• If patients respond to initial hormonal treatment and then relapse, other forms of hormonal therapy are used. • If major internal organs such as the liver are involved and hormone receptors are negative, chemotherapy is usually given. Standard combinations include CMF, CAF and CMFP (see "Stage IIIA" and "Stage IV" ). Cyclophosphamide + doxorubicin appears to produce similar results but has been studied less extensively. Other combinations include mitomycin-C + vinblastine as well as vinblastine + doxorubicin + thiotepa + fluoxymesterone (VATH). Taxol may be of value in patients who fail to respond to doxorubicin. • Combination chemotherapy with or without hormone management is given to patients who recur or who no longer respond to hormonal manipulation. Investigational • If there is major organ involvement and negative hormone receptors, clinical trials of combination chemotherapy, newly developed chemotherapy agents and biologic treatment should be considered ( see Investigational Anticancer Drugs ). • Leuprolide is also undergoing clinical trial as a method of hormonal manipulation. This suppresses the ovaries similar to removing them (a medical oopharectomy). • Examples of drugs in clinical trial are anthrapyrazoles, taxotere, topotecan, vinorelbine and monoclonal antibodies.