According to the results of a Phase III clinical trial published in the Journal of the National Cancer Institute, the addition of chemotherapy to tamoxifen for the adjuvant treatment of early breast cancer produces modest but sustained improvements in overall survival. A second Phase III trial, published in the same issue, did not find an overall benefit of adding ovarian suppression to treatment with tamoxifen among premenopausal breast cancer patients.
Early-stage breast cancer refers to cancer that is either confined to the breast or that has not spread beyond the axillary (underarm) lymph nodes. While some early-stage breast cancers are effectively treated with surgery and radiation therapy alone, others (particularly those that have spread to nearby lymph nodes) also require systemic treatments such as chemotherapy, hormonal therapy, or targeted therapy.
To evaluate whether combinations of different types of adjuvant therapy are more effective than single modality therapy, researchers with the Adjuvant Breast Cancer (ABC) Trials group conducted two Phase III clinical trials. Both trials began in the early 1990s and completed subject enrollment in 2000.
The first trial evaluated the effect of adding combination chemotherapy (most commonly consisting of cyclophosphamide, methotrexate, and 5-fluourouracil) to treatment with tamoxifen. The study enrolled 1,991 patients between the ages of 26 and 81 years. All women were receiving five years of tamoxifen, with or without ovarian suppression, for the adjuvant treatment of early breast cancer. Half the patients received chemotherapy and half did not.
- The addition of chemotherapy reduced the risk of death by 17%.
- There was a suggestion that the benefit of chemotherapy may be greatest in younger women (under the age of 50) and in premenopausal women who did not undergo ovarian suppression.
The second trial evaluated the effect of adding ovarian suppression to tamoxifen for the adjuvant treatment of premenopausal breast cancer. The study enrolled 2,144 women, all of whom received tamoxifen with or without chemotherapy. Half the women were assigned to undergo ovarian suppression (either surgical removal of the ovaries, radiation to the ovaries, or use of drugs to suppress ovarian function) and half were not.
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- Overall, the addition of ovarian suppression to tamoxifen did not improve relapse-free or overall survival.
- The researchers note that further evaluation of ovarian suppression is warranted in women under the age of 40 with estrogen receptor-positive tumors, particularly those not receiving chemotherapy.
An important limitation of both of these trials is that they had limited information about the estrogen receptor status of the breast cancers. The benefits of each of the treatments evaluated are likely to vary by estrogen receptor status. The benefits of adding chemotherapy to tamoxifen are likely to vary by other tumor characteristics as well. Women who have been diagnosed with early breast cancer may wish to talk with their physician about the specific characteristics of their cancer, and the need for, and optimal approach to, adjuvant hormonal therapy, chemotherapy, and/or targeted therapy.
The Adjuvant Breast Cancer Trials Collaborative Group. Polychemotherapy for early breast cancer: results from the International Adjuvant Breast Cancer Chemotherapy Randomized Trial. Journal of the National Cancer Institute. 2007;99:506-15.
The Adjuvant Breast Cancer Trials Collaborative Group. Ovarian ablation or suppression in premenopausal early breast cancer: results from the International Adjuvant Breast Cancer Ovarian Ablation or Suppression Randomized Trial. Journal of the National Cancer Institute. 2007;99:516-25.
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