In the 1950s and 1960s, the treatment of metastatic breast cancer in women consisted of hormonal ablative or additive procedures. However, no tests were available to predict patients’ response; as a result, about 60% to 70% of the women who underwent these endocrine procedures failed to respond. The discovery of the estrogen receptor enabled clinicians to select those women with breast cancer most likely to respond to hormonal procedures. Response to endocrine therapy occurred in about 60% of women with estrogen receptor rich tumors, as opposed to 8% in women with estrogen receptor poor tumors. Of added importance, assay of the estrogen receptor in the primary breast tumor was found to be predictive of response to endocrine therapy in women who subsequently developed disease recurrence. Tamoxifen, an anti-estrogenic compound synthesized in Great Britain, inhibits the binding of estrogen to the estrogen receptor. Tamoxifen underwent extensive fundamental and clinical investigations and became the standard form of endocrine therapy for breast cancer for over a quarter of a century.