In Vitro Fertilization Is Not Associated with an Increased Risk of Breast Cancer in Women

EBM Focus - Volume 11, Issue 30

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Reference - JAMA 2016 Jul 19;316(3):300 (level 2 [mid-level] evidence)

  • Hormone exposure has been shown to influence women’s risk of breast cancer; however, it is unclear if hormone exposure during in vitro fertilization (IVF) increases this risk.
  • A recent study in the Netherlands comparing women receiving IVF to women having other fertility treatments over 20 years of follow-up found that IVF is not associated with an increased risk of breast cancer and individual aspects of fertility treatment did not appear to influence breast cancer risk.
  • Longer follow-up is needed to determine whether IVF is associated with an increased risk in postmenopausal women.

Many factors contribute to a woman’s risk of breast cancer, including her reproductive history and hormonal exposure (J Natl Compr Canc Netw 2015 Jul;13(7):880). IVF significantly alters hormone exposure and as such could influence breast cancer risk. To determine the long-term influence of IVF on breast cancer risk, a recent cohort study included 25,108 women (mean age at baseline 33 years) who received fertility treatments between 1980 and 1995 in the Netherlands and were followed for a median of 21.1 years. Within this cohort, 19,158 women (76%) had IVF for a mean of 3.6 cycles and 5,950 women received other fertility treatments. Most women in the IVF group had regimens consisting of gonadotropin stimulation with follicle stimulating hormone or human menopausal gonadotropin with gonadotropin releasing hormone. Conversely, women in the non-IVF group received tubal surgery, intrauterine insemination with low-dose ovarian stimulation, hormonal treatments such as clomiphene, or withdrew from the waiting list for IVF.

Over the entire follow-up period, 839 cases of first invasive breast cancer and 190 cases of ductal carcinoma in situ (DCIS) were reported. The incidence of breast cancer in the general Dutch population during the same time period was calculated from the Netherlands Cancer Registry as an additional control. The rate of breast cancer per 100,000 women was 163.5 in the IVF group, 167.2 in the non-IVF fertility treatment group, and 163.3 in the general population (no significant differences across groups or in any pairwise comparisons). Additional analyses found that in women having IVF, there was a decreased risk of breast cancer with ≥ 7 IVF cycles compared to 1-2 IVF cycles (adjusted hazard ratio [HR] 0.55, 95% CI 0.39-0.77), and with poor response at first IVF cycle compared to normal response (adjusted hazard ratio 0.77, 95% CI 0.61-0.96). Breast cancer risk was higher in women who were older at conception, as well as in parous compared to nulliparous women (adjusted hazard ratio 1.35, 95% CI 1.16-1.56). Other aspects of fertility treatment including subfertility diagnosis, number of IVF cycles, number of IVF and intrauterine insemination cycles, number of ampules used for stimulation during IVF, number of oocytes collected, and type of luteal phase support did not appear to influence the risk of breast cancer in women having infertility treatments. There were no significant differences comparing IVF to other infertility treatments in subgroup analyses.

While several studies have investigated the potential impact of IVF treatment on the incidence of breast cancer, the results have largely been inconsistent; studies often are unable to control for infertility or have short follow-up durations (Hum Reprod Update 2014 Jan-Feb;20(1):106). This cohort study overcomes these challenges by including women with infertility receiving treatment other than IVF to better control for population-based risk factors. Additionally, the median follow-up was over 20 years and only 25% of women were< 50 years old at the time of analysis. Although the long follow-up duration adds to the evidence suggesting IVF does not increase the risk of breast cancer, it may also limit the generalizability of these results. IVF treatment has changed in the last 20 years, and differences in hormone exposure will need to be further assessed. Also, while the age-related increase in the risk of breast cancer is consistent with previous studies, the finding that nulliparity was associated with an increased risk of breast cancer is at odds with other epidemiological data (J Natl Compr Canc Netw 2015 Jul;13(7):880). It is unknown if this discrepancy is intrinsic to women receiving infertility treatment, or if other factors, including the short duration of postmenopausal follow-up, may explain this difference. Overall, these results suggest that IVF treatment may not increase breast cancer in premenopausal women. Continued follow-up including additional postmenopausal data is needed to determine if these results persist in postmenopausal years.

For more information see the Risk factors for breast cancer and Treatment of infertility in women topics in DynaMed Plus. DynaMed users click here and here.