Author response: Mechanism and preclinical prevention of increased breast cancer risk caused by pregnancy
Year: 2013
Type: peer-review
Abstract: Pregnancy changes the probability that a woman will later develop breast cancer. If a woman’s first pregnancy occurs before her 22nd birthday, the chances of developing breast cancer are reduced. However, if the first pregnancy occurs after her 35th birthday, there is an increased risk of breast cancer. It is not clear why this age-related difference exists, but as more women wait until their 30s to start a family, there is greater urgency to understand this difference. Breasts undergo extensive changes during pregnancy. This remodeling makes their cells less likely to multiply, and also less likely to develop tumors, which could explain the protective effect of pregnancy for younger women. But why would older women not reap the same benefits? One hypothesis is that older first-time mothers are more likely than younger first-time mothers to already have breast tissue with cells carrying cancer-causing mutations, or to have clusters of abnormal precancerous cells. Now, Haricharan et al. have tested this hypothesis by inserting two cancer-causing genes into female mice. Half of the mice were then made pregnant and allowed to nurse their young, whilst the other half were never mated. Although, both groups of mice later developed tumors, the mice that had been pregnant developed more tumors and did so faster. The increased cancer levels in the mice that had been pregnant were not due to them having more precancerous cells at the early stages of pregnancy than the unmated mice of the same age. Further, the precancerous cells in the impregnated mice did not proliferate faster than those in the mice that were never pregnant. Instead, pregnancy weakened the protective process that culls pre-existing precancerous cells. These cells evaded destruction by activating a signaling pathway called the STAT5 pathway in response to pregnancy hormones. Haricharan et al. also examined tissue samples from women with a very early form of breast cancer and found elevated levels of STAT5 in tumors from women who had been pregnant compared to those who had not been pregnant. The good news is that precancerous cells do not always become cancerous. However, for those women with a high risk of developing breast cancer, Haricharan et al. suggest that temporarily reducing STAT5 activity after pregnancy with medication might reduce this risk. Treating mice with anti-STAT5 drugs for a few weeks after they finished nursing their young lessened the elevated cancer risk, and so the next challenge is to see if this approach will also be effective in human clinical trials.
Language: English
Topic: Cancer Risks and Factors
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W2989072326