Reassuring Data on IVF and Long-term Breast Cancer Risk

By Megan Brooks

July 20, 2016

NEW YORK (Reuters Health) - Ovarian stimulation for in vitro fertilization (IVF) does not raise the risk of breast cancer, according to a Dutch study.

In a cohort of more than 25,000 women who were followed for more than 20 years after fertility treatments, breast cancer risk in IVF-treated women was not markedly different from that in the general population or in women who underwent other fertility treatments, according to the July 19 JAMA report.

"These results are reassuring for doctors and women treated with IVF in the past indeed, because of the strengths of the study, especially adjustment for confounding and long complete follow-up, and because of the consistency of the results," first author Dr. Alexandra W. van den Belt-Dusebout, Department of Epidemiology, Netherlands Cancer Institute, Amsterdam, told Reuters Health by email.

"The risk did not increase with larger numbers of IVF cycles or with longer follow-up," she added. "We did not identify possible subgroups at increased risk. The risk did not differ by type of fertility drugs or subfertility diagnosis."

IVF procedures might influence breast cancer risk by causing temporary changes in estradiol and progesterone levels. Yet prior studies of breast cancer risk after IVF treatment have been inconclusive.

"This analysis adds to the literature especially because earlier studies, even reviews and a meta-analysis, had methodological limitations, especially relatively short follow-up and relatively small numbers of breast cancers, missing detailed information on IVF treatments or comparison with the general population only," Dr. van den Belt-Dusebout explained.

"Furthermore, earlier results were conflicting, some studies reported no increase of breast cancer, whereas others reported increased risks in subgroups of IVF treated women. Therefore, a large study with long follow-up was needed. The results of this long-term cohort study lacked these earlier methodological limitations," she said.

Among 25,108 women in the cohort, 19,158 started IVF treatment between 1983 and 1995 (IVF group, average number of IVF cycles 3.6) and 5,950 started other fertility treatments between 1980 and 1995 (non-IVF group).

The mean age at entry was 33; the median age at end of follow-up was 54 in the IVF group and 55 in the non-IVF group.

After a median follow up of 21 years, 839 cases of invasive breast cancer and 109 cases of in situ breast cancer were documented in the Netherlands Cancer Registry. The risk of breast cancer in the IVF group was similar to that of the general population (standardized incidence ratio 1.01) and the non-IVF group (hazard ratio 1.01).

The cumulative incidences of breast cancer at age 55 were 3.0% in the IVF group and 2.9% for the non-IVF group (p=0.85) and the risk did not increase with longer time since treatment or number of IVF cycles.

"These findings are consistent with the absence of a significant increase in the long-term risk of breast cancer among women treated with these IVF regimens," the authors write in JAMA.

"This nationwide study is unique because it includes a large number of IVF-treated women and women having undergone other fertility treatments, who have been followed for more than 20 years, with detailed treatment information," Dr. van den Belt-Dusebout told Reuters Health.

"Furthermore, near complete information was obtained on cancer incidence and regarding the most important confounding factors, parity and age at first birth," she continued. "Moreover, the risk of breast cancer among IVF-treated women is compared with the risk among women from the general population and among women having undergone other fertility treatments."

"Although the results are based on women treated in the Netherlands starting their IVF treatments between 1983 and 1995, we believe the results are also applicable for women in other Western countries, because IVF regimens were similar in different countries in similar periods," she noted.

"Because many women in our cohort did not yet reach menopause, it remains important to follow-up the women in the OMEGA cohort to evaluate the risk of postmenopausal breast cancer after IVF. Furthermore, for more recently treated women we cannot be sure yet, because different IVF protocols have been used. However, it is not very likely that more recently treated women would have an increased risk of breast cancer, because these protocols do more resemble women's natural menstrual cycle," Dr. van den Belt-Dusebout said.

"In more recent protocols," she explained, "the down regulation phase is shorter and the stimulation is milder with lower doses of hormones than in the earlier periods. But, to be sure, we need to evaluate their breast cancer risk in a comparable study. We have already collected data from women treated between 1995 and 2001. We will analyze those data in the near future, also with regard to other hormone-related cancers such as ovarian tumors and endometrial cancer."

The study had no commercial funding and the authors have no relevant disclosures related to this work.


JAMA 2016.