June 2016, Vol. 5, No. 5
Chemotherapy Use in Breast Cancer Declines with Gene-Based Assay
Women with clinicopathologic high-risk breast cancer received chemotherapy almost half as often with no increased risk of metastatic recurrence when a cancer gene assay was used to guide decision-making, results of a randomized trial showed.
Patients at low risk by the 70-gene MammaPrint assay had a 5-year distant metastasis-free survival (DMFS) of 94.4% without chemotherapy versus 95.9% with chemotherapy, a difference that did not reach statistical significance. In the setting of clinical low risk and a high-risk score by the assay, the 5-year DMFS was 95.8% with chemotherapy and 95.0% without.
Use of the gene assay to inform use of adjuvant therapy in clinically high-risk patients was associated with a 46% reduction in prescriptions for chemotherapy, Martine Piccart, MD, PhD, reported at the American Association for Cancer Research Annual Meeting.
“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,” said Dr Piccart, Director of Medical Oncology at the Jules Bordet Institute in Brussels, Belgium. “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.”
Clinical trials in early 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 based on clinicopathologic risk factors became available as an aid to deciding whether to administer adjuvant chemotherapy to a patient with early breast cancer. More recently, tumor gene expression profiling has emerged as an option for defining breast cancer risk.
Dr Piccart reported findings from the MINDACT trial, which compared the clinicopathologic criteria with the 70-gene assay for providing guidance about the use of adjuvant chemotherapy. From 2007 to 2011, investigators in 9 countries enrolled 6693 patients who had undergone surgery for early breast cancer, including node-positive disease.
Every patient was evaluated by the clinical prognostic model and the genetic test. Patients who had low-risk disease by both methods received no chemotherapy, and all patients who were high risk by both methods did receive chemotherapy. Dr Piccart said 3348 patients had discordant results—high risk by one method, low risk by the other.
The patients with discordant results received radiation therapy and were randomized to clinical or genetic risk assessment to decide whether they would receive adjuvant chemotherapy. The primary end point was 5-year DMFS, and the trial was considered positive if the results showed a 5-year DMFS of 92.0% in the subgroup of patients who had clinically high-risk disease but had a low risk of recurrence by the gene assay.
After a median follow-up of 5 years, DMFS for the entire study population was 97.6% for patients who had low-risk disease by clinical/pathologic factors and the gene test versus 90.6% for those who had high-risk disease by both criteria. Dr Piccart said women with high-risk disease tended to have larger tumors and were more likely to have node-positive and HER2-positive disease.
For the primary analysis, women with high clinical/low genetic risk had a 5-year DMFS of 94.7% without chemotherapy, meeting the statistical criteria for a positive study.
In the United States, clinicians have access to both the MammaPrint and the Oncotype DX gene-based recurrence scores, said Nancy Davidson, MD, Professor of Oncology at the University of Pittsburgh Cancer Institute, PA. Currently, Oncotype DX is more widely used. Whether the MINDACT results influence clinicians’ choice or use of a recurrence score remains to be seen, she said.
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