Clinical Use of Herceptin Explored

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http://www.cancerpage.com/news/article.asp?id=11076

The Clinical Use of Herceptin Explored


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By Rachael Myers Lowe, Cancerpage
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(ffice:smarttags" /><?xml:namespace prefix = st1 ns = "urn:schemas-microsoft-comJuly 6, 2007</st1:date>) – Up to 30 % of women with invasive breast cancer have disease that over-expresses the HER2 growth factor. HER2 both promotes cell proliferation and puts the breaks on cell death – a hallmark of cancer. HER2 over-expression pointed to a cancer that, until recently, was harder to treat and had a poorer prognosis. With the development of the targeted therapy, trastuzumab (Herceptin), came real hope of prolonged survival for these patients.
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Trastuzumab clogs up the signaling apparatus of HER2, blocking its over-expression and putting the breaks on HER2 dependent cancers. Yet, clinical trials have demonstrated a downside to trastuzumab treatment. Depending on the chemotherapy given with it, between 13% and 27% of the patients developed heart problems. It appears the HER2 performs an important function in helping repair damage to the heart caused by the chemotherapy.
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Writing in this week’s New England Journal of Medicine, Dr. Clifford Hudis, of the Memorial Sloan-Kettering Cancer Center, examines the research and concludes trastuzumab does have a role to play in managing some late and early stage breast cancers and that the clinical trials to date show how important it is to refine how cancers are biologically categorized. In the case of HER2 positive breast cancers, Dr. Hudis believes the evidence supports trastuzumab use in the following circumstances:
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Recurrent metastatic breast cancer – Patients with high-risk aggressive (HER2+, Estrogen - ) cancer should be seriously considered for chemotherapy with trastuzumab because the risk of the cancer far outweighs the potential risk of toxicity to the heart. It’s still a matter of debate whether patients with HER2+ and Estrogen+ cancers benefit from adding trastuzumab before, during, or after hormone therapy.
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Newly diagnosed metastatic breast cancer – Trastuzumab can be considered as mono-therapy before chemotherapy since a small non-randomized trial demonstrated the drug was effective alone and spared the patient the side effects of chemotherapy for as long as six to 18 weeks. Once a cancer has progressed on trastuzumab, however, there’s no evidence to suggest continued use of the drug, even with chemo, is helpful.
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Early stage breast cancer - Trastuzumab might benefit women with early stage HER2+, estrogen- breast cancer and should be considered. But women with small tumors that are HER2+, estrogen+ with no node involvement, the benefits seem” quite modest,” requiring more attention to the potential toxic effect of the trastuzumab on the heart.
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In a letter to the editor in the same NEJM issue, two Canadian researchers report on their trial of 155 women treated for early stage breast cancer between July and December 2005. Of those, 102 received sequential treatment (chemo then trastuzumab), and 53 got concurrent treatment for 52 weeks.
In the sequential treatment group, 22 of the patients experienced heart trouble that required temporary or permanent stopping their trastuzumab. Four women in this group developed suspected or confirmed congestive heart failure.
In those who got concurrent treatment, one woman developed a decline in a measure of how well the heart is pumping blood. She had to stop treatment but then was able to resume. One other woman had congestive heart failure.