IVF treatment is not associated with an increased long-term risk of breast cancer

When women undergo IVF (in vitro fertilization) treatment they will have to boost their body with extra hormones such as estrogen and progesteron, hormones that have been implicated in a higher breast cancer risk. Strict regulation resulting in increased as well as decreased levels of these and other hormones during an IVF cycle is required in order for the woman to stimulate her ovaries to produce as many (good quality) eggs as possible and then to create a receptive uterine environment for the future fertilized embryos to attach and grow. Due to the elevated levels (5-10 times the normal) of sex hormones during IVF treatment, there have been raised concerns that this could lead to an increased risk for these women to develop breast cancer.

images-4Recently however, a large study published in JAMA showed that women who underwent IVF treatment were not more likely to be diagnosed with breast cancer compared to the general population. Furthermore, the study examined women who underwent different types of infertility treatments, not only IVF treatments and it showed that there was no increased breast cancer risk in the IVF treated women compared to women who were treated for infertility without undergoing IVF. This comparison is important since women who suffer from infertility may be more prone to certain cancers due to the hormonal imbalances which may cause the infertility in the first place. Therefore this study is considered a more accurate way of assessing the potential impact on IVF treatments and cancer risk than studies where women undergoing IVF have simply been compared to the general population.

This  study was performed in the Netherlands where 25,000 women were followed for a median period of 21 years. 19,000 began IVF treatment (1983-1995) and 6,000 underwent other infertility treatments (1980-1995). The median age of follow-up was 54 for the IVF group and 55 for the other group. Moreover, the researchers took into account different factors linked to higher risk of cancer, including the number of IVF cycles each women underwent, her overall number of births and her age at the time of the birth of her first child.

The researchers found 839 cases of invasive breast cancer and 109 cases of in situ breast cancer in the >25,000 women involved in the study. The risk did not differ by type of fertility drugs. They concluded that the breast cancer risk for the IVF-treated women was not significantly different from the group who underwent other fertility treatments, nor from the general population at 20 years or more after treatment.

Surprisingly, it was shown that women who underwent seven or more cycles of IVF had a lower risk of developing cancer than women who underwent one to two cycles. Furthermore, breast cancer risk was significantly lower for women who responded poorly to ovarian stimulation in their first IVF cycle.

Side-Effects-of-Fertility-Drugs-for-Women-780x519This study confirms the results from two different studies both published in 2013: the first by Brinton et al where it was shown that IVF treatment did not increase the risk of developing breast and endometrial cancers, and the other, a meta-analysis of eight smaller studies, that showed that IVF treatment did not increase breast cancer risk overall. In another study by Brinton et al published in 2014 9,892 women were followed for 30 years after their infertility treatment where they were exposed to the fertility drug clomiphene and  gonadotropins (fertility medication containing follicle-stimulating hormone FSH, alone or in combination with luteinizing hormone, LH). Here, women who were exposed to either type of fertility drug were no more likely to develop breast cancer than those who did not use these drugs to stimulate ovulation. However an increased breast cancer risk was found in a small subset of women who were exposed to the highest doses of clomiphene (12 or more cycles of clomiphene treatment). In 2011, a reduction of both breast and cervical cancer risks was reported in women who underwent IVF treatment compared to women who did not undergo any fertility treatment, over a 8-year follow-up.

However, in spite of the positive results from these studies, one should not forget that the relationship between fertility treatments and increased cancer risk is complex and therefore difficult to investigate. Opposite results have been reported in previous studies, where it was shown that IVF treatment was linked to an elevated risk of developing breast cancer, and that it was linked to age. In 2008, researchers found a potential increase in breast cancer in women >40 years of age who underwent IVF treatment. This was a retrospective analysis of medical records and the researchers called the results “preliminary“. The same year another small study in Israel reported that women who started IVF treatment at the age of of >30 had an increased risk of developing breast cancer. In 2012 however, an Australian study with 21,000 participants showed that IVF treatment was associated with a higher risk to breast cancer only in younger women (24 years or younger) whereas no such link was found in women in their 30s or 40s.

artThese different studies with such variation in outcome, show that the question whether IVF treatment could be associated with an increased breast cancer risk is extremely complex and that we need more studies in order to solve the puzzle. Preferably large studies with a long-term follow up, similar to the recent Dutch study. Wendy Chen, a breast cancer specialist at Dana-Farber Cancer Institute says that “The ideal study would look at how long and in what doses women take fertility drugs, and whether those who took the highest doses for the longest period had the greatest rise in cancer occurrence. But that kind of data has not been consistently collected.” She also mentions that the vast majority of the studies where a connection between fertility treatments and a higher risk of cancer (mainly breast and ovarian) have been investigated, no such connection has been found. The exception are a few smaller studies (like the ones mentioned above), but here she claims that the methods used in these studies have been called into question by some researchers.

So far the results from most studies are encouraging and hopefully researchers will continue to investigate if and how there might be any connection(s) between fertility treatments and an increased cancer risk. In the Netherlands, additional 10,000 Dutch women who have undergone IVF treatment and 5,000 women who received other fertility treatments have already been recruited for a follow-up study.

 

The pictures are borrowed from:

http://www.saferadiotherapy.com/beneficial-bacteria-may-protect-breasts-cancer

http://onfertility.com/side-effects-of-fertility-drugs-for-women

http://www.medscape.com/resource/infertility

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