Anthracyclines have been a mainstay of breast cancer therapy for decades, with strong evidence demonstrating their impact on breast cancer survival. However, concerns regarding rare but serious long-term toxicities including cardiotoxicity and hematologic malignancies have driven interest in alternative adjuvant therapy options with more favorable toxicity profiles. This article provides an update of data that help inform clinicians of the role anthracyclines should play in adjuvant breast cancer therapy. Two recently reported large randomized trials-the Anthracycline in Early Breast Cancer and Western German Study Plan B studies-compared a taxane and cyclophosphamide regimen with an anthracycline, taxane, and cyclophosphamide regimen. Although the studies had conflicting results, together these studies suggest that the benefit of adjuvant anthracycline therapy over a nonanthracycline taxane-containing regimen is modest at best and may be primarily seen in patients with especially high-risk disease (i.e., triple-negative breast cancer, involvement of multiple lymph nodes). A third study-the MINDACT study-compared an anthracycline-based regimen to a nonanthracycline regimen, with similar outcomes in both groups. Despite the toxicities, no adjuvant breast cancer regimen has been shown to be superior to an anthracycline-taxane regimen in high-risk patients. These data can directly inform clinical decision-making in determining which patients warrant use of adjuvant anthracycline therapy. Future research may focus on confirming subgroups for whom it is reasonable to forgo adjuvant anthracyclines and validating predictive biomarkers or scores for anthracycline benefit.
Implications for practice: In patients with early breast cancer, the choice of adjuvant chemotherapy should be based on its effectiveness in reducing breast cancer recurrences and its short- and long-term toxicities. Although adjuvant anthracycline and taxane chemotherapy has the most data supporting its effectiveness, anthracyclines carry a small but important increased risk for cardiotoxicity and leukemia. Two recent clinical trials help describe the degree of benefit with adjuvant anthracycline therapy compared with taxane therapy alone. They suggest that in patients with hormone receptor-positive breast cancer and limited lymph node involvement, nonanthracycline taxane-based adjuvant therapy may be adequate.
摘要
背景。数十年来,蒽环类一直是乳腺癌治疗的主要药物,来自各方的有力证据表明,此类药物对乳腺癌患者的存活率产生了积极的影响。然而,此类药物罕有但却十分严重的长期毒性反应(包括心脏毒性与血液系统恶性肿瘤)令人担忧,因此,促使人们将注意力转向寻找具有更良好毒性特征的替代辅助治疗方案。本文提供了最新数据,可帮助临床医生了解蒽环类在乳腺癌辅助治疗中所发挥的作用。最近报告的两项大型随机试验(早期乳腺癌中使用蒽环类研究和西德研究集团B计划研究)将紫杉烷和环磷酰胺治疗方案与蒽环类、紫杉烷和环磷酰胺治疗方案进行了比较。尽管研究结果存在矛盾,但这些研究同时表明,相对于含有紫杉烷的非蒽环类治疗方案,蒽环类辅助治疗的疗效在最好的情况下也只是略有改善,且主要见于患有特别高危疾病(即三阴性乳腺癌,肿瘤累及多个淋巴结)的患者。第三项研究(MINDACT 研究)将基于蒽环类的治疗方案与非蒽环类治疗方案进行了对比,两组方案得出了相似的结果。尽管存在毒性,但研究表明,在治疗高危患者的过程中,没有一项乳腺癌辅助治疗方案的疗效优于蒽环类‐紫杉烷治疗方案。这些数据可直接指导临床决策,以确定哪些患者需要使用蒽环类辅助治疗。未来的研究可能会侧重于确定哪些患者亚群可合理放弃蒽环类辅助治疗,并针对蒽环类的疗效获益验证预测性生物标志物或评分。
实践意义
对于早期乳腺癌患者而言,应基于降低乳腺癌复发的有效性及短期和长期毒性来选择辅助化疗。尽管有大量数据支持蒽环类和紫杉烷辅助化疗的有效性,但蒽环类会增加心脏毒性和罹患白血病的风险(此类情况并不常见)。近期开展的两项临床试验可有助于了解,与仅采用紫杉烷的治疗方案相比,蒽环类辅助治疗是否产生了更显著的疗效。研究显示,激素受体阳性乳腺癌和淋巴结受累有限的患者,可能适合采用基于紫杉烷的非蒽环类辅助疗法。
Keywords: Adjuvant chemotherapy; Anthracycline; Breast cancer.
© AlphaMed Press 2018.