de Bock G H, Schutte M, Krol-Warmerdam E M M, Seynaeve C, Blom J, Brekelmans C T M, Meijers-Heijboer H, van Asperen C J, Cornelisse C J, Devilee P, Tollenaar R A E M, Klijn J G M
Department of Medical Decision Making, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands.
J Med Genet. 2004 Oct;41(10):731-5. doi: 10.1136/jmg.2004.019737.
The germline CHEK2*1100delC variant has been associated with breast cancer in multiple case families where involvement of BRCA1 and BRCA2 has been excluded.
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).
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.
We conclude that carrying the CHEK21100delC 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 CHEK21100delC variant.
种系CHEK2*1100delC变异与多个病例家族中的乳腺癌相关，这些家族已排除BRCA1和BRCA2的参与。
我们通过对1084例连续的原发性乳腺癌患者进行前瞻性队列研究，调查了这种种系变异携带者的肿瘤特征和预后。收集了34例种系CHEK2*1100delC突变患者和102例无此突变患者的数据，按年龄和首次原发性乳腺癌诊断日期（1年内）分层。
携带者发生类固醇受体阳性肿瘤（雌激素受体（ER）：91%；孕激素受体（PR）：81%）的频率高于非携带者（ER：69%；PR：53%；p = 0.04）。突变携带者有患乳腺癌的女性一级或二级亲属的频率更高（p = 0.03），或有患乳腺癌或卵巢癌的任何一级或二级亲属的频率更高（p = 0.04）。CHEK2变异患者在对侧乳腺癌发生、无远处转移生存和无病生存方面预后更差（相对风险（RR）= 5.74；95%置信区间（CI）1.67至19.65），（RR = 2.81；95% CI 1.20至6.58），以及无病生存（RR = 3.86；95% CI 1.91至7.78）。在中位随访3.8年时，尚未发现总体生存方面的差异。
我们得出结论，携带CHEK21100delC突变是乳腺癌的不良预后指标。如果得到其他人的独立证实，对于新诊断的携带CHEK21100delC变异的乳腺癌病例，应考虑强化监测以及可能的预防措施。
