Fertility drugs used to stimulate ovulation did not increase the chances of breast cancer for most women in a long-term study of around 10,000 women in the USA.
However, an elevated risk was noted in women who were treated with high doses that are no longer recommended and a subset of women who did not become pregnant after treatment.
As previous studies have produced mixed results on the effect of fertility treatment on breast cancer risk, lead study author Dr Louise Brinton of the National Cancer Institute, USA, said her team set out to look at any long-term effect 'after controlling for other factors that have been shown to be correlated with both breast cancer risk and use of those drugs'.
She added: 'Overall, our data show that use of fertility drugs does not increase breast cancer risk in this population of women, which is reassuring'.
The study looked at women who were evaluated or treated at five clinics in the USA between 1965 and 1988. Just under half received fertility treatment with clomifene citrate and/or gonadotrophins. All patients were followed up over the course of 30 years and breast cancer rates were compared between groups. The researchers took into account confounding factors like a family history of breast cancer.
Most women who received clomifene citrate did not show an increased risk of breast cancer compared with women not given fertility drugs. However, those who received 12 or more cycles of this drug were one-and-a-half times more likely to develop invasive breast cancer.
Breast cancer risk was also doubled in women who failed to become pregnant following treatment with both clomifene citrate and gonadotrophins. This finding counters that from a separate, smaller study published two years ago, which found a reduced breast cancer risk for women given fertility drugs who did not become pregnant (see BioNews 666).Dr Brinton remarked: 'The observed increase in risk for these small subsets of women may be related to persistent infertility rather than an effect of the medications. Nevertheless, these findings stress the importance of continued monitoring of women who are exposed to fertility drugs'.
Current recommendations in the USA suggest clomifene citrate should be prescribed for a maximum of three to six cycles, with doses of up to 100mg. But when the patients in this study received their treatment the guideline doses were higher, with several women receiving doses of up to 250mg for several years.
Although the increases in breast cancer risk in this population were relatively modest, those who went on to develop breast cancer did so at an average age of 53 years, younger than that seen in the general population.
As well as suggesting that this group of women should continue to be monitored, the authors say that further work is needed to investigate the effect of current fertility drug regimes on breast cancer risk.
The study was published in the journal Cancer Epidemiology, Biomarkers and Prevention.