risk."

The study looked specifically at ovulation-stimulating drugs, which kick a woman's ovaries into hyper-ovulation, causing her body to produce more eggs that could potentially be fertilized. The additional eggs also increase the levels of estrogen in a woman's body, a hormone that has been linked to an increased risk of breast cancer.

In women who have higher levels of eggs and hormones but no pregnancy, the hormone levels eventually fall back down when the woman's body figures out she's not pregnant. But in women who do get pregnant, the multiple eggs keep producing hormones. Weinberg and her colleagues suggest that those higher hormone levels may act on breast tissue that naturally changes during the course of pregnancy.

But Louise Brinton, chief of hormonal reproductive epidemiology at NCI, cited another possible explanation for the findings. Most of the women taking fertility drugs were taking clomiphene, a first-line treatment for infertility. Clomiphene is in the same drug family as the chemotherapy agent tamoxifen, which might explain why some women taking it appeared to have a reduced risk of breast cancer.

Also, pregnant women, especially those who are age 30 and older, are at an increased risk of breast cancer for a few years after they give birth, whether or not they have taken fertility drugs.

"You would expect to see that women with recent pregnancies would be at increased risk," said Brinton, who was not invovled in NIH study. "Then you start to see that risk turn into lifetime protection relative to women who have never had a pregnancy."

Weinberg said future research on fertility drugs and breast cancer should consider the role that pregnancy plays in affecting younger women's risk for developing the disease.

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