Cheang Maggie C U, Voduc David, Bajdik Chris, Leung Samuel, McKinney Steven, Chia Stephen K, Perou Charles M, Nielsen Torsten O
Genetic Pathology Evaluation Centre, Vancouver Coastal Health Research Institute, British Columbia Cancer Agency, and University of British Columbia, Vancouver, British Columbia, Canada.
Clin Cancer Res. 2008 Mar 1;14(5):1368-76. doi: 10.1158/1078-0432.CCR-07-1658.
Basal-like breast cancer is associated with high grade, poor prognosis, and younger patient age. Clinically, a triple-negative phenotype definition [estrogen receptor, progesterone receptor, and human epidermal growth factor receptor (HER)-2, all negative] is commonly used to identify such cases. EGFR and cytokeratin 5/6 are readily available positive markers of basal-like breast cancer applicable to standard pathology specimens. This study directly compares the prognostic significance between three- and five-biomarker surrogate panels to define intrinsic breast cancer subtypes, using a large clinically annotated series of breast tumors.
Four thousand forty-six invasive breast cancers were assembled into tissue microarrays. All had staging, pathology, treatment, and outcome information; median follow-up was 12.5 years. Cox regression analyses and likelihood ratio tests compared the prognostic significance for breast cancer death-specific survival (BCSS) of the two immunohistochemical panels.
Among 3,744 interpretable cases, 17% were basal using the triple-negative definition (10-year BCSS, 6 7%) and 9% were basal using the five-marker method (10-year BCSS, 62%). Likelihood ratio tests of multivariable Cox models including standard clinical variables show that the five-marker panel is significantly more prognostic than the three-marker panel. The poor prognosis of triple-negative phenotype is conferred almost entirely by those tumors positive for basal markers. Among triple-negative patients treated with adjuvant anthracycline-based chemotherapy, the additional positive basal markers identified a cohort of patients with significantly worse outcome.
The expanded surrogate immunopanel of estrogen receptor, progesterone receptor, human HER-2, EGFR, and cytokeratin 5/6 provides a more specific definition of basal-like breast cancer that better predicts breast cancer survival.
基底样乳腺癌与高分级、预后不良及患者年龄较轻相关。临床上，通常采用三阴性表型定义（雌激素受体、孕激素受体和人表皮生长因子受体（HER）-2均为阴性）来识别此类病例。表皮生长因子受体（EGFR）和细胞角蛋白5/6是适用于标准病理标本的基底样乳腺癌现成的阳性标志物。本研究使用大量具有临床注释的乳腺肿瘤系列，直接比较用于定义内在性乳腺癌亚型的三标志物和五标志物替代检测板之间的预后意义。
将4046例浸润性乳腺癌制成组织微阵列。所有病例均有分期、病理、治疗及转归信息；中位随访时间为12.5年。采用Cox回归分析和似然比检验比较两种免疫组化检测板对乳腺癌特异性生存（BCSS）的预后意义。
在3744例可解释病例中，采用三阴性定义时17%为基底样（10年BCSS为67%），采用五标志物方法时9%为基底样（10年BCSS为62%）。包含标准临床变量的多变量Cox模型的似然比检验显示，五标志物检测板的预后意义显著高于三标志物检测板。三阴性表型的不良预后几乎完全由那些基底标志物阳性的肿瘤所致。在接受基于蒽环类辅助化疗的三阴性患者中，额外的基底标志物阳性确定了一组预后明显较差的患者。
雌激素受体、孕激素受体、人HER-2、EGFR和细胞角蛋白5/6的扩展替代免疫检测板为基底样乳腺癌提供了更具体的定义，能更好地预测乳腺癌生存情况。
