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.
Keywords: Breast cancer, single agent chemotherapy, combination
chemotherapy, postoperative (ʻadjuvantʼ) chemotherapy.