Abstract: Two recently published studies from American Cancer Society grantees Traci R. Lyons, PhD, and Ceshi Chen, PhD, highlight some of the risks of cancer associated with pregnancy, and help untangle the threads between normal and cancerous cells.
One of the reasons that cancer is so difficult to treat is that it often occurs by hijacking normal biology to cause disease. Pregnancy at a younger age is associated with a reduced risk of breast cancer during a woman’s life. Although the total risk is reduced over several decades, a more careful analysis reveals that there is a temporary increase in risk for breast cancer immediately following pregnancy. Society grantee Traci Lyons, PhD, working in the laboratory of former grantee, Pepper Schedin, PhD, at the University of Colorado, has discovered a biological mechanism that may account for a major portion of this short-term increase in breast cancer risk in postpartum women (Nature Medicine, August 2011).
Following pregnancy and the cessation of milk production by the breast, the milk sacs normally break
down to be replaced by fat tissue. During this process, two genes – collagen and the enzyme, COX2 –
are turned on at high levels.
In this study, Lyons shows that, in mice, both collagen and COX2 work together to promote normal breast tissue remodeling following lactation. But when the process is hijacked by a cancerous cell, they collaborate to promote breast cancer growth.
We already knew that increases in collagen are associated with growth and metastasis of breast cancer. In addition, we knew that the enzyme COX2 is strongly associated with risk of colon cancer, prompting great interest in the use of a common class of drugs called nonsteroidal anti-inflammatory drugs (NSAIDs), which inhibit the COX enzymes, in colon cancer prevention. Aspirin, ibuprofen, and naproxen are all NSAIDs.
This new study suggests the possibility that postpartum breast cancer could be prevented with something as simple as ibuprofen. Of course, the question remains whether it is both safe and effective in humans, and this study lays the groundwork for answering that question.
Another recent publication, by American Cancer Society grantee Ceshi Chen, PhD, from the University of Rochester, has identified a critical target of progesterone in the breast, which has important implications for breast cancer (Molecular Endocrinology, July 2011). In recent years, we have learned that when progesterone was included in hormone replacement therapy for older women there was an increase in the risk of breast cancer. Progesterone is important during pregnancy to stimulate the development of milk glands.
Chen has found that in both normal and cancerous breast cells, progesterone induces a transcription
factor, KLF6, which turns on a collection of genes important for growth of the milk ducts. Unfortunately, in a breast cancer cell, when KLF6 is turned on by progesterone, it promotes tumor growth.
A detailed understanding of how progesterone stimulates both normal and cancer cell growth will provide the basis for future prevention and treatment strategies – strategies that can interfere with the activities of progesterone and KLF6 in breast cancer cells, without disrupting their normal activities important for pregnant women.