High-Dose Chemotherapy for Breast Cancer: No Better Than Traditional Chemotherapy
There are four standard types of treatment for ]]>breast cancer]]> : ]]>surgery]]> , ]]>radiation therapy]]> , ]]>chemotherapy]]> , and hormone therapy. The type chosen in each case depends on the stage of the cancer and other factors that vary with each patient. Chemotherapy uses medications to stop the growth of cancer cells by killing the cells or stopping them from dividing. It may be used alone or with other types of treatment. Scientific knowledge about the effectiveness of chemotherapy comes only from careful clinical trials that compare different combinations and dosages of anti-cancer medications. In treating tumors of all sorts, effectiveness sometimes increases with higher drug dosages, but side effects are often significantly worse. A current focus in much oncology research is to identify treatments which maximize effectiveness and minimize complications.
Chemotherapy treatment for breast cancer began in the 1970s following the pioneering studies of the National Surgical Adjuvant Breast and Bowel Project and similar work by Italian scientists. Chemotherapy has been proven beneficial, but not often curative. For women at high risk for breast cancer relapse after surgery, scientists tried especially high doses of chemotherapy in hopes of achieving higher effectiveness than was possible from conventional, low-dose chemotherapy. This high dosage treatment is so strong that follow-up ]]>blood cell transplants]]> are required to replenish bone marrow damaged during the treatment. In total, it’s estimated that over 15,000 women have had high-dose chemotherapy and blood cell transplants for the treatment of breast cancer.
Initial reports from the early 1990s suggested that the high-dose treatment was producing better results than conventional chemotherapy. Because of publicity given to these preliminary results, demand for high-dose treatment by patients and advocates increased. Some state legislatures mandated that insurance companies pay for this treatment.
By the late 1990s it became clear that randomized clinical trials, the most scientifically rigorous types of studies, were needed to prove whether the risks of high-dose chemotherapy were balanced by better results. This research was important because the high-dose chemotherapy was more difficult and toxic, thus causing worse side effects. It was also more expensive. In addition, researchers wanted to determine whether the results varied among patients by factors, such as the stage of the cancer.
Results From Clinical Trials
In early 2000, results from the first clinical trials showed that high-dose chemotherapy was no more effective than standard chemotherapy for women with advanced or high-risk breast cancer, and that side effects were more common. The findings were published in the April 13, 2000 issue of the New England Journal of Medicine and the February 2, 2000 issue of the Journal of the National Cancer Institute. Both studies concluded that high-dose chemotherapy was not to be generally recommended for patients with high-risk breast cancer.
Because of these findings, the American Society of Clinical Oncology (ASCO) and editorials in the New England Journal of Medicine and The Lancet recommended that women receive the high-dose treatment only if they were part of a “high-quality” clinical trial (a carefully monitored research study). Aetna/US Healthcare, one of the largest health insurers in the US, said that it would now only pay for high-dose chemotherapy for patients in federally sponsored clinical trials, although it had been paying for the costs for women who were not in clinical trials.
Results from more recent published studies have provided further support for the use of conventional rather than high-dose chemotherapy in most breast cancer patients. A study in the Journal of the National Cancer Institute on July 21, 2004 reported that “high-dose therapy is not superior to conventional chemotherapy in patients with breast cancer who have multiple involved lymph nodes.” Two studies published in the July 3, 2003 issue of the New England Journal of Medicine also showed that there was no significant difference in the length of life (five-year survival rate) between the two treatments.
There was, however, one area where both of the 2003 studies found a possible benefit from the high-dose therapy. In one subgroup of patients (women with stage II or III breast cancer and 10 or more cancerous lymph nodes), those on the high-dose chemotherapy had a reduced risk of relapse and a longer time before recurrence of breast cancer compared to those on the conventional treatment. However, this difference did not lead to an overall increase in length of life, partly because the blood cell transplantation performed with the high-dose chemotherapy caused complications that contributed to a decrease in length of life. More recent studies from Duke University show some benefit of high-dose treatment among very high risk women whose tumors are not sensitive to hormones.
Current Recommendations and Questions for Further Research
At this time, conventional rather than high-dose chemotherapy remains the standard form of chemotherapy for women with high-risk breast cancer since the high-dose therapy has not been proven more effective in lengthening life. However, further research in carefully controlled clinical trials is needed to determine whether high-dose chemotherapy may be more effective in some selected women and whether that benefit is worth the extra toxicity and cost of the treatment. Also to be further investigated is whether improvements in the blood cell transplantation strategies may eventually increase length of life in patients who receive the high-dose chemotherapy.
American Cancer Society
National Breast Cancer Coalition
National Cancer Institute
Breast cancer (PDQ®): treatment. Treatment option overview. National Cancer Institute website. Available at: http://www.cancer.gov/cancertopics/pdq/treatment/breast/Patient/page5 . Accessed August 10, 2004.
High-dose chemotherapy for breast cancer: Clinical trials overview. National Cancer Institute website. Available at: http://www.cancer.gov/clinicaltrials/developments/high-dose-chemo-overview0401 . Accessed August 10, 2004.
High-dose chemotherapy for breast cancer: History. National Cancer Institute website. Available at: http://www.cancer.gov/clinicaltrials/developments/high-dose-chemo-history0501 . Accessed August 10, 2004.
High-dose chemotherapy with stem cell transplantation: Still no clear benefit. National Cancer Institute website. Available at: http://www.cancer.gov/clinicaltrials/results/high-dose-chemo0703 . Accessed August 10, 2004.
Hortobagyi GN, Buzdar AU, Theriault RL, et al. Randomized trial of high-dose chemotherapy and blood cell autografts for high-risk primary breast carcinoma. J Natl Cancer Inst. 2000;92(3): 225-233.
Leonard R, Lind M, Twelves C, et al. Conventional adjuvant chemotherapy versus single-cycle, autograft-supported, high-dose, late-intensification chemotherapy in high-risk breast cancer patients: A randomized trial. J Natl Cancer Inst. 2004;96(14):1076-1083.
Rodenhuis S, Bontenbal M, Beex L, et al. High-dose chemotherapy with hematopoietic stem-cell rescue for high-risk breast cancer. N Eng J of Med. 2003;349(1):7-16.
Stadtmauer E, O’Neill A, Goldstein L, et al. Conventional-dose chemotherapy compared with high-dose chemotherapy plus autologous hematopoietic stem-cell transplantation for metastatic breast cancer. N Eng J of Med. 2000;342(15):1069–1076.
Tallman MS, Gray, R, Robert NJ, et al. Conventional adjuvant chemotherapy with or without high-dose chemotherapy and autologous stem-cell transplantation in high-risk breast cancer. N Eng J of Med. 2003;349(1):17–26.
Last reviewed July 2008 by ]]>Igor Puzanov, MD]]>
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