HER2 and Topo II Status Affects Response to Anthracycline Chemo

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Genes in breast cancer cells affect how the cancer grows and how it responds to certain treatments. A study found that HER2-negative breast cancers are usually topo II-negative. This means that the cancers don't have an abnormal topoisomerase II alpha gene (called topo II or TOP2A for short).

Cancers that are HER2-positive and topo II-positive respond better to chemotherapy therapy regimens that include an anthracycline such as Adriamycin (chemical name: doxorubicin). Cancers that are HER2-negative and topo II-negative don't seem to respond to anthracyclines, which means they could be treated with other chemotherapy medicines that have fewer severe side effects.

Anthracyclines work by damaging cancer cell genes, which causes the cells to weaken or die. Other anthracyclines are daunorubicin (brand names: Cerubidine, DaunoXome), Doxil (chemical name: doxorubicin) and Ellence (chemical name: epirubicin). CEF, which uses Ellence, Cytoxan (chemical name: cyclophosphamide), and flourouracil (also known as 5FU), is a common chemotherapy regimen containing an anthracycline.

In this study, the researchers compared the results of treatments for women diagnosed with topo II-negative and topo II-positive breast cancer:

  • Women diagnosed with topo II-negative cancer treated with anthracycline-based chemotherapy had the same risk of the breast cancer coming back and the same chances of surviving breast cancer as women treated with chemotherapy that DIDN'T include an anthracycline.
  • Women diagnosed with topo II-positive breast cancer treated with anthracycline-based chemotherapy had a lower risk of the cancer coming back and better survival chances than women treated with chemotherapy that DIDN'T include an anthracycline.

Right now, testing for an abnormal topo II gene isn't common. But almost all breast cancers are tested for HER2 status. This research found that breast cancers that are topo II-positive are usually HER2-positive and cancers that are topo II-negative are usually HER2-negative. So HER2 status is a good way to figure out topo II status.

This research is important because anthracyclines tend to cause more serious side effects (including possible heart damage) than some other chemotherapy medicines. So using anthracycline-based chemotherapy only makes sense for women who will benefit from it. This and other studies suggest that anthracycline-based chemotherapy should be used to treat only HER2-positive breast cancers.

If you've been diagnosed with breast cancer and chemotherapy will be part of your treatment plan, talk to your doctor about the HER2 status of the cancer and ask about the type of chemotherapy medicines being considered for you. You may want to mention that this and other studies suggest that the risks of treatment with an anthracycline make sense only if the cancer is HER2-positive. Together you and your doctor can decide on a chemotherapy treatment plan that makes the most sense for you and your unique situation.

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