Studies Question a Breast Cancer Chemo Mainstay

Dec. 14, 2007— -- Support for a traditional mainstay of breast cancer chemotherapy treatment may erode after two new studies find that the drug may only benefit a subset of women with the disease.

Anthracyclines -- a commonly used class of chemotherapy drugs that also have antibiotic properties -- can cause unpleasant side effects such as nausea, vomiting and, in some cases, serious heart problems.

Being able to reliably tell which breast cancer patients would not likely benefit from the drugs would help doctors spare many women these toxic side effects.

Results from two studies presented Thursday at the 30th annual San Antonio Breast Cancer Symposium now reveal that only women with HER2 positive breast cancer -- a subset which accounts for only about 8 percent of women with breast cancer worldwide -- will benefit significantly from standard anthracycline-based chemotherapy.

Moreover, the research suggests that a different, investigative approach to chemo, which combines Taxotere (doxetaxel)-based therapy with cyclophosphamide, may offer better chances of survival -- along with less severe side effects.

Anthracycline-based therapies spurred controversy within the medical community when they were first introduced nearly 30 years ago. But the contention over the benefit-to-risk ratio of anthracyclines was put to rest when the Oxford Review published evidence supporting this treatment in 1993, citing that use of the anthracycline treatment regimen improved chances of overall survival by 4 to 5 percent.

But Dr. Dennis Slamon, lead investigator of the study presented at SABCS Thursday and chief of the division of hematology/oncology at UCLA's Jonsson Comprehensive Cancer Center, said that his study found that there was actually no benefit whatsoever from the anthracycline treatment in breast cancer patients who did not have HER2 positive breast cancer.

"It's a subgroup of a subgroup [of breast cancer patients] who have this [HER2 positive] alteration that gives us huge benefit of anthracycline, giving us the illusion that in all of breast cancer there's this 4 to 5 percent benefit," he said. "In fact, there's a 30 percent [improvement in overall survival] in this small subgroup that was dragging the whole group up. … And that was dictating treatment decisions for the last almost three decades."

A New Chemo Option?

In the second study, researchers looked at more than 1,000 breast cancer patients who either took a combination of an anthracycline and cyclophosphamide (AC) or the investigational Taxotere and cyclophosphamide (TC) treatment.

What they found was that women treated with TC had a 31 percent reduction in death risk. Moreover, women treated with TC were 26 percent less likely to have their breast cancer return.

"The take-home message is that we have developed a chemotherapy regimen that really is really practice-changing," said Dr. Stephen Jones, lead investigator of the study and medical director and co-chairman of the Breast Cancer Research Committee of U.S. Oncology Research Inc.

"This treatment with Taxotere-cyclophosphamide is more effective than one of the standard regimens that has been standard for more than 30 years, and has less potentially serious long-term side effects as well as immediate side effects."

Until now, a more effective treatment than standard anthracycline-based chemo has never been available.

Jones, himself a pioneer in the development of anthracycline-based chemotherapy treatment nearly 30 years ago, said the benefit from the TC combination was observed across all patient groups, regardless of their age or even the type of breast cancer they had.

"What we saw was benefit across all subgroups," he said. "We did an analysis of HER2 patients … and saw that they benefited better [from TC] than with standard treatment. We looked at HER2 negative patients, HER2 receptor positive and node negative patients -- really in every subgroup we looked at TC was a better treatment."

Dr. Stefan Gluck, professor of medicine in the division of hematology/oncology at the University of Miami, said that the new drug may be the key to offering effective treatment without the heart dangers posed by anthracyclines.

"Consequently, I have been using these regimens for the last two years or so," he said.

More Research Needed

While many doctors believe these two studies have the power to change the standard of care of breast cancer patients, some say that further research into Taxotere is required before it will replace anthracyclines as the standard of treatment.

"The only trouble with the studies was the fact that current treatment is not AC [alone] but AC followed by Taxotere," said Dr. Susan Love, president and medical director of the Dr. Susan Love Breast Cancer Research Foundation. "Since none of the studies addressed whether both was better than either alone, it is hard to say whether it will be practice-changing."

Despite the continued doubt regarding the removal of anthracycline-based regimens from breast cancer treatment, Slamon believes his and Jones' studies reveal a crucial message about the current standard of breast cancer treatment.

"When you put [my study] in the context of what Dr. Jones presented before me, you can begin to see that understanding the molecular characterization of the tumor allows us to throw away this one-size-fits-all approach [to breast cancer treatment] where everyone receives an anthracycline, and use specific therapies just for the right subclass of breast cancer [patients]," Slamon said.