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Breast cancers that contain alterations in a gene known as TOP2A tend to respond better to an anthracycline-containing chemotherapy regimen than to a non-anthracycline-containing chemotherapy regimen. These results were published in the Journal of the National Cancer Institute.

Chemotherapy is commonly used in the adjuvant (post-surgery) treatment of early-stage breast cancer. Some studies have suggested that chemotherapy regimens that include an anthracycline (drugs such as doxorubicin and epirubicin) produce better outcomes than older chemotherapy regimens such as CMF (cyclophosphamide, methotrexate, 5-fluorouracil) that do not include an anthracycline. More recent research, however, suggests that the benefit of anthracycline-containing regimens may apply only to certain subgroups of patients. Being able to predict who will benefit from an anthracycline-containing regimen is important because anthracyclines can produce serious side effects.

One factor that had been linked with anthracycline benefit is HER2 status. Cancers that are HER2-positive tend to respond better to anthracycline-containing chemotherapy regimens than to non-anthracycline-containing chemotherapy regimens.

TOP2A is a gene that lies close to the HER2 gene, and some research has suggested that it may be more strongly linked with anthracycline benefit than HER2.

To explore the role of TOP2A gene alterations in relation to anthracycline benefit, researchers evaluated tumor samples from 438 premenopausal women with node-positive breast cancer. The women were participants in a clinical trial that compared two adjuvant chemotherapy regimens: CEF and CMF. CEF is an anthracycline-containing chemotherapy regimen that consists of cyclophosphamide, epirubicin, and 5-fluorouracil. CMF is a non-anthracycline-containing regimen that consists of cyclophosphamide, methotrexate, and 5-fluorouracil.

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Eighteen percent of the women had cancers that contained TOP2A alterations.

  • Among women with TOP2A alterations, treatment with CEF (the anthracycline-containing regimen) resulted in fewer recurrences and better overall survival than treatment with CMF.
  • Among women without TOP2A alternations, the two chemotherapy regimens had similar effectiveness.

These results suggest that TOP2A gene alterations are linked with anthracycline responsiveness. The increased responsiveness is similar to what is seen in patients with HER2-positive cancers.

These results also suggest that for cancers with normal versions of the HER2 and TOP2A genes, anthracycline-containing regimens are no more effective than less toxic, non-anthracycline-containing regimens.

Reference: O’Malley FP, Chia S, Tu D et al. Topoisomerase II alpha and responsiveness of breast cancer to adjuvant chemotherapy. Journal of the National Cancer Institute. 2009;101:644-650.

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