THURSDAY, April 17, 2003 (HealthDayNews) -- The discovery of a new molecular pathway involved in the spread of breast cancer may have far-reaching public health implications for women, possibly influencing the way breast cancer is treated.
That's the word from scientists at Emory University and The Winship Cancer Institute, where the latest research not only offers a new understanding of what makes certain breast cancers more aggressive, but also how some medications -- particularly those used to reduce cancer risks -- might ultimately contribute to its spread.
"We defined a pathway that regulates invasion [of cancer cells] and what we see is that some of the traditional anti-cancer drugs knock out this pathway," says Paul Wade, an assistant professor of pathology and laboratory medicine at Emory University School of Medicine.
Wade oversaw the research, which appears in the April 17 issue of Cell.
By examining laboratory cancer cell lines, the study focused on uncovering genetic differences between tumors that are "estrogen-sensitive" -- encouraged by estrogen to grow -- and those that are not. In the process, Wade and his group came upon a protein pathway known as MTA3, which, among other things, regulates a molecule identified as E-cadherin. This acts as a kind of biological "glue" that holds normal cells together, keeping them from rapidly dividing and forming tumors.
In tumors that are estrogen-sensitive, Wade says it's clear the MTA3 pathway is active -- along with the "glue" molecule holding cells together. This may be one reason why these tumors appear less aggressive and less likely to spread, he adds.
Conversely, they found that when a tumor was "estrogen receptor negative" -- meaning it did not require estrogen to grow -- the MT3A pathway was shut down and the E-cadherin protein didn't function at all.
This, says Wade, may be one reason why estrogen-negative tumors appear more virulent.
However, the inferences drawn from this study don't stop there. Wade believes the findings also have implications concerning popular anti-cancer drugs known as SERMs -- selective estrogen receptor modulators -- which include medications such as tamoxifen.
Frequently recommended following breast cancer treatment to reduce future risk of the disease, SERMs are thought to work by latching onto breast cells that would normally attract the tumor-promoting estrogen. When estrogen can't "log on," the thinking is the tumors won't grow.
What Wade now proposes is that part of the way in which drugs such as tamoxifen do their job is by disabling the MT3A pathway -- in a sense, turning a estrogen-positive tumor into one that is estrogen-negative.
In the process, SERMS may also disable the E-cadherin "glue-like" protein -- and that, in turn, may ultimately turn any future cancers more aggressive, Wade says.
One of the inevitable consequences of long-term SERM therapy is that cancer cells do develop a resistance to the drugs. Wade believes it is at this point that the less desirable effects demonstrated by the new research may kick in.
"We are not saying these are bad drugs -- it just means they can do more than one thing and one of the consequences of the therapy is a loss of the necessary pathway we defined," Wade says.
New York University breast cancer expert Dr. Julia Smith calls the research as important as it is fascinating.
"I think that these are, in fact, the kinds of molecular issues that, as we come to understand, will truly change our ability to treat not only breast cancer, but probably all cancers," Smith says.
However, she is less sure of Wade's conclusions regarding drugs such as tamoxifen.
"Their statement that there could be potentially negative results from compounds that affect cell architecture -- that tamoxifen could have deleterious effects -- right now, this is a leap of faith that is not yet proven in this research," Smith says.
She advises women who are taking tamoxifen not to worry, and not to stop the drug based on this one finding.
Wade agrees more research is in order. However, he believes it will only reinforce the idea that calls for more judicious use of SERM drugs -- not only in the treatment of breast cancer, but also in the treatment of other diseases. They include osteoporosis, for which certain SERM medications are currently prescribed.
"It's a new pathway, something that we think is important, and it's impacted by drugs that are used by an awful lot of women," says Wade. "So ultimately, it's going to be important for us to examine the consequences of treating women with these drugs in terms of what happens with the pathway that we've defined."
More information
To learn more about the various types of breast cancer, visit BreastCancer.org. For more information on tamoxifen, check with the National Cancer Institute.
