Adjuvant Therapy of Breast Cancer

Breast cancer is the most common malignancy among women in the United States and is second only to lung cancer as the most common cause of cancer-related mortality. In 2000, it is estimated that 182,800 new cases of invasive breast cancer will be diagnosed, as well as 42,600 new cases of ductal carcinoma in situ (DCIS). Although mortality rates from breast cancer declined by approximately 1.8% per year between 1990 and 1996, 40,800 women are still expected to die from breast cancer in 2000. Widespread screening and improvements in treatment, particularly with the use of post-operative adjuvant chemotherapy and hormonal therapy, have contributed to this declining mortality.

In women with "early-stage" breast cancer, all detectable disease is limited to the breast and, in women with lymph node-positive disease, to the axillary lymph nodes. Advances in surgery have provided local control with goals towards removing less tissue, and patients are now offered several surgical options including modified radical mastectomy, lumpectomy with axillary lymph node dissection, and lumpectomy with sentinel lymph node mapping and selective lymphadenectomy.

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Adjuvant radiation therapy has reduced the incidence of local recurrence after breast-conservation therapy. Despite adequate local control, undetected deposits of micrometastatic disease will remain in some patients, and if left untreated, may develop into recurrent disease.

In the late 19^th century, Halsted proposed the theory of the orderly spread of cancer, which traveled from the breast through the axillary lymph node "filter" to distant metastatic sites. It is now thought that metastases can occur much earlier in the natural history of the disease.

Therefore, the treatment of breast cancer requires a "systemic" approach with the use of therapies that will treat the "distant" microscopic disease that has already escaped the breast and lymph nodes by the time of initial surgery. Systemic postoperative treatment, referred to as "adjuvant therapy," has been the focus of numerous clinical trials over the past 25 years, representing an effort to reduce this risk of recurrence in these women.

The Early Breast Cancer Trialists' Collaborative Group (EBCTCG) was formed in 1985 to perform systematic overviews (meta-analyses) of all of the randomized trials of treatment of early-stage (resectable) breast cancer including chemotherapy and hormonal therapy. The EBCTCG continues to meet every 5 years to update the worldwide prospective experience with adjuvant therapy. The results of the most recent 1995 overview analysis were published in 1998. Because of the large number of women included in these trials as well as the long duration of follow-up, these overviews provide a powerful tool with which to analyze the worldwide randomized data.

The results of these analyses will be the focus of this review, as they provide the foundation on which medical oncologists base their selection of adjuvant therapy.