Markopoulos Christos
Athens Medical School, University of Athens, GR-11521 Athens, Greece.
Surg Oncol. 2008 Aug;17(2):113-28. doi: 10.1016/j.suronc.2007.11.006. Epub 2008 Jan 4.
Neoadjuvant therapy improves patient outcomes substantially by increasing the rate of breast-conserving surgery. Following primary surgery, women with hormone-sensitive early breast cancer remain at risk for loco-regional and systemic recurrence. The most common relapse event, distant metastases, is associated with the poorest outcomes. As a neoadjuvant therapy, anastrozole, letrozole, and exemestane have been investigated in phase 3 studies and have shown efficacy in this setting. All three aromatase inhibitors (AIs) significantly improved the rate of breast-conserving surgery. As initial adjuvant therapy, the third-generation AIs anastrozole and letrozole more effectively reduce recurrence risk compared with tamoxifen following surgery, especially in the first 2 years, when the risk is greatest. Tamoxifen, once the standard initial therapy, is associated with improved disease-free survival but may be more effective at reducing loco-regional recurrence than distant metastases. Initial adjuvant letrozole therapy has also shown a pronounced reduction in the risk of distant metastases early on in the course of therapy. If AIs are not used upfront, sequential use of exemestane or anastrozole following tamoxifen provides greater protection against relapse than continuing on tamoxifen. Side effects associated with estrogen deprivation of AIs are less serious than those of tamoxifen and are easily managed. Various molecular markers are under study as surrogates to predict response to neoadjuvant therapy, which may in turn predict responsiveness to adjuvant therapy. Surgeons treating breast cancer patients and prescribing endocrine therapy should be aware of all treatment strategies, including neoadjuvant and adjuvant hormonal therapy, and inform their patients of the benefits and the potential side effects. Early and long-term-risk reduction with AI treatment should be discussed with patients, as should the management of common AI-associated adverse events.
新辅助治疗通过提高保乳手术率显著改善了患者的治疗效果。在初次手术后，激素敏感型早期乳腺癌女性仍有局部区域和全身复发的风险。最常见的复发事件——远处转移，与最差的治疗结果相关。作为新辅助治疗，阿那曲唑、来曲唑和依西美坦已在3期研究中进行了调查，并在这种情况下显示出疗效。所有三种芳香化酶抑制剂（AIs）均显著提高了保乳手术率。作为初始辅助治疗，与他莫昔芬相比，第三代AIs阿那曲唑和来曲唑在术后能更有效地降低复发风险，尤其是在风险最大的前两年。他莫昔芬曾是标准的初始治疗药物，与无病生存期的改善相关，但在降低局部区域复发方面可能比远处转移更有效。初始辅助来曲唑治疗在治疗过程早期也显示出远处转移风险的显著降低。如果不预先使用AIs，在他莫昔芬之后序贯使用依西美坦或阿那曲唑比继续使用他莫昔芬能提供更大的防复发保护。与AIs雌激素剥夺相关的副作用比他莫昔芬的副作用轻，且易于管理。各种分子标志物正在作为预测新辅助治疗反应的替代指标进行研究，这反过来可能预测对辅助治疗的反应性。治疗乳腺癌患者并开具内分泌治疗药物的外科医生应了解所有治疗策略，包括新辅助和辅助激素治疗，并告知患者其益处和潜在副作用。应与患者讨论AI治疗的早期和长期风险降低情况，以及常见的AI相关不良事件的管理。
