The Breast Cancer Susceptibility Mutation PALB2 1592delT Is Associated with an Aggressive Tumor Phenotype
The Breast Cancer Susceptibility Mutation PALB2 1592delT Is Associated with an Aggressive Tumor Phenotype
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DOI：
10.1158/1078-0432.ccr-08-3128
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发表时间：
2009-05-01
影响因子：
11.5
通讯作者：
Nevanlinna, Heli
中科院分区：
文献类型：
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作者：
Heikkinen, Tuomas;Karkkainen, Hanni;Nevanlinna, Heli
目的：确定乳腺癌易感性突变PALB 2 1592 delT对肿瘤表型和患者存活率的影响。我们确定了947例家族性和1,274例散发性乳腺癌患者以及1,079例人群对照的PALB 2突变状态，并将突变携带者的肿瘤特征和生存率与其他家族性和散发性病例以及79例BRCA 1和104例BRCA 2突变携带者进行了比较cases.Results:PALB 2 1592 delT突变在19例家族性[2.0%;比值比，11.03; 95%可信区间（95%CI），2.65-97.78; P < 0.0001]和8例散发患者中发现（0.6%;比值比，3.40; 95% CI，0.68-32.95; P = 0.1207）与两个（0.2%）对照个体进行比较。PALB 2突变携带者的肿瘤呈现三阴性（雌激素受体阴性/孕激素受体阴性/HER阴性）表型的频率（54.5%; P < 0.0001）高于其他家族性（12.2%）或散发性（9.4%）乳腺癌患者。它们也更常见于较高级别（分别为P 0.0027和P = 0.0017），并且具有较高的Ki 67表达（分别为P = 0.0004和P 0.0490）。携带PALB 2突变也与生存率降低相关，尤其是在家族性病例中（风险比，2.30; 95% CI，1.01-5.24; P = 0.0466）和家族性HER 2阴性肿瘤患者中（风险比，4.57; 95% CI，1.96-10.64; P = 0.0004）。携带BRCA 2突变也被发现是10年随访时生存率差的独立预测因子（P = 0.04）。结论：PALB 2 1592 delT突变对家族性乳腺癌风险有很强的影响。携带这种突变的患者中出现的肿瘤表现出与侵袭性疾病相关的表型。我们的研究结果还表明，携带BRCA 2突变对乳腺癌的长期生存有显著影响。
Purpose: To determine the effect of the breast cancer susceptibility mutation PALB2 1592delT on tumor phenotype and patient survival.Experimental Design: We defined the PALB2 mutation status in 947 familial and 1,274 sporadic breast cancer patients and 1,079 population controls, and compared tumor characteristics and survival in mutation carriers relative to other familial and sporadic cases and to 79 BRCA1 and 104 BRCA2 mutation carrier cases.Results: The PALB2 1592delT mutation was found in 19 familial [2.0%; odds ratio, 11.03; 95% confidence interval (95% Cl), 2.65-97.78; P < 0.0001] and eight sporadic patients (0.6%; odds ratio, 3.40; 95% Cl, 0.68-32.95; P = 0.1207) compared with two (0.2%) control individuals. Tumors of the PALB2 mutation carriers presented triple negative (estrogen receptor negative/progesterone receptor negative/HER negative) phenotype more often (54.5%; P < 0.0001) than those of other familial (12.2%) or sporadic (9.4%) breast cancer patients. They were also more often of higher grade (P 0.0027 and P = 0.0017, respectively) and had higher expression of Ki67 (P = 0.0004 and P 0.0490, respectively). Carrying a PALB2 mutation was also associated with reduced survival, especially in familial cases (hazard ratio, 2.30; 95% Cl, 1.01-5.24; P = 0.0466) and among familial patients with HER2-negative tumors (hazard ratio, 4.57; 95% Cl, 1.96-10.64; P = 0.0004). Carrying a BRCA2 mutation was also found to be an independent predictor of poor survival at 10-year follow-up (P = 0.04).Conclusions: The PALB2 1592delT mutation has a strong effect on familial breast cancer risk. The tumors rising in patients carrying this mutation manifest a phenotype associated with aggressive disease. Our results also suggest a significant impact of carrying a BRCA2 mutation on long-term breast cancer survival.