HER-2、p53、p21和激素受体蛋白表达作为新辅助多西他赛联合表柔比星治疗局部晚期乳腺癌反应和预后的预测因素。
HER-2, p53, p21 and hormonal receptors proteins expression as predictive factors of response and prognosis in locally advanced breast cancer treated with neoadjuvant docetaxel plus epirubicin combination.
作者信息
Tiezzi Daniel G, Andrade Jurandyr M, Ribeiro-Silva Alfredo, Zola Fábio E, Marana Heitor R C, Tiezzi Marcelo G
机构信息
Department of Gynecology and Obstetrics, Breast Disease Division, Ribeirao Preto School of Medicine, HCFMRP-USP, Ribeirão Preto, São Paulo, Brazil.
出版信息
BMC Cancer. 2007 Feb 26;7:36. doi: 10.1186/1471-2407-7-36.
BACKGROUND
Neoadjuvant chemotherapy has been considered the standard care in locally advanced breast cancer. However, about 20% of the patients do not benefit from this clinical treatment and, predictive factors of response were not defined yet. This study was designed to evaluate the importance of biological markers to predict response and prognosis in stage II and III breast cancer patients treated with taxane and anthracycline combination as neoadjuvant setting.
METHODS
Sixty patients received preoperative docetaxel (75 mg/m2) in combination with epirubicin (50 mg/m2) in i.v. infusion in D1 every 3 weeks after incisional biopsy. They received adjuvant chemotherapy with CMF or FEC, attaining axillary status following definitive breast surgery. Clinical and pathologic response rates were measured after preoperative therapy. We evaluated the response rate to neoadjuvant chemotherapy and the prognostic significance of clinicopathological and immunohistochemical parameters (ER, PR, p51, p21 and HER-2 protein expression). The median patient age was 50.5 years with a median follow up time 48 months after the time of diagnosis.
RESULTS
Preoperative treatment achieved clinical response in 76.6% of patients and complete pathologic response in 5%. The clinical, pathological and immunohistochemical parameters were not able to predict response to therapy and, only HER2 protein overexpression was associated with a decrease in disease free and overall survival (P = 0.0007 and P = 0.003) as shown by multivariate analysis.
CONCLUSION
Immunohistochemical phenotypes were not able to predict response to neoadjuvant chemotherapy. Clinical response is inversely correlated with a risk of death in patients submitted to neoadjuvant chemotherapy and HER2 overexpression is the major prognostic factor in stage II and III breast cancer patients treated with a neoadjuvant docetaxel and epirubicin combination.
背景
新辅助化疗一直被视为局部晚期乳腺癌的标准治疗方法。然而，约20%的患者无法从这种临床治疗中获益，且尚未明确反应的预测因素。本研究旨在评估生物标志物在预测接受紫杉烷和蒽环类药物联合新辅助治疗的II期和III期乳腺癌患者的反应及预后方面的重要性。
方法
60例患者在切开活检后，每3周于第1天静脉输注多西他赛（75mg/m²）联合表柔比星（50mg/m²）进行术前治疗。他们接受CMF或FEC辅助化疗，在确定性乳房手术后确定腋窝状态。术前治疗后测量临床和病理反应率。我们评估了新辅助化疗的反应率以及临床病理和免疫组化参数（ER、PR、p51、p21和HER-2蛋白表达）的预后意义。患者中位年龄为50.5岁，诊断后中位随访时间为48个月。
结果
术前治疗使76.6%的患者获得临床反应，5%的患者获得完全病理反应。临床、病理和免疫组化参数均无法预测治疗反应，多因素分析显示，只有HER2蛋白过表达与无病生存期和总生存期缩短相关（P = 0.0007和P = 0.003）。
结论
免疫组化表型无法预测新辅助化疗的反应。新辅助化疗患者的临床反应与死亡风险呈负相关，HER2过表达是接受新辅助多西他赛和表柔比星联合治疗的II期和III期乳腺癌患者的主要预后因素。
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