Current and future directions in medical therapy for breast carcinoma: endocrine treatment

Endocrine therapy remains a mainstay of treatment for breast carcinoma in both adjuvant and metastatic settings. The choice of endocrine therapy is guided by the presence and degree of expression of estrogen receptor (ER) and progesterone receptor (PgR) as well as by clinical parameters. Adjuvant tamoxifen (TAM) given for 5 years is accepted standard therapy for postmenopausal ER and/or PgR positive (+ve) women. In premenopausal women, 5 years of TAM given alone has similar effects, but is used less frequently because chemotherapy has been regarded as a standard even in ER and PgR +ve women. Recent literature has demonstrated the equivalence or superiority of (Zoladex [ZOL], Zeneca Pharmaceuticals, Wilmington, DE) goserelin acetate plus TAM to cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) chemotherapy in premenopausal ER and PgR +ve women. This, together with older data showing equivalence or superiority of ovarian ablation (OA) to CMF chemotherapy in the same setting, as well as accumulating data suggesting benefit from the addition of ZOL, OA, and/or TAM to chemotherapy in the premenopausal adjuvant setting, has raised issues regarding whether ZOL, OA, and/or TAM can substitute for chemotherapy or should always be added to it for premenopausal receptor +ve women. In the metastatic setting, the second-generation aromatase inhibitors (AI) clearly have moved into position as second-line therapy after TAM. Recent data have shown equivalence and perhaps some superiority to TAM by at least one AI (anastrazole [AN]) in first-line metastatic treatment. The results of adjuvant studies comparing TAM, AN, and TAM + AN in the adjuvant setting will be awaited with great interest. In the interim, the development of other SERMS (raloxifene, EM 850) and of pure antiestrogens may provide new and exciting approaches in the metastatic, adjuvant, and preventive settings.