Nolen Brian M, Marks Jeffrey R, Ta'san Shlomo, Rand Alex, Luong The Minh, Wang Yun, Blackwell Kimberly, Lokshin Anna E
University of Pittsburgh Cancer Institute, Hillman Cancer Center, Suite 1,19d, 5117 Centre Avenue, Pittsburgh, PA 15213, USA.
Breast Cancer Res. 2008;10(3):R45. doi: 10.1186/bcr2096. Epub 2008 May 12.
Neoadjuvant chemotherapy has become the standard of care for the diverse population of women diagnosed with locally advanced breast cancer. Serum biomarker levels are increasingly being investigated for their ability to predict therapy response and aid in the development of individualized treatment regimens. Multianalyte profiles may offer greater predictive power for neoadjuvant treatment response than the individual biomarkers currently in use.
Serum samples were collected from 44 patients enrolled in a phase I-II, open-label study of liposomal doxorubicin and paclitaxel in combination with whole breast hyperthermia for the neoadjuvant treatment of locally advanced breast cancer (stage IIB or stage III). Samples were collected prior to each of four rounds of treatment and prior to definitive surgery. Samples were assayed by Luminex assay for 55 serum biomarkers, including cancer antigens, growth/angiogenic factors, apoptosis-related molecules, metastasis-related molecules, adhesion molecules, adipokines, cytokines, chemokines, hormones, and other proteins.
Biomarker levels were compared retrospectively with clinical and pathologic treatment responses. Univariate analysis of the data identified several groups of biomarkers that differed significantly among treatment outcome groups early in the course of neoadjuvant chemotherapy. Multivariate statistical analysis revealed multibiomarker panels that could differentiate between treatment response groups with high sensitivity and specificity.
We demonstrate here that serum biomarker profiles may offer predictive power concerning treatment response and outcome in the neoadjuvant setting. The continued development of these findings will be of considerable clinical utility in the design of treatment regimens for individual breast cancer patients.
#NCT00346229.
新辅助化疗已成为诊断为局部晚期乳腺癌的不同女性群体的标准治疗方法。血清生物标志物水平因其预测治疗反应和辅助制定个体化治疗方案的能力而受到越来越多的研究。与目前使用的单个生物标志物相比，多分析物谱可能对新辅助治疗反应具有更大的预测能力。
从44名患者中收集血清样本，这些患者参加了一项I-II期开放标签研究，该研究使用脂质体阿霉素和紫杉醇联合全乳热疗对局部晚期乳腺癌（IIB期或III期）进行新辅助治疗。在四轮治疗的每一轮之前以及确定性手术之前采集样本。通过Luminex分析对55种血清生物标志物进行检测，包括癌症抗原、生长/血管生成因子、凋亡相关分子、转移相关分子、粘附分子、脂肪因子、细胞因子、趋化因子、激素和其他蛋白质。
将生物标志物水平与临床和病理治疗反应进行回顾性比较。对数据的单变量分析确定了几组生物标志物，这些生物标志物在新辅助化疗过程早期的治疗结果组之间存在显著差异。多变量统计分析揭示了能够以高灵敏度和特异性区分治疗反应组的多生物标志物面板。
我们在此证明，血清生物标志物谱可能提供关于新辅助治疗环境中治疗反应和结果的预测能力。这些发现的持续发展在为个体乳腺癌患者设计治疗方案方面将具有相当大的临床实用性。
#NCT00346229。
