Kyndi Marianne, Sørensen Flemming B, Knudsen Helle, Alsner Jan, Overgaard Marie, Nielsen Hanne M, Overgaard Jens
Department of Experimental Clinical Oncology, Arhus University Hospital, Nørrebrogade, 8000 Arhus C, Denmark.
Breast Cancer Res. 2008;10(2):R24. doi: 10.1186/bcr1981. Epub 2008 Mar 20.
A significant survival improvement after postmastectomy radiotherapy was identified in the Danish Breast Cancer Cooperative Group (DBCG82) b and c studies and in the British Columbia Randomized Radiation Trial. Recently, potential predictive value regarding response to postmastectomy radiotherapy was reported for carbonic anhydrase (CA) IX in a study (reported in abstract form) that included 160 patients. The purpose of the present study was to examine the importance of CA IX to response to postmastectomy radiotherapy in the larger scaled DBCG82 b and c studies.
The DBCG82 b and c studies included 3,083 high-risk Danish breast cancer patients. The women were randomly assigned to postmastectomy radiotherapy plus systemic therapy (cyclophosfamide, methotrexate and fluorouracil in premenopausal women; and tamoxifen in postmenopausal women) or to systemic therapy alone. Cores from invasive tumour-containing paraffin blocks from 1,000 patients (more than seven nodes surgically removed) were transferred to tissue microarrays. Tissue microarray sections were stained immunohistochemically for CA IX (M75). The median follow up for patients remaining alive was 17 years. Clinical end-points were loco-regional recurrence, distant metastases, disease-specific survival and overall survival. Statistical analyses included kappa statistics, chi2 or exact tests, Kaplan-Meier probability plots, Log-rank test and Cox regression analyses.
CA IX was assessable in 945 cores. The percentage of tumours positive for CA IX was 16% (> or = 10% invasive tumour staining). CA IX was not an independent prognostic marker for survival, distant metastases, or locoregional recurrence in the subgroup of 945 patients or within either of the two randomization arms. In subgroup analyses, however, CA IX was an independent prognostic marker for overall survival among postmenopausal women (P = 0.001), women with one to three positive nodes (P = 0.02) and hormone receptor positive women (P = 0.001). Fifteen-year probabilities of overall survival were improved by 9% and 7% after postmastectomy radiotherapy for the subgroups of CA IX negative and CA IX positive patients, respectively.
Within this series of 945 high-risk premenopausal and postmenopausal women, positivity for CA IX was not overall an independent prognostic marker for survival; only in subgroup analyses was it found to have prognostic value. The improvement in 15-year survival after postmastectomy radiotherapy was of similar magnitude in the two subgroups of CA IX positive and CA IX negative patients.
在丹麦乳腺癌协作组（DBCG82）b和c研究以及不列颠哥伦比亚随机放疗试验中，已证实乳房切除术后放疗可显著提高生存率。最近，一项纳入160例患者的研究（以摘要形式报道）显示，碳酸酐酶（CA）IX对乳房切除术后放疗的反应具有潜在预测价值。本研究的目的是在规模更大的DBCG82 b和c研究中，探讨CA IX对乳房切除术后放疗反应的重要性。
DBCG82 b和c研究纳入了3083例高危丹麦乳腺癌患者。这些女性被随机分配至乳房切除术后放疗联合全身治疗（绝经前女性使用环磷酰胺、甲氨蝶呤和氟尿嘧啶；绝经后女性使用他莫昔芬）或单纯全身治疗组。从1000例患者（手术切除超过7个淋巴结）的含浸润性肿瘤石蜡块中获取组织芯，并转移至组织微阵列。组织微阵列切片进行CA IX（M75）免疫组织化学染色。对存活患者的中位随访时间为17年。临床终点为局部区域复发、远处转移、疾病特异性生存和总生存。统计分析包括kappa统计、卡方检验或确切概率检验、Kaplan-Meier生存曲线、Log-rank检验和Cox回归分析。
945个组织芯可进行CA IX评估。CA IX阳性肿瘤的比例为16%（浸润性肿瘤染色≥10%）。在945例患者亚组或两个随机分组组中的任何一组中，CA IX均不是生存、远处转移或局部区域复发的独立预后标志物。然而，在亚组分析中，CA IX是绝经后女性（P = 0.001）、有1至3个阳性淋巴结的女性（P = 0.02）和激素受体阳性女性（P = 0.001）总生存的独立预后标志物。CA IX阴性和CA IX阳性患者亚组在乳房切除术后放疗后的15年总生存概率分别提高了9%和7%。
在这945例高危绝经前和绝经后女性中，CA IX阳性总体上不是生存的独立预后标志物；仅在亚组分析中发现其具有预后价值。CA IX阳性和CA IX阴性患者亚组在乳房切除术后放疗后的15年生存率提高幅度相似。
