Tumour characteristics and prognosis of breast cancer patients carrying the germline CHEK2*1100delC variant
Tumour characteristics and prognosis of breast cancer patients carrying the germline CHEK2*1100delC variant
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DOI：
10.1136/jmg.2004.019737
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发表时间：
2004-10-01
影响因子：
4
通讯作者：
Klijn, JGM
中科院分区：
文献类型：
--
作者：
de Bock, GH;Schutte, M;Klijn, JGM
背景：胚系CHEK2*1100delC变异与乳腺癌有关，在BRCA1和BRCA2已被排除的多个病例家族中。方法：我们通过前瞻性队列研究的方法，在1084例连续的乳腺癌患者中调查了该胚系变异携带者的肿瘤特征和预后。收集了34例CHEK2*1100delC突变患者和102例无该突变的患者的资料，按年龄和首次诊断为乳腺癌的日期(1年内)分层。结果：携带者发生类固醇受体阳性肿瘤的频率(雌激素受体(ER)：91%；孕激素受体(PR)：81%)高于非携带者(ER：69%；PR：53%；P=0.04)。突变携带者多为女性乳腺癌的一级或二级亲属(p=0.03)，或乳腺癌或卵巢癌的一级或二级亲属(p=0.04)。CHEK2基因变异患者在对侧乳腺癌的发生(相对危险度RR=5.74；95%可信区间1.67~19.65)、无远处转移生存率(RR=2.81；95%可信区间1.20~6.58)和无瘤生存率(RR=3.86；95%可信区间1.91~7.78)方面预后较差。结论：携带CHEK2*1100delC突变是乳腺癌的不良预后指标。如果被其他人独立证实，对于携带CHEK2*1100delC变异的新诊断乳腺癌病例，应该考虑加强监测，并可能采取预防措施。
Background: The germline CHEK2*1100delC variant has been associated with breast cancer in multiple case families where involvement of BRCA1 and BRCA2 has been excluded.Methods: We have investigated the tumour characteristics and prognosis of carriers of this germline variant by means of a prospective cohort study in an unselected cohort of 1084 consecutive patients with primary breast cancer. Data were collected for 34 patients with a germline CHEK2*1100delC mutation and for 102 patients without this mutation, stratified by age and date of diagnosis of the first primary breast cancer (within 1 year).Results: Carriers developed steroid receptor positive tumours (oestrogen receptor (ER): 91%; progesterone receptor (PR): 81%) more frequently than non-carriers (ER: 69%; PR: 53%; p = 0.04). Mutation carriers more frequently had a female first or second degree relative with breast cancer (p = 0.03), or had any first or second degree relative with breast or ovarian cancer (p = 0.04). Patients with the CHEK2 variant had a more unfavourable prognosis regarding the occurrence of contralateral breast cancer (relative risk (RR) = 5.74; 95% confidence interval (CI) 1.67 to 19.65), distant metastasis-free survival (RR = 2.81; 95% CI 1.20 to 6.58), and disease-free survival (RR = 3.86; 95% CI 1.91 to 7.78). As yet, no difference with respect to overall survival has been found at a median follow up of 3.8 years.Conclusion: We conclude that carrying the CHEK2*1100delC mutation is an adverse prognostic indicator for breast cancer. If independently confirmed by others, intensive surveillance, and possibly preventive measures, should be considered for newly diagnosed breast cancer cases carrying the CHEK2*1100delC variant.