Full-term pregnancy has long been associated with a reduced risk of breast cancer, but a new study finds women who give birth multiple times actually increase their risk of “triple-negative” breast cancer, a relatively uncommon but particularly aggressive subtype of the disease.
“Triple-negative” breast cancer, while rare, has a poorer prognosis than other types of breast cancer and doesn’t respond to hormone-blocking therapies such as tamoxifen.
And, conversely, women who have never given birth have a 40 percent lower risk of developing the specific type of breast cancer than women who have given birth multiple times.
“Unlike most breast cancers, triple-negative tumors don’t depend on hormonal exposures to grow and spread, so our assumption going into the study was that reproductive factors would not be associated with a woman’s risk of this cancer subtype,” said Amanda Phipps, Ph.D., lead study author and postdoctoral research associate in the Public Health Sciences Division of Fred Hutchinson Cancer Research Center.
“We were surprised by these findings because researchers have known for quite some time that women who have children, especially those who have them at an early age and have multiple full-term pregnancies, have a lower risk of breast cancer overall.”
No fear
These findings should not scare women into never having children, however.
While never giving birth appears to be protective against triple-negative breast cancer, the researchers found women who remain childless have about a 40 percent higher risk of estrogen-receptor-positive breast cancer -- the most common form of the disease, which can be treated with estrogen-blocking drugs -- as compared to those who have one or more offspring.
This higher risk of estrogen-receptor-positive breast cancer among women who have not had children is well established, and it is thought to be related to the fact that such women do not undergo pregnancy-related changes in the breast that confer a lifelong protective effect.
Phipps said the mechanisms by which full-term pregnancy contributes to an increased risk of triple-negative breast cancer and a decreased risk of other forms of the disease are not clear.
“We do know that the hormones of pregnancy induce certain changes in the cellular structure of the breast. Overall, those changes seem to make the breast less susceptible to cancer. It is possible, however, that the increased risk of triple-negative breast cancer we found in women who had given birth may be due to some abnormal response of their breast tissue to the hormones of pregnancy,” said Phipps.
Phipps said another possibility is that pregnancy somehow makes the breast more susceptible to certain carcinogens even while reducing breast cancer risk overall.
For the study, which was based on data from the Women’s Health Initiative, Phipps and colleagues analyzed the detailed reproductive histories of some 150,000 postmenopausal women, more than 300 of whom went on to develop triple-negative breast cancer.
“This particular study is significant because it is one of the largest studies ever conducted on the impact of reproductive history on triple-negative breast cancer,” said Phipps.
Not just one disease
Triple-negative breast cancer, which refers to any breast cancer that does not express the genes for estrogen receptor (ER), progesterone receptor (PR) or Her2/neu, accounts for only 10 percent to 20 percent of all breast cancers, and only in the past decade have researchers become aware that this cancer subtype exists.
Phipps said this research reinforces the notion that breast cancer is not just one disease.
“The mechanisms that lead to triple-negative breast cancer are likely different from those that lead to other forms of the disease. We still have a lot to learn about what causes this more aggressive form of breast cancer, but we hope that research like this will help us develop better tools to identify those women at greatest risk.”
It is known that this cancer subtype is more predominant in African American women and it tends to be diagnosed at an earlier age.
Researchers also know there is a strong link between genetic mutations in the so-called “breast cancer gene,” BRCA1, and triple-negative breast cancer.
“More research is needed to better understand the causes of the most aggressive and lethal forms of breast cancer. While this study adds to our knowledge base, it should not change women’s approaches to breast cancer screening,” said Phipps.
These findings are published online ahead of the March 16 issue of the Journal of the National Cancer Institute.
