Mina Lida, Soule Sharon E, Badve Sunil, Baehner Fredrick L, Baker Joffre, Cronin Maureen, Watson Drew, Liu Mei-Lan, Sledge George W, Shak Steve, Miller Kathy D
Department of Medicine, Indiana University, RT-473, Indianapolis, IN, 46202, USA.
Breast Cancer Res Treat. 2007 Jun;103(2):197-208. doi: 10.1007/s10549-006-9366-x. Epub 2006 Oct 13.
Primary chemotherapy provides an ideal opportunity to correlate gene expression with response to treatment. We used paraffin-embedded core biopsies from a completed phase II trial to identify genes that correlate with response to primary chemotherapy.
Patients with newly diagnosed stage II or III breast cancer were treated with sequential doxorubicin 75 mg/M2 q2 wks x 3 and docetaxel 40 mg/M2 weekly x 6; treatment order was randomly assigned. Pretreatment core biopsy samples were interrogated for genes that might correlate with pathologic complete response (pCR). In addition to the individual genes, the correlation of the Oncotype DX Recurrence Score with pCR was examined.
Of 70 patients enrolled in the parent trial, core biopsies samples with sufficient RNA for gene analyses were available from 45 patients; 9 (20%) had inflammatory breast cancer (IBC). Six (14%) patients achieved a pCR. Twenty-two of the 274 candidate genes assessed correlated with pCR (p < 0.05). Genes correlating with pCR could be grouped into three large clusters: angiogenesis-related genes, proliferation related genes, and invasion-related genes. Expression of estrogen receptor (ER)-related genes and Recurrence Score did not correlate with pCR. In an exploratory analysis we compared gene expression in IBC to non-inflammatory breast cancer; twenty-four (9%) of the genes were differentially expressed (p < 0.05), 5 were upregulated and 19 were downregulated in IBC.
Gene expression analysis on core biopsy samples is feasible and identifies candidate genes that correlate with pCR to primary chemotherapy. Gene expression in IBC differs significantly from noninflammatory breast cancer.
原发性化疗为将基因表达与治疗反应相关联提供了理想机会。我们使用来自一项已完成的II期试验的石蜡包埋芯针活检样本，以鉴定与原发性化疗反应相关的基因。
新诊断的II期或III期乳腺癌患者接受序贯化疗，多柔比星75mg/M²，每2周一次，共3次，多西他赛40mg/M²，每周一次，共6次；治疗顺序随机分配。对预处理的芯针活检样本检测可能与病理完全缓解（pCR）相关的基因。除了单个基因外，还检测了Oncotype DX复发评分与pCR的相关性。
在参与母试验的70例患者中，45例患者有足够RNA用于基因分析的芯针活检样本；9例（20%）患有炎性乳腺癌（IBC）。6例（14%）患者达到pCR。在评估的274个候选基因中，22个与pCR相关（p<0.05）。与pCR相关的基因可分为三大类：血管生成相关基因、增殖相关基因和侵袭相关基因。雌激素受体（ER）相关基因的表达和复发评分与pCR无关。在一项探索性分析中，我们比较了IBC与非炎性乳腺癌的基因表达；24个（9%）基因表达存在差异（p<0.05），IBC中有5个上调，19个下调。
对芯针活检样本进行基因表达分析是可行的，并可鉴定出与原发性化疗pCR相关的候选基因。IBC中的基因表达与非炎性乳腺癌有显著差异。
