The treatment of breast cancer, which is the leading cause of cancer deaths among West German women, includes both cytotoxic and hormonal therapy. Approximately one half of breast cancers possess estrogen receptors, and of these tumors about two-thirds are initially responsive to the better tolerated hormonal treatments (11). However, the first good results are usually followed by a regrowth of the patient’s tumor which is then resistant to further hormonal therapy. The clinician must turn to an aggressive regime of cytotoxic drugs, with toxic side effects feared by most patients. The idea behind the present drug-design approach was to begin treatment of estrogen receptor-positive (ER + ) tumors with well-tolerated cytotoxic therapy. This therapy would take advantage of the unique presence of estrogen receptors in the tumor cells. By coupling a DNA-reactive cytotoxin to a molecule with affinity for the estrogen receptor, it was thought that the cytotoxin would be selectively enriched in tumor cells positive for the estrogen receptor (7). A degree of sensitivity might also be gained if the estrogen receptor delivered the reactive cytotoxin to a critical region of DNA. Thus, with these added degrees of selectivity and sensitivity, cytotoxic chemotherapy might be achieved with fewer side effects. Such a drug might also be active against those tumors which are resistant to hormone therapy although the biopsies are positive for estrogen receptors. The strategy of linking the cytotoxic cisplatin (1) to either a nonsteroidal estrogen or antiestrogen appeared promising. The chemistry and pharmacology of cisplatin has been reviewed (2). Briefly, the reaction of cisplatin with DNA, specifically the intrastrand linking of adjacent guanines, is presumed to be the mechanism responsible for antineoplastic activity. Chemotherapy with cisplatin is well established in the cancer wards with a spectrum of activity that includes testicular, ovarian, endometrial, bladder, and head and neck cancer (14), but not breast cancer (5). One aim of the project was therefore to broaden the activity of cisplatin to include breast cancer. Considering the estrogen receptor-binding portion of the molecule, nonsteroidal estrogens and antiestrogens would appear to offer more synthetic possibilities for developing structure-activity relationships than steroidal estrogens.