Breast Care Center, University of California at San Francisco, 1600 Divisadero St, 2nd Floor, Box 1710, San Francisco, CA 94115, USA.
J Clin Oncol. 2012 Sep 10;30(26):3242-9. doi: 10.1200/JCO.2011.39.2779. Epub 2012 May 29.
Neoadjuvant chemotherapy for breast cancer provides critical information about tumor response; how best to leverage this for predicting recurrence-free survival (RFS) is not established. The I-SPY 1 TRIAL (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis) was a multicenter breast cancer study integrating clinical, imaging, and genomic data to evaluate pathologic response, RFS, and their relationship and predictability based on tumor biomarkers.
Eligible patients had tumors ≥ 3 cm and received neoadjuvant chemotherapy. We determined associations between pathologic complete response (pCR; defined as the absence of invasive cancer in breast and nodes) and RFS, overall and within receptor subsets.
In 221 evaluable patients (median tumor size, 6.0 cm; median age, 49 years; 91% classified as poor risk on the basis of the 70-gene prognosis profile), 41% were hormone receptor (HR) negative, and 31% were human epidermal growth factor receptor 2 (HER2) positive. For 190 patients treated without neoadjuvant trastuzumab, pCR was highest for HR-negative/HER2-positive patients (45%) and lowest for HR-positive/HER2-negative patients (9%). Achieving pCR predicted favorable RFS. For 172 patients treated without trastuzumab, the hazard ratio for RFS of pCR versus no pCR was 0.29 (95% CI, 0.07 to 0.82). pCR was more predictive of RFS by multivariate analysis when subtype was taken into account, and point estimates of hazard ratios within the HR-positive/HER2-negative (hazard ratio, 0.00; 95% CI, 0.00 to 0.93), HR-negative/HER2-negative (hazard ratio, 0.25; 95% CI, 0.04 to 0.97), and HER2-positive (hazard ratio, 0.14; 95% CI, 0.01 to 1.0) subtypes are lower. Ki67 further improved the prediction of pCR within subsets.
In this biologically high-risk group, pCR differs by receptor subset. pCR is more highly predictive of RFS within every established receptor subset than overall, demonstrating that the extent of outcome advantage conferred by pCR is specific to tumor biology.
乳腺癌新辅助化疗可提供有关肿瘤反应的重要信息；但如何最好地利用这些信息来预测无复发生存率（RFS）尚不确定。I-SPY1 试验（通过影像学和分子分析预测治疗反应的研究）是一项多中心乳腺癌研究，整合了临床、影像学和基因组数据，以评估病理反应、RFS 及其关系，并基于肿瘤生物标志物进行预测。
符合条件的患者肿瘤≥3cm，并接受新辅助化疗。我们确定了病理完全缓解（pCR；定义为乳房和淋巴结中无浸润性癌）与 RFS 的关系，以及整体和受体亚组内的关系。
在 221 例可评估患者中（中位肿瘤大小 6.0cm；中位年龄 49 岁；91%根据 70 基因预后图谱被归类为高危），41%为激素受体（HR）阴性，31%为人表皮生长因子受体 2（HER2）阳性。对于 190 例未接受新辅助曲妥珠单抗治疗的患者，HR 阴性/HER2 阳性患者的 pCR 最高（45%），HR 阳性/HER2 阴性患者的 pCR 最低（9%）。pCR 预测了有利的 RFS。对于 172 例未接受曲妥珠单抗治疗的患者，pCR 与无 pCR 的 RFS 风险比为 0.29（95%CI，0.07 至 0.82）。当考虑到亚型时，pCR 通过多变量分析对 RFS 的预测更具预测性，并且 HR 阳性/HER2 阴性（风险比，0.00；95%CI，0.00 至 0.93）、HR 阴性/HER2 阴性（风险比，0.25；95%CI，0.04 至 0.97）和 HER2 阳性（风险比，0.14；95%CI，0.01 至 1.0）亚组的风险比估计值较低。Ki67 进一步提高了亚组内 pCR 的预测能力。
在这个生物学高危组中，pCR 因受体亚型而异。pCR 在每个既定受体亚组内对 RFS 的预测均优于整体，表明 pCR 带来的预后优势程度与肿瘤生物学有关。
