In vitro fertilization and breast cancer risk: a review

Breast cancer is a classic model of a hormone-dependent malignancy. Since the drugs used for ovulation induction as part of in vitro fertilization (IVF) treatment increase the levels of endogenous gonadal hormones, concerns have arisen regarding a possible association between IVF and the risk of developing breast cancer. The aim of this paper was to review the literature and examine the potential effects of IVF treatment on breast cancer risk.

Medline search was conducted using the key words below in English-language articles. Further papers were obtained using the bibliographies of relevant articles. Furthermore, a combined analysis of retrieved data was performed.

Fifteen studies were identified; of these, 11 were cohort studies and 4 were case-control studies. None of the individual studies showed an overall significant association between IVF and breast cancer and, in fact, one study showed that treatment with hCG significantly reduced the risk of breast cancer in women whose maximum nonpregnant body mass index was less than 27.5. A combined analysis of the cohort studies including a total of 60,050 women treated with ovulation induction/IVF showed no significant association between these treatments and increased risk of breast cancer (observed vs. expected: 601 vs. 568, pooled relative risk [RR] = 1.06, P = 0.337). The case-control studies included a total of 11,303 women in the breast cancer groups and 10,930 controls. Women in the breast cancer groups were slightly less likely to have received IVF (2.2% vs. 2.5%, pooled RR = 0.88, P = 0.231). However, one study showed that infertility treatment was associated with an increased risk of breast cancer of borderline significance among women with a family history of the disease. Another study showed that the incidence of breast cancer within the first year of exposure to fertility drugs was higher than expected, possibly due to the promotion of preexisting cancer lesions caused by superovulation or due to the early diagnosis made in the course of IVF treatment. Conflicting results were reported regarding the type of fertility treatment and breast cancer risk.

Overall, there is no clear evidence that ovulation induction or IVF increases the risk of breast cancer. However, there may be a transient increase in the incidence of breast cancer in the first year due to earlier diagnosis. Furthermore, the risk may be increased in women with a positive family history. Future research should focus on the type of fertility treatment used and breast cancer risk. Aromatase inhibitors should be evaluated further as an alternative to standard ovulation-inducing drugs.