Moller Pal, Evans D Gareth, Reis Marta M, Gregory Helen, Anderson Elaine, Maehle Lovise, Lalloo Fiona, Howell Anthony, Apold Jaran, Clark Neal, Lucassen Anneke, Steel C Michael
Section for Inherited Cancer, Department of Medical Genetics, Rikshospitalet-Radiumhospitalet Clinical Center, Oslo, Norway.
Int J Cancer. 2007 Sep 1;121(5):1017-20. doi: 10.1002/ijc.22789.
Women with a family history of breast cancer are commonly offered regular clinical or mammographic surveillance from age 30. Data on the efficacy of such programmes are limited. Clinical, pathological and outcome data were recorded on all breast and ovarian cancers diagnosed within familial breast cancer surveillance programmes at collaborating centers in Norway and the UK up to the end of 2005. These have been analyzed according to the mutation status of the affected women (BRCA1+ve, BRCA2+ve or mutation-negative). Breast cancer was diagnosed in 442 patients subsequently followed for a total of 2095 years. Eighty-nine (20%) had BRCA1 mutations, 35 (8%) BRCA2 mutations and in 318 (72%) no mutation could be detected ("mut neg"). Five-year survival in BRCA1 was 73% compared to 96% in BRCA2 and 92% in mut neg (p = 0.000). Among BRCA1 mutation-carriers, 5-year survival was 67% for cases diagnosed as carcinoma in situ, 84% for node-negative invasive cancers and 58% for those with nodal involvement (p > 0.05). For BRCA2 mutation-carriers the corresponding figures were 100, 100 and 90% (p > 0.05), while for mut neg women they were 100, 97 and 71% (p = 0.03). Regular surveillance in women at increased familial risk of breast cancer is associated with a good outcome if they carry BRCA2 mutations or no detectable mutation. Carriers of BRCA1 mutations fare significantly worse, even when their tumors are diagnosed at an apparently early stage. The differences in outcome associated with different genetic causes of disease were associated with demonstrated differences in tumor biology. The findings demonstrate the outcome for genetically different breast cancers detected within a programme for early diagnosis and treatment, which is relevant to genetic counseling when women at risk have to chose between the options for preventing death from inherited breast cancer.
有乳腺癌家族史的女性通常从30岁起就会接受定期的临床或乳房X光检查监测。关于此类项目效果的数据有限。截至2005年底，挪威和英国合作中心的家族性乳腺癌监测项目中诊断出的所有乳腺癌和卵巢癌的临床、病理及转归数据均有记录。这些数据已根据受影响女性的突变状态（BRCA1阳性、BRCA2阳性或突变阴性）进行了分析。442例患者被诊断出患有乳腺癌，随后共随访了2095年。89例（20%）有BRCA1突变，35例（8%）有BRCA2突变，318例（72%）未检测到突变（“突变阴性”）。BRCA1患者的5年生存率为73%，BRCA2患者为96%，突变阴性患者为92%（p = 0.000）。在BRCA1突变携带者中，原位癌诊断病例的5年生存率为67%，无淋巴结转移的浸润性癌为84%，有淋巴结受累的为58%（p > 0.05）。BRCA2突变携带者的相应数字分别为100%、100%和90%（p > 0.05），而突变阴性女性分别为100%、97%和71%（p = 0.03）。对于乳腺癌家族风险增加的女性，若携带BRCA2突变或未检测到突变，定期监测的转归良好。BRCA1突变携带者的情况则明显更差，即使其肿瘤在明显早期被诊断出来。与不同遗传病因相关的转归差异与已证实的肿瘤生物学差异有关。这些发现表明了在早期诊断和治疗项目中检测到的基因不同的乳腺癌的转归情况，这对于有风险的女性在预防遗传性乳腺癌死亡的选项之间进行选择时的遗传咨询具有重要意义。
