New studies published recently cast doubts on the effectiveness of high-dose chemotherapy plus bone marrow stem cell transplantation for the treatment of breast cancer.

Women with primary breast cancer and local lymph node metastasis have a poor prognosis. Even with the aggressive treatments involving surgical removal of the tumors and post-operative (adjuvant) chemotherapies, only 20 to 30 percent of these patients are likely to survive for five years or longer. Doctors and researchers are actively searching for better treatment methods. In the early 1980s, interest in using bone marrow hematopoietic stem cell transplantation bone marrow or well defined stem cells was significantly elevated among patients and physicians to treat cancers, other than malignant lymphoma and leukemia. Breast cancer became the most common indication for using such transplantations. Then a combination strategy of using chemotherapy and stem cell transplantation was developed. The idea was to use high-dose anti-cancer drugs (usually 2-20 times higher than standard doses) to kill as many breast cancer cells as possible. These high doses also kill bone marrow cells, leaving patients at risk of anemia and infections. To avoid this, patients will receive a transplant of bone marrow stem cells collected either from themselves or from the donors.

Several groups reported in the mid-1990s that high-dose chemotherapy with autologous hematopoietic stem-cell transplantation was more effective than conventional chemotherapy. In their studies, the three-year disease-free survival rate was approximately 65-70 percent with the new regimen. Encouraged by these promising results, autologous hematopoietic stem cell transplantation and high-dose chemotherapy became a popular treatment for high-risk patients. Despite this, there was considerable debate over the quality of the published data and the lack of further randomized trials to prove the value of this expensive and debilitating procedure. Notably, the mortality rate from the procedure itself initially ran as high as 10-20 percent. Although this rate had been gradually reduced later on, it is still significant.

Five years ago, researchers found that the majority of the original reported results were not repeatable. Results from the new studies indicated that there was actually no benefit for the patients with the high-dose regimen. It raised a question of whether to continue this treatment. Clearly, a large-size, prospective and controlled study was required to ascertain the efficacy of this treatment.

Now two large-size studies, conducted by an American group and a Dutch group, respectively, were reported. While the Dutch group’s study (885 patients) reached somewhat inconclusive conclusions, the results from the United States study (which involved 540 patients) specifically pointed out that high-dose chemotherapy followed by a bone marrow transplant is not an effective way to treat breast cancer.

There are clear conflicts between the results from current studies and those reported in the early 1990s. The results from the earlier studies may have been skewed by the relatively small number of patients used in these studies, as well as by a bias on the selection of patients.

Despite the negative conclusions of the two current studies concerning the rates of recurrence, disease-free survival, and overall survival after high-dose chemotherapy, there maybe subgroups of patients who can obtain a benefit from high-dose chemotherapy. For patients with HER-2/neu-negative tumors, the relapse-free survival was significantly longer after high-dose therapy than after conventional therapy. However, identifying such subgroups will require a very large number of patients.

[Discovery Medicine, 2(17):28, 2003]