© 2001 by Oxford University Press
Journal of the National Cancer Institute Monographs, No. 30, 16,
2001
© 2001 Oxford University Press
Adjuvant Therapy for Breast Cancer: Current Controversies and Future Prospects
Correspondence to: William C. Wood, M.D., Department of Surgery, Emory University School of Medicine, Atlanta, GA 30322
Carcinoma of the breast remains the most common cancer in women in the United States. It is exceeded only by lung cancer as a cause of cancer death in women. In 1980, the National Institutes of Health (Bethesda, MD) held a consensus development conference that addressed the efficacy of adjuvant chemotherapy in breast cancer (1). In 1985, another conference was held that addressed the survival benefit associated both with adjuvant chemotherapy and with adjuvant hormonal therapy for women with primary breast cancer (2). In 1990, at the time of the last consensus development conference (3), breast cancer appeared to be increasing modestly nationally, partly because of increased detection of early breast cancer by the growing use of screening mammography. The mortality rate in 1990 appeared to be absolutely flat. The consensus conference held 10 years ago concluded that breast conservation therapy was appropriate for the management of primary breast cancer. It further concluded that adjuvant systemic therapy provided benefit to women regardless of lymph node status and that it should be recommended based on risk and benefit as judged by a complex of prognostic factors, including size of the primary tumor and lymph node status. These conclusions were based on large, randomized clinical trials. Every major advance in the management of breast cancer has emerged from clinical trials. Without continued basic research in breast cancer, there will be no future for clinical trials.
At the present time, breast cancer in the United States appears to be at a plateau of frequency when it is age adjusted. The encouraging news is that mortality from breast cancer in this country and in many European countries has been falling for the last 8 years, which probably reflects the benefit of both adjuvant tamoxifen and screening mammography. The last decade has brought major clinical trials addressing the significance of duration in the administration of adjuvant tamoxifen, the role of anthacyclines in adjuvant chemotherapy, the role of taxanes, the significance of chemotherapy dose and intensity, the significance of chemotherapy duration, and predictive factors for response to adjuvant therapy. These clinical trials provide the datasets that enable this conference to address these current controversies.
The questions that have been chosen for the panel to address meet two criteria: 1) They are of crucial interest to breast cancer patients and their healthcare team, and 2) a body of scientific evidence exists to allow an informed consensus.
Several questions were debated and felt to be important future prospects presently not ready for consensus evaluation. One was the mapping and evaluation of sentinel lymph nodes to tailor lymph node staging. Numerous questions are under investigation regarding the type of sentinel lymph node mapping best used, the false-negative rate to be expected, and its relationship to experience. Clinical trials have already demonstrated the role of surgical experience, both as the percentage of sentinel lymph nodes identified and the false-negative rate. Large randomized clinical trials are under way to address these questions, as well as the optimal site of tracer injection within the breast and the degree to which sentinel lymph nodes are specific to the area of the breast in which the primary tumor arises. Another question involves the role of immunohistochemical evaluation of bone marrow biopsies. Which antibody combination to use and what patients will have an advantage by such information and whether such information will be predictive of therapeutic response or only prognostic are still under evaluation. Either of these assays can be overinterpreted by detecting molecular evidence of tumor cells that are not micrometastases but simply circulating in the process of apoptosis or immune destruction. These are important issues being addressed with current clinical trials.
Herceptin is a potent new agent in the treatment of breast cancer. Its role as a component of adjuvant systemic therapy is being evaluated in large randomized clinical trials by the National Institutes of Health Breast Intergroup, the National Surgical Adjuvant Breast and Bowel Project, the Breast Cancer Treatment Research Group, and the Breast International Group. The significance of bisphosphonates as a component of adjuvant therapy is being studied. The delayed use of adjuvant hormonal therapy or chemotherapy and the use of techniques of maintenance therapy as a component of adjuvant therapy are all undergoing clinical trial at this time. Tailored therapy for locally advanced breast cancer is being addressed in numerous clinics and cooperative groups. The treatment of in situ carcinoma and the prophylaxis of persons at high risk are continuing to evolve and may deserve consideration by consensus panels in the future. Other future prospects include the significance of antiangiogenesis therapies as a component of adjuvant therapy, the use of vaccines, tailored small molecules, antisense constructs, and other therapies arising from the rapid advances of tumor biology and molecular genetics. None of these was judged by the planning committee to have sufficient evidence from mature trials for consensus development. Each is worthy of ongoing research.
REFERENCES
1 Adjuvant chemotherapy of breast cancer. NIH Consensus Development Conference Summary. Vol 3, No 3, 1980.
2
National Institutes of Health Consensus Development Conference Statement: adjuvant chemotherapy for breast cancer. September 9–11, 1985. Cancer J Clin 1986;36:42.
3 Consensus statement: treatment of early-stage breast cancer. J Natl Cancer Inst Monogr 1992;11:1.
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