The gene expression-based predictor of response is 75 percent accurate in forecasting which women with newly diagnosed, untreated breast cancer will experience complete eradication of the cancer by taking weekly paclitaxel followed by 5-fluorouracil, doxorubicin and cyclophosphamide (FAC) chemotherapy – one of about six different chemotherapy regimens now in use, say investigators at The University of Texas M. D. Anderson Cancer Center.
Knowing if chemotherapy will work before it is given to breast cancer patients represents a major advance in care because it eliminates the time-consuming and potentially toxic trial and error that patients must go through to find effective treatment, say the researchers, who presented their results at the annual meeting of the American Society of Clinical Oncology.
"If these results continue to hold up in larger validation studies, it can fundamentally change the way that chemotherapy is selected for patients," says the lead investigator, Lajos Pusztai, M.D., Ph.D., assistant professor of breast medical oncology at M. D. Anderson.
"We will be able to select from a large number of seemingly appropriate chemotherapy choices the regimen that is most likely to cure an individual at the time of diagnosis," he says.
The goal is to develop gene screens for all of the most common types of chemotherapy regimens used to treat newly diagnosed breast cancer, so that physicians will know which drugs will work before a patient uses it, says Pusztai. "This is a small 'proof-of-principle' study which represents an important step in the direction of personalized medicine."
This test, as well as others envisioned, will require a small needle biopsy of the cancer that could be obtained along with the diagnostic biopsy.
M. D. Anderson researchers worked in collaboration with scientists at Millennium Pharmaceuticals to develop the test, which used biopsy tissue from 24 patients with early stage breast cancer. Genetic information of the cancer from these samples was extracted and tested on DNA microarrays containing 30,000 human genetic transcripts.
This method allowed the investigators to examine the gene expression profile of each cancer and identify a profile that is associated with "extreme" sensitivity to paclitaxel FAC chemotherapy. Extreme chemotherapy sensitivity was defined as the complete eradication of cancer from the breast by preoperative chemotherapy.
Other investigators have previously shown that patients who experience such pathologic complete response are most likely cured from their disease," Pusztai says. "However, until now, it has been impossible to predict which chemotherapy regimens would most likely produce this very favorable outcome in a particular individual."
The researchers developed the genetic markers into a test and evaluated it prospectively in 21 newly diagnosed patients. The gene screen correctly predicted pathologic outcome after treatment in 15 patients – a 71 percent accuracy rate – and was 75 percent correct to predict pathologic complete response.
Since then, Pusztai and other M. D. Anderson researchers have used a commercially available DNA microarray "that is widely available to other investigators, and can be manufactured in the future as a diagnostic test" to replicate their results. The investigators are currently testing this commercially available method in a larger randomized study at M. D. Anderson. He adds that if this larger clinical trial continues to validate these findings, the predictive test may be available for widespread use in two to three years.
Contact: Laura Sussman or Stephanie Dedeaux, (713) 792-0655