A breast cancer connection
Researcher shows link between growth hormones and tumors
Many women over the age of 40 have small tumors in their breasts — usually without even knowing it. Those tumors typically grow to about 1 millimeter in size but then stop developing because they have insufficient nourishment.
How and why do other tumors keep growing into cancer? This question drives the work of biomedical sciences researcher Salman Hyder.
In the Oct. 15 issue of Cancer Research, Hyder and colleagues published findings about progesterone, a hormone common in birth control and treatments for menopause. Their research shows that progesterone actively promotes the progression of human breast cancer cells in an animal model. Previously such observations had been limited to animal cells.
Understanding the processes behind tumor growth is crucial, especially considering that breast cancer is the second leading cause of death for women in the United States. Each year, approximately 40,000 American women die of this disease and doctors diagnose 200,000 new cases, according to figures from the American Cancer Society.
“If we could control these processes, we could potentially control tumor growth and metastasis and thereby alleviate much suffering and save many lives,” Hyder says.
Any new tissue growth requires the formation of new blood vessels — a process called angiogenesis.
Tumor cells can generate signals, in the form of “growth factors,” that allow them to recruit new blood vessels from neighboring tissues. Hyder studies the mechanisms by which these signals generate, specifically focusing on vascular endothelial growth factor (VEGF).
Hyder — the Thelma P. Zalk Missouri Professor of Tumor Angiogenesis and an investigator at Dalton Cardiovascular Research Center — works with colleague Yayun Liang and other collaborators at Mizzou and the University of Texas Southwestern. The group has shown how progesterone and VEGF interact in certain tumor cells with a mutant form of a protein known as p53.
Hyder says that p53 actually suppresses tumors in normal cases. However, some women have a mutant form of p53 that doesn’t work the same way. In these women, progesterone “induces” VEGF elaboration. In more basic terms, this means progesterone can trigger an increase in new blood vessels, which in turn feed a tumor’s development.
Hormone therapies and the dilemma
Salman Hyder and colleagues have shown a link between progesterone and the progression of breast cancer in human cells. Photo by Shane Epping.
Women receive progesterone in birth control and other clinical situations. Synthetic progesterone, or progestin, is given in combination with estrogen as hormone replacement therapy (HRT) to reduce hot flashes, depression and other symptoms of menopause. In HRT, progestin actually prevents the tumors that can develop when estrogen stimulates the uterus.
However, many clinical trials, including the Million Women Study and an extensive National Institutes of Health study known as the Women’s Health Initiative (WHI), show that if taken for a prolonged period, progestin increases the risk of breast cancer by approximately 26 percent.
Therefore, menopausal women find themselves in a dilemma — undergo an HRT regimen with progestin and increase the risk of breast cancer, or seek alternative hormone therapy without progestin and face the risk of developing uterine cancer.
Hyder says this dilemma has given rise to extensive debate. He advises women to consult with their doctors and make an informed decision about whether to take HRT. Physicians can evaluate family history, lifestyle and other factors.
“There is little doubt now that progestins have the capacity to increase the formation of new blood vessels, which in turn can lead to tumor development,” Hyder says. “If there is a propensity for breast cancer in the family, it may well be advisable for a woman to avoid drug regimens containing progestins.”
New discovery and future treatments
Showing a connection between progesterone and breast cancer in human cells is a definitive step, and it leads to further research.
Hyder and his colleagues are studying ways to eradicate tumors by suppressing VEGF and selectively killing the blood vessels that nourish developing tumors. Natural, non-mutant p53 acts as a tumor suppressor and either corrects mistakes or destroys potentially cancerous cells when they go awry.
Such agents would have applications not only in the treatment of breast tumors but also in other forms of cancer. Hyder and colleagues discussed these possibilities in Cancer Research.
“If we can find safe anti-hormones or anti-angiogenic compounds, then we can potentially prevent or arrest tumor growth,” Hyder says.