From the Executive Director: The Challenges of Changing Breast Cancer Treatments

by Barbara A. Brenner

One of BCA’s primary objectives is to make sure that everyone who needs breast cancer treatment has access to the most effective and least toxic therapies available. As we learn more about what treatments work for specific patients, it seems that many women and men diagnosed with breast cancer should soon be able to avoid some of the most toxic treatments that have been developed. But a double standard seems to be operating that means far too many people are getting treatments that are not only very aggressive, but are also unnecessary and of no benefit. The double standard has to do with how little evidence is needed to bring a new treatment into regular use versus how much evidence is needed to stop a treatment once it’s been shown to be ineffective in a group of patients.

There are two recent good examples of how the rush to add new treatments for breast cancer contrasts with the delay in removing drugs from the list of therapy options. One example is anthracyclines and the other is Taxol.

The most commonly used anthracyline treatment for breast cancer is Adriamycin (generic name doxorubicin). Because the drug is both very toxic and red in color, it is referred to in the oncology community as the “Red Death.” When I was first treated for breast cancer in the early 1990s, the drug was approved only for use in patients with metastatic disease but was quickly moving into the adjuvant treatment setting. Today, nearly everyone for whom chemotherapy is recommended is treated with Adriamycin. The drug has many serious side effects, including the risk of permanent heart damage.

For several years, Dennis Slamon, the person credited with the development of Herceptin, has been reporting on research that shows that women whose breast tumors overexpress the Her2/neu protein (HER2-positive) benefit from anthracyclines, but those whose breast tumors are HER2-negative do not. As Ralph Moss reported in his Cancer Decisions Newsletter in July 2007, a number of studies now support this conclusion and lead inevitably to the observation that women who do not overexpress Her2/neu (and an additional gene known as Topoll-2–topoisomerase II alpha) should not receive anthracyline treatment, because they won’t derive any benefit from the drug.

Yet doctors, including many who attended the San Antonio Breast Cancer Symposium in December, are not ready to drop this very aggressive treatment from cases where it clearly doesn’t seem to work (See my SABCS Reflections).

The Taxol (paclitaxel) story is quite similar. In 1998, as a result of a single study of Taxol in node-positive breast cancer patients that showed a small improvement in overall survival for patients treated with Taxol, treatment changed overnight. (For more information, read “Hope and Hype Dominate ASCO Meeting,” in the BCA Source #49, August/September 1998.) Women who before 1998 would have received a two-combination chemotherapy regimen of Adriamycin and Cytoxan (cyclophosphamide) began receiving these two drugs followed by Taxol. Many people experience one of the side effects of this systemic chemotherapy drug, peripheral neuropathy—nerve damage to the feet and hands.

In a study published in the October 2007 edition of the New England Journal of Medicine, Daniel Hayes reported that women whose breast cancers were estrogen-receptor-positive and HER2-negative gained no benefit from the addition of Taxol to their chemotherapy treatment. And, while it took only one study to add Taxol to the treatment regimen, both Hayes and others urged against stopping the prescription of Taxol on the basis of this study alone.

Why does it take so little to add an aggressive therapy to treatment, but so much to remove one when evidence shows that it’s not working? I think there are two reasons. One is that U.S. doctors in particular have been trained (as have many patients) to believe that hitting cancer as quickly and with as much treatment as possible is going to be more successful in saving lives than a less aggressive approach. Given this training, doctors probably fear giving up on a treatment that they think might help some patients. Making a mistake could have big consequences if it turns out that the indications for nontreatment are wrong, or if a patient has a recurrence that might not have happened with treatment and sues for malpractice.

The other is that there is a huge investment in these drugs, and a lot of money being made in producing and administering them. Financial interests stand in the way of many changes. They create a large ship that is very hard to turn in a new direction.

But patients who are well informed can demand that treatments change as new information becomes available about who benefits and who doesn’t. It shouldn’t be up to us, but it is.

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