Wong Zee-Wan, Ellis Matthew J
National Cancer Centre, Singapore.
Oncology (Williston Park). 2004 Apr;18(4):411-20; discussion 421, 424, 429 passim.
For many oncologists, neoadjuvant treatment for breast cancer is synonymous with preoperative cytotoxic chemotherapy, regardless of tumor characteristics. Preoperative therapy with an endocrine agent is generally considered suitable only for the frail elderly or the medically unfit. However, favorable information regarding third-generation aromatase inhibitors in the treatment of all stages of breast cancer prompts a reconsideration of this bias. In light of the fact that neoadjuvant therapy with aromatase inhibitors is restricted to postmenopausal women with strongly estrogen-receptor-positive tumors, the assumption that neoadjuvant combination chemotherapy is more efficacious than a third-generation aromatase inhibitor can be reasonably questioned. It is particularly remarkable that the outcome of a comparison of adjuvant tamoxifen vs anastrozole (Arimidex)--the Arimidex, Tamoxifen Alone or in Combination (ATAC) trial--in more than 6,000 patients was predicted by a neoadjuvant trial that showed an efficacy advantage for a third-generation aromatase inhibitor (letrozole [Femara]) compared to tamoxifen in a sample of 337 patients after only 4 months of treatment. The potential of the neoadjuvant setting in efforts to identify new biologic agents that could build on the effectiveness of adjuvant aromatase inhibitors is therefore beginning to be appreciated. Finally, neoadjuvant therapy with an aromatase inhibitor could be considered a sensitivity test of endocrine therapy that might be incorporated into strategies to individualize treatment according to response. For this possibility to be realized, however, a better understanding of the relationship between surrogates from the neoadjuvant setting and the long-term outcome of adjuvant aromatase inhibitor therapy will have to be established through practice-setting clinical trials.
对许多肿瘤学家而言，无论肿瘤特征如何，乳腺癌的新辅助治疗等同于术前细胞毒性化疗。内分泌药物的术前治疗通常仅被认为适用于体弱的老年人或身体状况不佳者。然而，关于第三代芳香化酶抑制剂在乳腺癌各阶段治疗中的有利信息促使人们重新审视这种偏见。鉴于芳香化酶抑制剂的新辅助治疗仅限于雌激素受体强阳性的绝经后女性，新辅助联合化疗比第三代芳香化酶抑制剂更有效的假设可受到合理质疑。尤其值得注意的是，在337例患者仅治疗4个月后，一项新辅助试验显示第三代芳香化酶抑制剂（来曲唑[弗隆]）相对于他莫昔芬具有疗效优势，而该新辅助试验预测了一项针对6000多名患者的辅助他莫昔芬与阿那曲唑（瑞宁得）对比试验——阿那曲唑、他莫昔芬单药或联合应用（ATAC）试验——的结果。因此，新辅助治疗在识别可基于辅助芳香化酶抑制剂疗效的新生物制剂方面的潜力开始得到认可。最后，芳香化酶抑制剂的新辅助治疗可被视为内分泌治疗的敏感性试验，这可能会被纳入根据反应个体化治疗的策略中。然而，要实现这一可能性，必须通过实际临床研究更好地了解新辅助治疗替代指标与辅助芳香化酶抑制剂治疗长期结果之间的关系。
