HER2-positive people who may not need Herceptin?

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Question from ShirleyR: What are your views on the latest findings that seem to show that HER2+ patients who also test positive for topoisomerase IIA do not require Herceptin if they have had Adriamycin as part of their chemo regimen?
Answers - Ruth Oratz, M.D., F.A.C.P. This raises a very interesting molecular biology question in the management of HER2+ breast cancer. We know that in tumors that have high levels of the HER2/neu receptor, treatment with Herceptin (or trastuzumab, the generic name) is very beneficial. This is true in the setting of metastatic disease as well as in the early stage setting. Topoisomerase, also called topo II or TOP2A, is an enzyme that repairs abnormalities in DNA. The gene that codes for topo II is adjacent to the gene that codes for HER2/neu. There is some question about the relationship between amplifications of the HER2/neu gene and alterations or amplifications of the topo II gene. There is some data to suggest that if topo II is amplified, the tumor cell is very sensitive to treatment with Adriamycin (chemical name: doxorubicin) and it has been suggested that Adriamycin is more effective in cancers that are HER2-positive than in those that are HER2-negative. However, the consensus amongst medical oncologists is that if the tumor overexpresses HER2/neu, HER2 targeted therapies with Herceptin or Tykerb (chemical name: lapatinib) is indicated. Most medical oncologists would not recommend the use of only Adriamycin in this setting. There is more research being done on the relationship of HER2/neu and topo II, and the question of whether or not Adriamycin is required in the treatment of HER2-positive breast cancer. There are several chemotherapy regimens which do not contain Adriamycin and which do contain HER2-targeted therapy both for metastatic disease as well as early stage breast cancer. These have been shown to be equally as effective as a regimen that does contain Adriamycin. The ones that do not and the ones that do are equal in their clinical efficacy. Certainly, more work is going to be done investigating the molecular biology of HER2/neu and topo II. As of now, our clinical practice and treatment decisions are not being based on topo II levels or topo II expressions.

The Ask-the-Expert Online Conference called Updates From the 2008 San Antonio Breast Cancer Symposium featured Ruth Oratz, M.D., F.A.C.P. and Carol Kaplan, M.D. answering your questions about the latest updates on breast cancer risk, screening techniques, treatment options, and more.

Editor's Note: This conference took place in December 2008.

The materials presented in these conferences do not necessarily reflect the views of Breastcancer.org. A qualified healthcare professional should be consulted before using any therapeutic product or regimen discussed. All readers should verify all information and data before employing any therapies described here.

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