Breast cancer risk after ovarian stimulation for In vitro fertilization

The study by Dr van den Belt-Dusebout and colleagues1 investigated a debated aspect of reproductive medicine: breast cancer risk following ovarian stimulation for in vitro fertilization (IVF).2-5 The authors concluded that “these findings are consistent with absence of a significant increase in long-term risk of breast cancer among IVF-treated women”.1 However, some important points should be discussed. For about 23 % of women, sub-fertility diagnosis and number of IVF cycles were collected using a questionnaire since medical records were not available. This high rate threatens the reliability of results. It is not possible to compare a detailed report of official medical records with data deriving from subjective memory of treatments received many years before. This may be a strong bias, because reproductive medicine, IVF strategies and the pharmacological protocols have changed rapidly in the last decades. Dates of diagnosis and histology were reported but unfortunately not disease staging. It would be interesting to investigate if ovarian stimulation with the use of IVF techniques can promote the occurrence of biologically different types of breast cancer, as in the case of tamoxifen-related endometrial cancer, a neoplasia with better prognostic profile and outcome. Also, the authors reported that breast cancer risk decreased with more IVF cycles (7 or more compared with 1-2). They suggested as potential explanations that women treated with more IVF cycles received more hCG or had longer periods of down-regulation with low estradiol and progesterone levels, or the women requiring more IVF cycles were inherently different. It is difficult to provide a definitive conclusion since the clinical outcomes of IVF cycles were not reported. The decreased risk in women treated with many IVF cycles also could be related to the improvement of ovarian function after repeated endocrine stimulations. Infertility and infertility-related nulliparity must be considered as risk factors for breast cancer, and prolonged treatment of anovulatory or poor ovulatory cycles could be one approach for restoring normal ovarian activity and reducing breast cancer risk.