Powell MJ, et al., 2019

Most breast cancers begin in the parts of the breast involved in milk production known as terminal duct lobular units, or TDLUs. These small structures form the milk-producing system of the breast and are especially active during puberty and pregnancy. Over time, and particularly after a woman finishes having children, these structures usually shrink or disappear in a natural process called involution. Women with fewer TDLUs are generally at lower risk of developing breast cancer, because there are fewer places in the breast where cancer can begin.

In addition to natural aging, some life events may speed up this involution process. One of those events is having hypertension (high blood pressure) during pregnancy, a condition known as a hypertensive disorder of pregnancy (HDP). This includes pregnancy complications like gestational hypertension and preeclampsia. Researchers have noticed that women who go through HDP tend to have a slightly lower risk of developing breast cancer later in life.

This may be due to how HDP influences certain hormones and growth signals in the body. For example, women with HDP tend to have lower levels of a hormone called insulin-like growth factor 1 (IGF-1). IGF-1 plays a key role in breast development, and lower levels of it may encourage the breast tissue to go through TDLU shrinkage earlier, potentially reducing cancer risk.

But hormone levels alone may not fully explain this effect. How a woman’s breast tissue responds to these hormonal changes could also depend on her genetics and small differences in the genetic code, called genetic variants, can affect how our bodies work. This study focused on a particular genetic variant in a gene called IGF1R, which helps control how sensitive the body is to the IGF-1 hormone. The specific variant studied is known as rs2016347, and people who inherit the T version of this variant tend to produce less of the IGF1R protein. This could make their breast tissue less responsive to IGF-1 and therefore more likely to undergo TDLU shrinkage.

The researchers wanted to find out whether women who both had HDP and carried this IGF1R variant were more likely to have breast tissue that had undergone involution—meaning fewer TDLUs—and therefore be at lower risk for breast cancer.

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What did they study?

To explore this, the researchers used samples from the Susan G. Komen Tissue Bank. This allowed the team to study normal breast tissue, not tissue affected by disease.

They selected breast tissue samples from 191 white, non-Hispanic women who had given birth. Some of the women had experienced HDP during pregnancy, and others had not. The researchers also looked at each woman’s IGF1R gene to determine whether she had 0, 1, or 2 copies of the T version of the rs2016347 variant.

For each tissue sample, the researchers counted the number of TDLUs present. They then analyzed the data to see if there was a link between HDP, IGF1R genetic variants, and TDLU counts.

What did they find?

1. Among women who had experienced HDP, those with two copies of the T version of the IGF1R variant had 53% fewer TDLUs than those with none. This suggests greater breast tissue involution and potentially a lower risk of developing breast cancer.
2. Within the HDP group, for each copy of the T variant, the number of TDLUs decreased by about 32%. This means the more T variants a woman had, the fewer TDLUs were present in her breast tissue.
3. Among women without HDP, there was no significant connection between the IGF1R variant and TDLU count. The gene variant alone didn’t seem to affect breast involution unless the woman had also experienced HDP. Other known breast cancer risk factors—like age, family history, body weight (BMI), and number of children—were also linked to TDLU counts. For example, older age was linked to fewer TDLUs, and having more children or a family history of breast cancer was linked to more TDLUs.

Why is this study important?

Importantly, this research helps explain why some women with HDP may have a lower breast cancer risk, especially if they also carry the T version of the IGF1R gene variant. It shows that the interaction between our genes and our pregnancy experiences can shape how our bodies age and how diseases may develop—or be prevented—later in life.

Full citation

Powell MJ,Dufault SM,Henry JE,Allison AC,Cora R,Benz CC Pregnancy Hypertension and a Commonly Inherited IGF1R Variant (rs2016347) Reduce Breast Cancer Risk by Enhancing Mammary Gland Involution.. Journal of oncology 2019; 2019. PMID:31687025.