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10.1245/s10434-007-9800-2
Annals of Surgical Oncology 15:1048-1055 (2008)
© 2008 Society of Surgical Oncology
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Original Article

The Possible Association between IVF and Breast Cancer Incidence

I. Pappo, MD1,2, L. Lerner-Geva, MD PhD3, A. Halevy, MD2, L. Olmer, MSc4, S. Friedler, MD5, A. Raziel, MD5, M. Schachter, MD5 and R. Ron-El, MD5

1 Comprehensive Breast Care Institute, Assaf Harofeh Medical Center, affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Israel, Zerifin, 70300, Israel
2 Division of Surgery, Assaf Harofeh Medical Center, affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Israel, Zerifin, 70300, Israel
3 Women and Children’s Health Research Unit, Gertner Institute for Epidemiology and Health Policy Research, Tel Hashomer, affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Tel Hashomer, Israel
4 Biostatistics Unit, Gertner Institute for Epidemiology and Health Policy Research, affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Israel, Tel Hashomer, Israel
5 IVF and Infertility Unit, Assaf Harofeh Medical Center, affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Israel, Zerifin, 70300, Israel

Correspondence: Address correspondence and reprint requests to: I. Pappo, MD; E-mail: pappo{at}zahav.net.il

Background: The possible association between ovulation-inducing drugs and breast cancer development has been debated. Our aim was to evaluate the incidence of breast cancer in a cohort of women exposed to in vitro fertilization (IVF).

Methods: A retrospective cohort analysis was performed by linkage of the computerized database of all women treated at the IVF Unit at Assaf Harofeh Medical Center between 1986 and 2003, and the Israeli National Cancer Registry. The standardized incidence ratio (SIR) was computed as the ratio between the observed number of breast cancer cases and the expected cases, adjusted for age and continent of birth, in the general population. Tumor characteristics of the IVF patients were studied by reviewing original medical records.

Results: 35 breast carcinomas were diagnosed among 3,375 IVF-treated women, compared to 24.8 cases expected (SIR = 1.4; 95% CI 0.98–1.96). Age ≥40 years at IVF treatment (SIR = 1.9; 95% CI 0.97–3.30), hormonal infertility (SIR = 3.1; 95% CI 0.99–7.22), and ≥4 IVF cycles (SIR = 2.0; 95% CI 1.15–3.27) were found to be risk factors to develop breast cancer compared to the general population. Multivariate analysis revealed that women who underwent ≥4 IVF cycles compared to those with one to three cycles were at risk to develop breast cancer, although not significantly (SIR = 1.9; 95% CI 0.95–3.81). Of IVF-treated women 85% had ER(+) tumors and 29% had positive family history.

Conclusions: A possible association between IVF therapy and breast cancer development was demonstrated, especially in women ≥40 years of age. These preliminary findings need to be replicated in other cohort studies.

Key Words: Breast cancer • In-vitro fertilization • Ovulation induction






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