Dec. 14, 1999 (New York) -- Some types of non-cancerous breast lesions that typically are not associated with increased risk of breast cancer could be more dangerous than doctors previously thought. But a new study in the Dec. 15 issue of the Journal of the National Cancer Institute finds that there may be a way to predict which lesions have cancer potential and possibly give those women drugs that can prevent the cancer from ever occurring.
Non-cancerous or benign breast lesions are common, but are generally not thought to put women at high risk for cancer. One type of benign breast disease considered to have the lowest potential for increasing cancer risk is known as epithelial hyperplastic lesions lacking atypia, or EHLA. Researchers at Vanderbilt University School of Medicine in Nashville studied nearly 10,000 women with EHLA over a 30-year period and found that in those who eventually developed cancer, a receptor known as TGF-beta-R II, whose job it is to 'hear' signals instructing cells not to divide, had lost its ability to 'hear' those signals, resulting in the uncontrolled cell growth characteristic of cancer.
"TGF-beta has been intensively studied for over 10 years now," study author William Dupont, PhD, tells WebMD. "It's known to be a very powerful regulator of cell proliferation."
The researchers suspected that women with fewer of these receptors that still had the ability to 'hear' signals would be more likely to have breast abnormalities progress to breast cancer. Women in the study who had expression of the receptor in fewer than 25% of their breast cells from biopsy had more than three times the risk of subsequent breast cancer compared to women who had expression of the receptor in more than 75% of their cells.
According to Dupont and colleagues, reduction in the amount of the receptor appears to be an early event in the progression from benign breast disease to cancer, but this association remains to be proven.
If the significance of TGF-beta-R II as a marker is confirmed in larger trials, it would offer a potential means of separating EHLA patients into those with a normal amount of the receptor who have the same risk of breast cancer as women in the general population, and those lacking the receptor who have at least a moderately elevated risk and should be monitored more closely with more frequent mammograms and breast exams. It also provides additional genetic information that can be used to counsel women about their risk profile.
An accompanying editorial states that while it would be premature to test breast tissue for TGF-beta II to distinguish "high risk" from "low risk" EHLA patients, further research in this area is likely to lead to attempts at using drugs to prevent breast cancer. This concept is already being applied in women who carry mutations of genes associated with inherited breast cancer. But Matthew J. Ellis, MD, and Daniel F. Hayes, MD, of Georgetown University Medical Center in Washington, D.C., say it is too early to counsel women with benign breast disease about preventive therapy and caution that doing so "might lead to improper overtreatment of a large group of women."
Dupont says studies by others are clearly needed to verify the findings and they should be interpreted with caution, but he tells WebMD that he is fairly confident that the findings "make sense" in terms of what is known of the biology of TGF-beta.
"Enormous increases in understanding about how the body is supposed to work and how it doesn't work when things go wrong hold the promise of greatly increasing our understanding of cancer, and with luck, will lead to something we can do about it," Dupont says.
Vital Information:
*Traditionally, scientists believed that women who get benign breast lesions known as EHLA do not have a higher risk of breast cancer, but this may not be true for all of these patients.
*EHLA patients who have the receptor TGF-beta in fewer than 25% of cells have a three times greater risk of subsequently developing breast cancer compared to those who have the receptor in more than 75% of cells.
*It is still premature to screen EHLA patients for TGF-beta, but if these findings are confirmed in larger studies, women at higher risk could take drugs to prevent breast cancer.
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