TOP2A alterations linked with improved survival after anthracycline-based therapy

Topoisomerase II alpha gene alterations were associated with better outcomes after anthracycline-based therapy compared with nonanthracycline-based regimens among patients with node-positive breast cancer, according to data from a recent analysis.

Previous studies have demonstrated that women with gene amplification or protein overexpressionHER2 benefit more from chemotherapies containing anthracycline compared with those without. However, some speculation exists regarding whether TOP2A is responsible for the difference in treatment response.

Researchers examined 438 tumors from 710 premenopausal women with node-positive disease. Patients were randomly assigned to cyclophosphamide, epirubicin and 5-FU or cyclophosphamide, methotrexate and 5-FU as part of the National Cancer Institute of Canada Clinical Trials Group Mammary 5 trial. The researchers analyzed the association of TOP2A and HER2 status with recurrence-free survival and OS in both treatment groups.

In patients assigned to anthracycline-based chemotherapy, TOP2A alterations were associated with improved five-year recurrence-free survival and five-year OS compared the nonanthracycline-based arm. Patients with normal TOP2A tumors had a similar response to both regimens.

Additionally, the adjusted test for the interaction between HER2 status and treatment was P=.008 for recurrence-free survival and P=.02 for OS. For TOP2A the adjusted test for interaction was P=.09 for recurrence-free survival and P=.02 for OS.

In an accompanying editorial, Dennis J. Slamon, MD, PhD, division of hematology/oncology, department of medicine and the Jonsson Comprehensive Cancer Center at UCLA School of Medicine and Michael F. Press, MD, professor in the department of pathology, Keck School of Medicine at the University of Southern California in Los Angeles, discuss data in the literature that demonstrate the association between HER2 and anthracycline-based therapy.

“A question remains as to whether patients with HER2 amplification and TOP2A co-amplification will still benefit incrementally from anthracyclines now that we can use drugs like trastuzumab or lapatinib, which target the HER2 alteration directly,” they wrote. “This will require analysis of recently completed and ongoing large adjuvant studies that compare anthracycline-based regimens with nonanthracycline regimens in combination with these HER2 antagonists.”

O’Malley FP. J Natl Cancer Inst. 2009;101:644-650.