Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Clin Cancer Res. 2009 Dec 1;15(23):7381-8. doi: 10.1158/1078-0432.CCR-09-1735. Epub 2009 Nov 17.
To evaluate HER2 status in residual tumor identified at the time of surgery in patients not achieving a pathologic complete response (pCR) and to determine the effect of alterations in HER2 status on recurrence-free survival (RFS).
Clinicopathologic data for patients with HER2-overexpressing breast cancer receiving neoadjuvant therapy with a taxane, anthracycline, and concomitant trastuzumab between 2004 and 2007 were reviewed. Surgical specimens for patients achieving less than a pCR were assessed to determine if there was enough residual tissue to evaluate posttreatment HER2 status. RFS was determined using the Kaplan-Meier method and compared by the log-rank statistic.
A pCR was achieved in 72 of the 142 (50.7%) patients. Residual tumor was sufficient to assess posttreatment HER2 status in 25 patients. Fluorescence in situ hybridization done on pretreatment specimens confirmed HER2 amplification before beginning therapy. Eight (32.0%) posttreatment tumors were found to be HER2-negative by fluorescence in situ hybridization. At a median follow-up of 37 months (range, 8-56 months), the RFS was significantly better for patients with tumors that retained HER2 amplification (87.5% versus 50%, P = 0.04).
High pCR rates are achieved in patients with HER2-positive breast cancer treated with neoadjuvant trastuzumab in combination with anthracyclines and taxanes. One third of patients with significant residual disease loses HER2 amplification, and this change is associated with poor RFS. Residual tumor identified at the time of surgery should be reassessed for HER2 status, and novel adjuvant therapy strategies need to be studied in this population.
评估未达到病理完全缓解（pCR）的患者手术时残留肿瘤中 HER2 状态，并确定 HER2 状态改变对无复发生存率（RFS）的影响。
回顾了 2004 年至 2007 年间接受紫杉烷、蒽环类药物和曲妥珠单抗新辅助治疗的 HER2 过表达乳腺癌患者的临床病理数据。评估未达到 pCR 的患者的手术标本，以确定是否有足够的残留组织来评估治疗后 HER2 状态。使用 Kaplan-Meier 方法确定 RFS，并通过对数秩检验进行比较。
142 例患者中有 72 例（50.7%）达到 pCR。25 例患者的残留肿瘤足以评估治疗后 HER2 状态。在开始治疗前进行的荧光原位杂交证实了预处理标本中 HER2 的扩增。8 例（32.0%）治疗后的肿瘤通过荧光原位杂交被发现为 HER2 阴性。在中位随访 37 个月（范围，8-56 个月）时，肿瘤保留 HER2 扩增的患者 RFS 明显更好（87.5%对 50%，P=0.04）。
接受曲妥珠单抗联合蒽环类药物和紫杉烷新辅助治疗的 HER2 阳性乳腺癌患者可达到较高的 pCR 率。三分之一有大量残留疾病的患者失去了 HER2 扩增，这种变化与 RFS 不良相关。手术时残留的肿瘤应重新评估 HER2 状态，需要在这一人群中研究新的辅助治疗策略。
