The risk of breast cancer increases in women whose first pregnancies occur after the age of 35. This may be due to a single factor known as STAT5, according to researchers from Baylor College of Medicine (BCM). According to Dr. Yi Li, associate professor in the Lester and Sue Smith Breast Center at BCM and director of the current study, “pregnancy is strongly associated with breast cancer risk, but depending on the age of the woman the effects are in the opposite direction.”
It is known that early first pregnancy protects against breast cancer later in life, while late first pregnancy after the age of 35 increases the risk of breast cancer. The question is, why? This would seem to be contradictory and has perplexed researchers for years. However, new research from Li’s lab may have the answer and at the same time provide a new strategy for breast-cancer prevention.
Hormones during pregnancy and lactation cause growth of the breast at least in part by activating the STAT5 protein. After weaning, the STAT5 protein activity in normal breast cells tends to disappear, and many of the cells undergo apoptosis which had been held in check by STAT5. This remodeling of breast tissue leaves the cells less likely to multiply and thus less likely to acquire cancer-causing mutations. This explains the protective effect of pregnancy in younger women. However, women who are older before their first pregnancy may have already accumulated cancer-causing mutations that allow them to retain active STAT5, thereby escaping programmed cell death and develop into cancer. Researchers were able to confirm this hypothesis in mice.
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Researchers discovered that pre-cancerous lesions often retain their pregnancy-caused STAT5 activation even after weaning and thus continued growing after normal cells had ceased, frequently leading to cancer. Li notes, “You have a persistent survival signal that allows the lesion to expand. With a larger lesion, the risk of breast cancer increases.”
The researchers also discovered that after weaning, a short course of a drug that inhibits STAT5 allowed for normal programmed cell death of these cells and greatly reduced the development of cancer. This suggests that a similar therapy with a STAT5 inhibitor after a women’s late first pregnancy may be able to eliminate the extra risk of cancer. This may help other women at a high risk of breast cancer as well.
There is a current triple negative breast cancer clinical trial underway nationwide to test a new breast cancer treatment. Click the map below for more information:
As a first test, Li and his team are planning a study in women with ductal carcinoma in situ or early premalignant breast lesions that have been scheduled for surgery. These women will be given a STAT5 inhibitor for two weeks. Their breast tissue will be evaluated after surgery to determine if the drug was effective. If this is successful, this may open the door to a larger clinical trial and a new way to breast-cancer prevention.
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