2011 SABCS, San Antonio Breast Cancer Symposium, 6-10 December, San Antonio, USA

Links between early life exposures and breast cancer

Professor Michele Forman – University of Texas, Austin, USA

I’m presenting data on early life exposures and risk of breast cancer; one part of my data relates to the relationships of a condition called pre-eclampsia. It’s a condition in 5% of women across the world when they’re pregnant, it’s also a condition that is associated with a lower risk of breast cancer. Indeed, women who have pre-eclampsia have as much as a 70% reduction in risk of breast cancer compared to women who do not. The daughters of that pregnancy also have about a 10-60% reduction in risk of breast cancer.

So we began a study in Norway trying to understand why is pre-eclampsia associated with reduced risk of breast cancer. We followed a cohort of women who had been diagnosed with pre-eclampsia in pregnancy and then we identified two sets of women and their offspring as controls, one woman was matched on maternal age to the woman who had pre-eclampsia, because it’s a risk factor, the other women had a match on the gender and the birth date of the offspring of the pre-eclamptic pregnancy. We’ve been following them in utero through adolescence now and some of the data that I’ll be presenting today on the girls only, so we have both girls and boys but I’m only presenting on the girls, relates to a delay in breast development amongst the girls who were daughters of the pre-eclamptic pregnancy at 12-13 years of age, a significant delay in breast development, one that has not been seen before. We think this is an indication that there is a possible reason why pre-eclampsia is associated with a reduced risk of breast cancer. I present some data on hormones, some data on growth on these girls etc.

What are the implications?

We want to understand why pre-eclampsia is associated with a lower risk of breast cancer. We also want to understand what the possible mechanisms are and that’s where things get a little bit tricky because we are doing a human study, we are not doing an animal study so we can’t really investigate the underlying mechanisms to the extent that you can do animal research. With that in mind, we are trying to identify whether there is something called programming that occurs to the mother, because she’s also at reduced risk of breast cancer, as well as her offspring. What comprises that programming, we’re not sure.

Is the potential for a therapy that recreates some of the same effects?

That is the potential that we’re hoping for, pre-eclampsia is not a condition women would want to have in pregnancy and we don’t want anyone having that but we do want to appreciate and understand the association with the lower risk, the protection from breast cancer.

One other study where we looked at early life exposures and age at menarche of the daughter and we looked at the maternal lifestyle in pregnancy and we found that the mother who was very physically active in pregnancy, compared to the mother who was not, has a daughter who delays menarche by three months on average. That may not seem like a lot of a difference but three months translates to about 40 years over time, so we do think that that’s a considerable finding that we have.

Then we also looked at the role of weight gain in pregnancy on the risk of early menarche in the daughter, and early menarche would be defined as a girl who reaches menarche before she reaches 11 years of age. What we found was that the women who have a very low weight gain, which is about less than 10lbs, or women who have an extremely high weight gain of 40lbs or more, actually have daughters who are at increased risk for early menarche. Why this is so we’re looking into as well.