Researchers report in the New England Journal of Medicine (NEJM) the strongest evidence yet that some women with early stage breast tumors may not need chemotherapy to effectively treat their cancer. For some women, hormone-based anti-tumor drugs may be all they need to enjoy 98% survival at five years and a 93.8% chance of being free of invasive breast cancer in that time as well.
The key to identifying these women lies with a gene-based test called Oncotype Dx, which scans 21 genes in the tumor to create a dossier of the tumor’s strengths and weaknesses. The information helps doctors to determine how potentially aggressive, or not, a tumor might be. Allowed on the market as a clinical laboratory test in 2004, it produces a recurrence score from 0 to 100 and helps doctors determine whether women should be treated with chemotherapy. Lower scores generally indicate that hormone-based drug therapies are enough, while higher recurrence scores push physicians to consider chemotherapy to lower the risk of the cancer returning.
But studies to date have tested Oncotype Dx’s predictive capabilities using archived samples of tumors. No studies have put Oncotype Dx to the test by randomly assigning women to hormone therapy alone without chemotherapy to measure their risk of recurrence after five years.
That’s what the trial described in the NEJM—the Trail Assigning Individualized Options for Treatment (TAILORx)—was designed to do. TAILORx included 10,253 women diagnosed with breast cancer that possessed hormone receptors (meaning the tumors would respond to hormone therapies) but had not spread to their lymph nodes and were anywhere from 1 cm to 1.5 cm in size. The tumors ranged from low grade, which are not as aggressive, to higher grade cancers, which tend to grow faster and contain more abnormal cells. Current guidelines suggest that younger women diagnosed with such breast tumors, or women with larger and higher grade tumors, receive both hormone therapy and chemotherapy to prevent recurrence.
But TAILORx randomly assigned women with an Oncotype Dx recurrence score of less than 11 to just take hormone therapy alone, and skip the chemo. About 16% of the women in the study fell into this category, and after five years, they did remarkably well. Not only did 99% of them survive to five years, but they had a less than 2% risk of having a recurrence either locally or in other parts of the body.
“What we’ve shown is that if you have a low recurrence score, you do really, really well with [hormone] therapy alone,” says Dr. Joseph Sporano, associate chairman of the oncology at Montefiore Medical Center and lead author of the study. “The likelihood of responding to chemotherapy would be nill. So I think we can be much more confident in making the recommendation to just use [hormone] therapy alone especially in patients where we might have been a little skittish about recommending sparing chemotherapy.”
What’s more, the recurrence score seemed to be more predictive of who could be spared chemo compared to traditional factors that doctors use, such as tumor grade. The benefit from hormone therapy alone was the same for women no matter what their tumor grade.
Why did the study focus on women with scores under 11? Sporano admits there’s nothing truly magic about that number, except that previous studies suggested that’s the point above which tumors start to become aggressive. But the TAILORx will continue to study women with scores between 11 and 25, which represents a much larger proportion of breast cancer patients (nearly 70% of women in the study fell into this range) as well to determine where the cutpoint for hormone-treatment alone should be. The group with scores between 11 and 25 have been randomly split between those getting the drug therapy alone and those receiving the drugs and chemotherapy.
“What we are uncertain about is where to draw the cutpoint,” says Sporano. “How low can we go to that cutpoint? That’s an unanswered question that will be addressed by the ongoing trial.”
The study will also investigate how useful the test can be for women who might have some cancer cells in their lymph nodes.
The findings should help cancer doctors to have more confidence in recommending that certain women skip chemotherapy, but Sporano admits that this might be a difficult hurdle to overcome. First, the test isn’t universally used, since it costs $3,500. Doctors tend to rely on the assay when they want more information before deciding whether to recommend chemotherapy to their patients. And the instinct to rely on logical features, such as the tumor’s size and grade, may be too strong to challenge. “There may be a tendency to discount the results of the recurrence scores in patients who are younger and with larger tumors or higher grade tumors,” he says. “But the results of this study suggest that information should not be discounted. These patients can do really, really well with this information.”