Women with clinicopathologic high-risk breast cancer had nearly a 50% reduction in prescription chemotherapy, with no increased risk for metastatic recurrence when a cancer gene-based assay was used to guide treatment decision-making, according to new data presented at the 2016 American Association for Cancer Research meeting.
Patients with high clinical risk and low genetic risk, as assessed by the 70-gene MammaPrint assay, had a 5-year distant metastasis-free survival of 94.4% without chemotherapy versus 95.9% with chemotherapy, a difference that did not reach significance in the intent-to-treat analysis. Patients with low clinical risk but with high genetic risk had a 5-year distant metastasis-free survival of 95.8% with chemotherapy and 95% without chemotherapy.
The use of MammaPrint to inform the utility of adjuvant therapy in clinically high-risk patients was associated with a 46% reduction in prescriptions for chemotherapy, reported Martine J. Piccart, MD, PhD, Head, Medicine Department, Institut Jules Bordet, Brussels, Belgium.
“These results provide level 1A evidence of the clinical utility of MammaPrint for assessing the lack of a clinically relevant chemotherapy benefit in the clinically high-risk population. Patients who were clinically high-risk but genetically low-risk, which included 48% of node-positive patients, had a 5-year distant metastasis-free survival in excess of 94%, whether randomized to adjuvant chemotherapy or no chemotherapy,” said Dr Piccart.
Clinical trials in early-stage breast cancer have shown that adjuvant chemotherapy confers a 2% to 12% absolute improvement in survival. However, chemotherapy has well-recognized toxicities that add to the cost of care.
More than a decade ago, a validated prognostic model that was based on the clinicopathologic risk factors became available to help clinicians decide whether to administer adjuvant chemotherapy to patients with early-stage breast cancer. More recently, tumor gene-expression profiling has emerged as an option for defining breast cancer risk.
MammaPrint Informs Use of Adjuvant Chemotherapy
Dr Piccart reported findings from the MINDACT clinical trial, which compared the clinicopathologic criteria and the 70-gene assay for guiding the use of adjuvant chemotherapy; from 2007 to 2011, investigators in 9 countries enrolled 6693 patients who had undergone surgery for early-stage breast cancer, including those with node-positive disease.
Every patient was evaluated using the clinical prognostic model and the gene-based assay MammaPrint. Patients who had low-risk disease according to both methods received no chemotherapy, and patients with high-risk disease, as assessed by both methods, received chemotherapy. According to Dr Piccart, 3348 patients had discordant results—high-risk disease by one method and low-risk disease by the other method.
After a median follow-up of 5 years, the distant metastasis-free survival for the entire study population was 97.6% for patients with low-risk disease, as assessed by clinical factors and by the gene-based assay versus 90.6% for patients with high-risk disease. Women with high-risk disease tended to have larger tumors, and were more likely to have node-positive and HER2-positive disease than women with low-risk disease.
For the primary statistical analysis, women with high clinical risk and low genetic risk had a 5-year distant metastasis-free survival of 94.7% without chemotherapy, meeting the criteria for a positive study.
Similar to MammaPrint, Oncotype DX is a genomic assay that was developed to help inform use of adjuvant chemotherapy. In the United States, clinicians have access to the MammaPrint and the Oncotype DX recurrence scores, said Nancy E. Davidson, MD, Director, University of Pittsburgh Cancer Institute, PA. Currently, the Oncotype DX recurrence score is more widely used than the MammaPrint recurrence score to predict chemotherapy benefit and the likelihood of distant breast cancer recurrence. Whether results from the MINDACT study influence clinicians’ choice or use of a recurrence score remains to be seen, Dr Davidson said.