Breast Cancer: 2. A Paradigm for Solid Tumor Chemotherapy
Pp. 130-145 (16)
Pierre R. Band
In the early 1960s, breast cancer was considered to be poorly responsive to
chemotherapy. However, several agents, in particular methotrexate, vincristine, 5-
fluorouracil, cyclophosphamide, an alkylating agent synthesized in Germany, and
prednisone were found to be active in women with metastatic breast cancer. These five
drugs were then used in advanced breast cancer in a combination referred to as the
“Cooper regimen” that triggered a number of studies using quadruple and quintuple
chemotherapeutic drug combinations which induced response rates superior to therapy
with single agents. These results led to the integration of combination chemotherapy
into a combined modality approach, epitomized by modern ʻadjuvantʼ chemotherapy. A
first randomized study comparing long-term postoperative single drug chemotherapy to
a placebo led to improved survival in a subset of patients. Superior results were
subsequently achieved with postoperative combination chemotherapy. The historical
development of these approaches is described.
Breast cancer, single agent chemotherapy, combination
chemotherapy, postoperative (ʻadjuvantʼ) chemotherapy.
Faculty of Medicine, McGill University, Montreal, Quebec H3G 1Y6, Canada.