Does IVF increase the risk of breast cancer

Recently, a study was published examining whether there is a link between breast cancer and infertility treatments. The study, published in Fertility and Sterility, a prominent journal that publishes infertility research, looks at all patients in Western Australia who had in vitro fertilization (IVF) between 1983-2002 and then examines how many of those patients developed breast cancer. This type of cohort study is similar in design to the study I wrote about recently that examined the link between birth defects and in vitro fertilization.

Since there is one identification/insurance number for all citizens (ie. Imagine that your social security number was the same as your health care insurance policy number), nations with "single payer" systems can easily link hospital data, cancer registry, and population data allowing researchers to perform these type of epidemiological studies.

There were 21,000 women who had an infertility diagnosis code assigned to their name between 1983-2002. The authors compared women with infertility who had IVF to those women with infertility who did not have IVF. When examining the cancer registry up to 2010, they found, among those 21,000 women, 384 who went on to develop breast cancer.

The authors concluded that there was no risk associated with infertility treatments and the overall risk of breast cancer.

Interestingly, they did find an age related risk linking young age (<24 years) of IVF treatment with breast cancer, but surprisingly did not see that same relationship with older women?

After reviewing this article, several points come to mind:
First, some well known reproductive/hormonal breast cancer risk factors:
1. early age of menarche (age of first period)*
2. late age of menopause*
3. nulliparity (i.e never being pregnant)
4. age of first pregnancy (i.e age >35 with first pregnancy is associated with an increased risk of breast cancer)
5. prolonged, exposure to elevated circulating levels of estrogen^

* These risk factors and others: family, genetic history of breast cancer, smoking, other dietary risk factors, were not included in the study...would this controlling for these confounders change the result? perhaps
^ Not surprisingly the authors provided the peak concentration of estrogen in an IVF cycle (4000 pg/mL) when comparing the estrogen concentration to the peak in a normal menstrual cycle (300 pg/mL).  IVF requires hormones that increase the concentration of circulating estrogen levels, however this is short lived (ie <2 weeks) and the average patient's peak estrogen level is usually 2000-2500 pg/mL. Patients rarely (<1%) achieve estrogen concentrations of 4000 pg/mL in an IVF cycle.

While I am reassured that the overall risk of breast cancer is not elevated in infertile women who undergo IVF compared with infertile women who do not undergo IVF, I don't know how to explain the increased risk of breast cancer among women <24 yrs old who undergo IVF compared to other infertile women  who do not undergo IVF?

Here is a formal response from the American Society of Reproductive Medicine (ASRM):

Linda Giudice, MD, PhD, President-elect of ASRM, noted, “The development of breast cancer is linked to estrogen exposure and the longer one is exposed, the greater the risk.  In an IVF cycle, there is a short, but significant elevation in circulating estrogen, and whether this is linked to the observations found in this study is not clear at this time. Women should be reassured that, overall, IVF was not associated with an increased risk for development of breast cancer.  However, as noted in the study, women in their thirties and forties still need to be aware of the increased risk of breast cancer associated with delivering one’s first child at this stage of reproductive life.  For younger women, there is the possibility that IVF is associated with increased risk, but more research is needed to confirm this.”

There is always extensive counseling between patient and physician in the infertility clinic setting and time is often spent discussing study findings like these. Obviously, this is a new finding that needs to be validated before it can be taken at face value, but patients should be informed. 

Ultimately, whenever I see studies linking infertility treatments to female cancer, I follow this logic: 

If a young women (in the case of this study <24 yrs of age) gets pregnant with IVF she is no longer nulliparous, and has a young first age of pregnancy. She has the opportunity now to breastfeed and a chance to go on and have multiple children - all things which reduce the risk of breast cancer!

I look forward to your comments