Does looking backward help us to go forward?

Over the last thirty years, there have been many different chemotherapy regimens to prevent breast cancer recurrence in patients who have been treated optimally with mastectomy or radiation.  Referred to as adjuvant chemotherapy, its goal is to eradicate small numbers of tumor cells that may remain behind after initial therapy.
In some cases, newer adjuvant drugs have replaced older ones when randomized studies have demonstrated superiority.  In other cases, the duration or the intensity of chemotherapy has changed over time, again based on the results of randomized clinical trials. 

In recent years, a regimen of Adriamycin and Cytoxan followed by Taxol has become the standard of care in many cancer centers, including the Willmar Cancer Center.  This program has shown its superiority over earlier, less aggressive regimens, thus its acceptance by physicians and patients alike.  However, this “core belief” was rattled recently by an article published this past October in the New England Journal of Medicine.

The article reported a unique study in which breast cancer tissue taken from thousands of women in the late 1990s was subjected to modern analysis, utilizing new information and new techniques to re-examine hormone receptors and to analyze for the presence of the HER-2 growth factor of those tumors.  (While we have known for many years that positive hormone receptors indicate a better prognosis in breast cancers, more recently we have understood how a positive HER-2 test indicates a more aggressive form of the disease.)

The study then looked at the clinical course of patients who had Taxol as part of their chemotherapy program compared to those who did not.  Interestingly, it appeared that the addition of Taxol did not improve the outcome in situations where the hormone receptors were positive and the HER-2 negative.  Taxol offered slight improvement if hormone receptors were negative and the HER-2 negative.  Real benefit from the addition of Taxol seemed to occur mainly in those patients who were HER-2 positive.  Since HER-2 is present in only a minority of breast cancer patients, the study raised the question as to whether we should continue using Taxol in all patients.

This was front-page news.  Understandably, patients began calling their physicians the very day the study was published.  They wondered why their past treatments had included Taxol, or why they had to take the drug now.  It is a tough question to answer.  Physicians and patients of course want to avoid as much chemotherapy toxicity as possible.  If this could be accomplished by leaving out a drug with potential neurologic, allergic, and infection complications – and without compromising the probability of cure – everyone might agree to omit it.

The article itself, however, cautioned against rushing to judgment about the role of Taxol, as did an accompanying editorial opinion.  There was a plea for caution in applying the results of this one study to the prescription of chemotherapy programs for current and future patients.  A single study should not bring about a major change in practice, it was argued, until further studies corroborated the first.  Further, we usually place more confidence in prospective (future looking) studies than in retrospective (hindsight) studies – and this was a retrospective study.  Nonetheless, it is not wise to disregard a possible “early signal” brought out by this study.

For the moment, the best decisions about Taxol will be made when physicians and patients sit down and discuss what is known both from prospective and retrospective studies.  While “the facts” are not as clear as we would like them to be and may not lead to an easy conclusion, most patients can become comfortable with a strategy that addresses their own unique circumstances.  Obviously there needs to be room for intuition, “gut feelings,” and decisions of the heart in this situation where the scientific data will take us only so far. 

We remain hopeful that further clarification will come from future research.  The Willmar Cancer Center participates in clinical trials that will help us sort through these complex issues in oncology.

William Shimp, M.D.
Medical Oncologist