The role of chemotherapy in breast cancer

Abstract

Attitudes over the contribution of chemotherapy in the treatment of breast cancer have fluctuated from extreme optimism to pessimism and back during the past 20 years. XJost of the lability demonstrated by the medical community (and the lay public) has been based on real accomplishments achieved bv chemotherapy in controlled clinical trials that have then been extended to unreal expectations. In order to understand the role and current limitations of chemotherapy today it is imperative that the focus be placed on sound clinical trials of the past several years. Breast cancer displays an intermediate range of sensitivity to a wide variety of antineoplastic agents. nctivity of most of the drugs currently used in breast cancer management was established in the 1960’s. Until recently, few new drugs have demonstrated sufficient activity to supnlement or compete with these agents. The nitrosoureas, podophyllotoxins and cisplatin have little activity in breast cancer despite a broad spectrum of anti-neoplastic effects in other human malignancies. However, other investigational drugs such as dibromodulcitol and the anthracenes have more recently shown promise. A major new development of the late ‘60’s and early ‘70’s was combination chemotherapy for treatment of breast cancer. Randomized studies of single agent versus drug combinations have demonstrated superior response rates for the drug combinations, but not all patient subgroups have benefitted equally and not all the benefit has transposed into a survival advantage. Because data on the impact of treatment of advanced breast cancer require years to mature, some of the population subgroup differences in response to combination chemotherapy were not apparent in preliminary analyses and have not been adequately pursued in subsequent investigations. Subsequent trials have generally failed to demonstrate major therapeutic gain from the addition of adriamycin to drug combinations. Nevertheless, evidence from randomized studies again suggests benefit in distinct population subgroups. This evidence may be important in establishing new directions in advanced breast cancer treatment as well as in supplying an understanding of adjuvant therapy. Impetus for adjuvant therapy of breast cancer originated with the attempt to address the problem of perioperative dissemination of cancer cells. This concept was subsequently rejected in popularizing the idea that breast cancer is a . systemic disease from its onset. Several randomized trials have addressed these issues and more recent studies are evaluating the addition of hormones and the issue of chemotherapy timing. Again population subsets emerge with definite survival advantage from various treatment regimens. However, if it takes years to achieve interpretable results in advanced breast cancer, it takes a decade or more to gain information about early breast cancer. It is clear that not all population subgroups benefit equally from the same treatment, making it imperative that different treatment approaches be compared in an investigative clinical trial setting. Finally, the interaction of chemotherapy with other modalities, and especially radiation therapy, has both produced the promise of improved durability of disease control, but also a need to understand complicating treatment interactions. Attention to details on the type of drug used with radiation therapy and the possibility of additive toxicities, especially skin and hematologic, are important in avoiding potentially harmful compromises in treatment. These considerations require that we all have a basic understanding of the biologic principles and limiting factors of each of our therapeutic tools.