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Approximately 30 percent of breast cancers have
an amplification of the HER2/neu gene or overexpression of its protein
product. Overexpression of this receptor in breast cancer is associated
with increased disease recurrence and worse prognosis.
Because of its
prognostic role as well as its ability to predict response to trastuzumab (Herceptin) breast tumors are routinely checked for
overexpression of HER2/neu. Overexpression also occurs in other cancer
such as ovarian cancer, stomach cancer, and biologically aggressive
forms of uterine cancer, such as uterine serous endometrial carcinoma. |
In clinical usage, HER2/neu is important as the
target of the monoclonal antibody trastuzumab (marketed as Herceptin).
Trastuzumab is effective only in breast cancer where the HER2/neu
receptor is overexpressed.
Overexpression of the HER2 gene can be suppressed
by the amplification of other genes and the use of the drug Herceptin.
Research is currently being conducted to discover which disregulated
genes may have this desired effect. Another monoclonal antibody,
Pertuzumab. which inhibits dimerization of HER2 and HER3 receptors, is
in advanced clinical trials. Trials combining these durgs with
chemotherapy are being devloped as noted below
The NEOSPHERE study (Neoadjuvant Study of
Pertuzumab and Herceptin in an Early Regimen Evaluation) is a
randomized multicentre, international Phase II study that was conducted
in 78 centres worldwide (except the USA) in 417 women with newly
diagnosed HER2-positive early, inflammatory or locally advanced breast
cancer who had never received Herceptin. Prior to surgery (neoadjuvant
treatment) these women were randomized to four study arms. The primary
endpoint was complete tumour disappearance at time of surgery (pathological
complete response , pCR) and the results were:
- pCR of 29,0 percent for Herceptin and
docetaxel
- pCR
of 45,8 percent for Herceptin, pertuzumab and docetaxel
- pCR of 16,8 percent for Herceptin and
pertuzumab
- pCR of 24,0 percent for pertuzumab and
docetaxel
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