Unsuccessful fertility treatment reduces young-onset breast cancer risk

By Sarah Guy

Women who are treated unsuccessfully with fertility drugs have a significantly reduced risk for developing young-onset (under 50 years) breast cancer, compared with nonusers of such drugs, show the results of a sister-matched case-control study.

However, the association was only significant in women who had not conceived a pregnancy lasting 10 weeks or longer after treatment, report the researchers from the National Institute of Environmental Health Sciences in North Carolina, USA.

Conversely, women who had used fertility drugs and conceived a pregnancy lasting 10 weeks or longer had a significant almost twofold increased risk for breast cancer compared with unsuccessfully treated women.

"For those who achieve conception through treatment, the elevated production of ovarian hormones early in a stimulated pregnancy might increase the risk of breast cancer by modifying pregnancy-related remodeling of breast tissue," write Clarice Weinberg and colleagues in the Journal of the National Cancer Institute.

The team explains that breast cancer in women younger than 50 years is rare, but that it can be aggressive and carry a worse prognosis than breast cancers diagnosed in older women.

Using data from the Two Sister Study involving women aged 35-74 years who were asked about their history of fertility treatment, the researchers assessed the effects of fertility drugs clomiphene citrate (CC) and follicle-stimulating hormone (FSH) in 1422 women diagnosed with breast cancer under the age of 50 years, and their 1669 breast cancer-free sisters (controls).

Analysis showed that the 193 women who used CC alone or CC plus FSH (n=66) had a nonsignificant reduced risk for young-onset breast cancer compared with nonusers, and after adjustment for nonexposure to a pregnancy lasting at least 10 weeks, this association became significant. Specifically, unsuccessful users of CC were 39% less likely than nonusers to develop the disease, and users of CC and FSH were 47% less likely.

The researchers report that the number of FSH-only users in the study sample was small, and they showed a nonsignificant reduction in cancer risk.

The same trends were observed when the researchers stratified the women by exposure to any drug or drug combination, versus nonexposure.

"Our data suggest that exposure to a stimulated pregnancy is enough to undo the reduction in risk associated with a history of exposure to ovulation-stimulating drugs," concludes the team.

In an accompanying editorial, Louise Brinton, from the National Cancer Institute in Rockville, Maryland, remarked that several biologic explanations are possible for the observations of Weinberg et al.

"Reduced risks are possible given that clomiphene is a selective estrogen receptor modulator with structural similarities to tamoxifen, a well-established chemopreventive agent for breast cancer," she explained.

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