By Robert Bazell
Chief science and health correspondent
June 5, 2007
What if an estimated 100,000 breast cancer patients got drugs that did nothing to combat their cancer, but put them at risk for heart failure and leukemia?
That is the implication of new research that was presented in private session at this week’s meeting of the American Society of Clinical Oncology(ASCO) in Chicago.
The research, from Dr. Dennis Slamon, chief of oncology at the University of California, Los Angeles, suggests that the most widely used chemotherapy drugs may not benefit most women. Although the research hasn’t been published or peer-reviewed yet, it is expected to be soon.
The drugs are a common class of treatments called anthracyclines, including doxorubicin, epirubicin, and mitoxantrone. Since their introduction in the 1980s anthracyclines have replaced older chemotherapy drugs in the combination therapies given to women. Administered in the months after surgery and radiation, the chemotherapy is intended to reduce the chances of a life-threatening recurrence of cancer, especially in women at high risk for relapse.
Early on, researchers understood that anthracyclines could cause heart failure in some patients. Recently, evidence has accumulated about the additional risk of leukemia, which can strike years or decades after the treatment.
Evidence for the effectiveness of anthracyclines versus the older drugs remained murky. Then, a 1998 meta-analysis (a study of all the previous studies) found the anthracyclines did a 4 percent better job at preventing recurrence. Despite their side effects, that study elevated the drugs to the standard of care.
Treating many to help few The UCLA research questions that treatment.
Slamon played a key role in the discovery and development of the hugely successful breast cancer drug Herceptin. Herceptin, which changed the way the disease is treated, specifically targets a gene called Her-2 that is overexpressed in 20 percent to 25 percent of breast cancers (a gene is overexpressed when its effect becomes excessive in the body). Herceptin’s success proved that breast cancer is not one disease, but many, with each benefiting from a tailored treatment.
In this latest study, Slamon looked at a more recently discovered gene called Topoll-2, which is sometimes, but not always, overexpressed along with Her-2. Anthracyclines stop breast cancer because they target Topoll-2.
Slamon examined tissue samples from more than 2,000 women who took part in seven clinical trials. His analysis showed that anthracyclines work only in women who overexpress the Topoll-2 gene. Such women account for 8 percent of breast cancer cases.
The anthracyclines — with all their side effects — have almost no effect in 92 percent of breast cancer cases.
“It seems apparent that we are treating patients who don’t need the drug to get at that group who have a huge benefit,” Slamon told me. “And now we need to direct our therapy and target it more specifically.”
Exciting result’ Even when other cancer doctors were willing to use anthracyclines only as targeted therapy, they couldn’t. There is no commercial test yet for the Topoll-2 gene, although there likely will be in a few months.
Nevertheless, Johns Hopkins breast cancer specialist Dr. Nancy Davidson calls the findings “an exciting result.”
“It’s early; it’s provocative. We are waiting to see it go through peer review in the usual fashion,” says Davidson, who is incoming president of ASCO. “But there’s a lot of buzz.”
Fran Visco, a cancer survivor and president of the National Breast Cancer Coalition, agrees the work needs to be published and peer-reviewed — very soon.
“This is going to be a sea change in how we treat breast cancer,” she told me. “There is no reason we shouldn’t be moving very quickly to publish it and quickly to figure out how we’re going to implement it in practice. Women deserve no less.”