Sunday, February 28, 2010

Continuing on with Herceptin

Although done with chemotherapy, I will continue on until mid-November with the Herceptin infusions. So, I've been doing more research into Herceptin or Trastuzumab. Trastuzumab (trade name Herceptin) is a monoclonal antibody that interferes with the HER2/neu receptor. The HER receptors are proteins that are embedded in the cell membrane and communicate molecular signals from outside the cell to inside the cell, and turn genes on and off. The HER proteins regulate cell growth, survival, adhesion, migration, and differentiation—functions that are amplified or weakened in cancer cells. In some cancers, notably some breast cancers, HER2 is stuck in the "on" position, and causes breast cells to reproduce uncontrollably, causing breast cancer. Trastuzumab reverses the effects of an overactive HER2 receptor.
The original studies of trastuzumab showed that it improved survival in late-stage (metastatic) breast cancer, but there is controversy over whether trastuzumab is effective in earlier stage breast cancer. Trastuzumab is also controversial because of its cost, as much as $100,000 per year [yikes!], and while certain private insurance companies in the U.S. and government health care systems in Canada, the U.K. and elsewhere have refused to pay for trastuzumab for certain patients, some companies have since accepted trastuzumab treatment as a covered preventative treatment.
Since it is possible to determine the "erbB2 status" of a tumour, that information can be used to predict efficacy of treatment with trastuzumab. If it is determined that a tumour is overexpressing the erbB2 oncogene and the patient has no significant pre-existing heart disease, then a patient is eligible for treatment with trastuzumab. It is surprising that although trastuzumab has great affinity for the receptor and the fact that such a high dose can be administered (due to its low toxicity) 70% of HER2+ patients do not respond to treatment. In fact resistance is developed rapidly by treatment, in virtually all patients [so the odds are against me?].
Some recent clinical trials have found trastuzumab reduces the risk of relapse in breast cancer patients by 50% when given in the adjuvant setting (i.e. after breast cancer surgery, before the cancer has spread any further) for one year. Even among the 20% of first-time breast cancer patients for whom trastuzumab is an appropriate treatment, the actual net benefits are not overwhelming when viewed in terms of all-cause mortality. All-cause mortality helps balance a reduced risk of death from cancer against the increased risk of death from a treatment's side effects. Repeated, large-scale studies show that it is usually necessary to treat between 25 and 100 patients to prevent a single death during the next two to four years. For each life saved, between ten and 25 patients will develop heart disease; despite effective treatments, some of these patients will die from heart disease [Great, even more good news!]
The optimal duration of adjuvant trastuzumab is currently unknown. One year of treatment is generally accepted as the ideal length of therapy based on current clinical trial evidence that demonstrated the superiority of one year treatment over none. However, a small Finnish trial also showed similar improvement with nine weeks' of treatment over no therapy. Due to the lack of direct head-to-head comparison in clinical trials, it is unknown whether a shorter duration of treatment may be just as effective (with less side effects) than the current accepted practice of treatment for one year. [I just love being a guinea pig] Debate about treatment duration has become a relevant issue for many public health policy makers due to the high financial costs involved in the administration of this treatment for one year. Don't you just love modern medicine?

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