C-myc Gene Influences Response to Herceptin®

C-myc Gene Influences Response to Herceptin®

Breast cancer patients who have amplification (extra copies) of the c-myc gene in addition to amplification of the HER2 gene have a lower risk of recurrence and death after treatment with chemotherapy and Herceptin® than patients with amplification of HER2 alone. These results were recently presented at the 28thannual San Antonio Breast Cancer Symposium.

Herceptin is a monoclonal antibody that targets the HER2 protein (the product of the HER2 gene). The HER2 protein plays a role in cellular growth and replication and is overexpressed in roughly 30% of breast cancers. The binding of Herceptin to HER2 prevents or reduces replication of cancer cells. However, due to the cost and potential risks associated with Herceptin, research is focused on identifying the subgroups of patients most likely to benefit from Herceptin.

C-myc is a gene involved in cell division. Dysregulation of the c-myc gene has been reported in many different types of cancer, including breast cancer. Previous research linked c-myc with poor outcomes in patients with HER2-positive breast cancer; this prompted researchers to explore the relationship between c-myc and response to Herceptin.

The researchers evaluated patients in the NSABP B-31 clinical trial, which compared treatment with AC-T (doxorubicin,cyclophosphamide,paclitaxel) to treatment with AC-TH (doxorubicin, cyclophosphamide, paclitaxel, Herceptin). The trial enrolled a total of 1736 patients. Information about c-myc status was available for 1549 of these patients; amplified c-myc was identified in 30%.

Compared to patients with amplification of HER2 alone, patients with amplification of both HER2 and c-myc had dramatically improved outcomes after treatment with Herceptin.

  • Among patients with amplification of both HER2 and c-myc, the addition of Herceptin to chemotherapy reduced the risk of cancer recurrence by 76% and reduced the risk of death by 64%.
  • Among patients with amplification HER2 alone, the addition of Herceptin to chemotherapy reduced the risk of recurrence by 37% and did not reduce the risk of death.

In summary, compared to patients with amplification of HER2 alone, patients with amplification of both HER2 and c-myc have worse outcomes after chemotherapy alone, but better outcomes after chemotherapy and Herceptin. After treatment with Herceptin, 90% of patients with amplification of both HER2 and c-myc survived without cancer recurrence for at least four years.

These results add to a growing body of studies that are honing in on specific subgroups of patients who may achieve significant benefit from Herceptin.

Reference: Kim C, Bryant J, Horne Z, et al. Trastuzumab Sensitivity of Breast Cancer with Co-Amplification of HER2 and cMYC Suggest Pro-Apoptotic Function of Dysregulated cMYC in Vivo. Proceedings from the 28th annual San Antonio Breast Cancer Symposium. December 2005. Abstract #46.

Related News:Addition of Herceptin® to Adjuvant Chemotherapy Improves Breast Cancer Outcomes(12/13/05)

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