Carlson Robert W, Henderson I Craig
Department of Medicine, Stanford University, Palo Alto, CA 94304, USA.
Breast Cancer Res Treat. 2003;80 Suppl 1:S19-26; discussion S27-8. doi: 10.1023/a:1025459232293.
The use of adjuvant endocrine therapy in the treatment of hormone receptor-positive, early breast cancer has become important in both pre- and postmenopausal women. Tamoxifen has been the principal adjuvant hormonal therapy in pre- and postmenopausal women with hormone receptor-positive breast cancer for nearly 20 years. Recent data in premenopausal women suggest benefit from ovarian ablation with or without tamoxifen. Early results from the 'Arimidex', Tamoxifen, Alone or in Combination (ATAC) trial have demonstrated that the third-generation, selective aromatase inhibitor (AI) anastrozole ('Arimidex') is a suitable alternative adjuvant therapy for postmenopausal women with hormone receptor-positive disease. After recurrence or relapse on adjuvant endocrine therapy, responses to the sequential use of additional endocrine agents are common. The increase in the number of options now available for adjuvant therapy will have important implications for the selection of the optimal sequence of endocrine agents in the treatment of recurrent breast cancer. Menopausal status is an important factor in determining the endocrine therapy that a patient receives. For premenopausal women, tamoxifen and/or a luteinizing hormone-releasing hormone agonist such as goserelin ('Zoladex') are both options for adjuvant endocrine treatment. After progression on adjuvant and first-line tamoxifen, ovarian ablation is an appropriate second-line therapy. For premenopausal women who have undergone ovarian ablation, the use of third-line therapy with an AI becomes possible. For postmenopausal women, a wide choice of endocrine treatment options is available and an optimal sequence has yet to be determined. Options for first-line therapy of metastatic disease include an AI for women who have received adjuvant tamoxifen or tamoxifen for patients who have received adjuvant anastrozole. In addition, data suggest that fulvestrant ('Faslodex'), a novel estrogen receptor (ER) antagonist that downregulates the ER protein and has no known agonist effects, is a promising therapeutic option that has shown efficacy in the treatment of postmenopausal women with advanced breast cancer. Other agents that may be used in the sequence include the steroidal AI exemestane and the progestin megestrol acetate. The widening range of adjuvant endocrine options therefore represents an opportunity to prolong patient benefits in the treatment of hormone receptor-positive breast cancer, and will require the further refinement of the optimal sequence of endocrine agents for the treatment of recurrent breast cancer.
辅助内分泌治疗在激素受体阳性早期乳腺癌的治疗中，对绝经前和绝经后女性均已变得至关重要。在近20年里，他莫昔芬一直是激素受体阳性乳腺癌绝经前和绝经后女性的主要辅助激素治疗药物。绝经前女性的最新数据表明，无论是否联合他莫昔芬，卵巢去势均有益处。“瑞宁得”、他莫昔芬单独或联合使用（ATAC）试验的早期结果显示，第三代选择性芳香化酶抑制剂（AI）阿那曲唑（“瑞宁得”）是激素受体阳性疾病绝经后女性合适的替代辅助治疗药物。辅助内分泌治疗复发或病情进展后，序贯使用其他内分泌药物常见有效。目前辅助治疗可用方案数量的增加，对于复发性乳腺癌内分泌药物最佳使用顺序的选择将具有重要意义。绝经状态是决定患者接受何种内分泌治疗的一个重要因素。对于绝经前女性，他莫昔芬和/或促黄体生成素释放激素激动剂如戈舍瑞林（“诺雷德”）都是辅助内分泌治疗的选择。辅助及一线使用他莫昔芬病情进展后，卵巢去势是合适的二线治疗方法。对于已接受卵巢去势的绝经前女性，使用AI进行三线治疗成为可能。对于绝经后女性，有多种内分泌治疗选择，最佳顺序尚未确定。转移性疾病一线治疗的选择包括，对于接受过辅助他莫昔芬治疗的女性使用AI，或对于接受过辅助阿那曲唑治疗的患者使用他莫昔芬。此外，数据表明，氟维司群（“芙仕得”），一种新型雌激素受体（ER）拮抗剂，可下调ER蛋白且无已知激动剂作用，是一种有前景的治疗选择，已显示出对绝经后晚期乳腺癌女性的治疗效果。该治疗顺序中可能使用的其他药物包括甾体AI依西美坦和孕激素醋酸甲地孕酮。因此，辅助内分泌治疗选择范围的扩大，为延长激素受体阳性乳腺癌患者的获益提供了机会，并且需要进一步优化复发性乳腺癌内分泌药物的最佳使用顺序。
