Brekelmans C T M, Tilanus-Linthorst M M A, Seynaeve C, vd Ouweland A, Menke-Pluymers M B E, Bartels C C M, Kriege M, van Geel A N, Burger C W, Eggermont A M M, Meijers-Heijboer H, Klijn J G M
Department of Medical Oncology, Family Cancer Clinic, Erasmus MC-Daniel den Hoed Cancer Center, P.O. Box 5201, 3008 AE Rotterdam, The Netherlands.
Eur J Cancer. 2007 Mar;43(5):867-76. doi: 10.1016/j.ejca.2006.12.009. Epub 2007 Feb 20.
Results on tumour characteristics and survival of hereditary breast cancer (BC), especially on BRCA2-associated BC, are inconclusive. The prognostic impact of the classical tumour and treatment factors in hereditary BC is insufficiently known.
We selected 103 BRCA2-, 223 BRCA1- and 311 non-BRCA1/2 BC patients (diagnosis 1980-2004) from the Rotterdam Family Cancer Clinic. To correct for longevity bias, analyses were also performed while excluding index patients undergoing DNA testing 2 years after BC diagnosis. As a comparison group, 759 sporadic BC patients of comparable age at and year of diagnosis were selected. We compared tumour characteristics, the occurrence of ipsilateral recurrence (LRR) and contralateral BC (CBC) as well as distant disease-free (DDFS), BC-specific (BCSS) and overall survival (OS) between these groups. By multivariate modelling, the prognostic impact of tumour and treatment factors was investigated separately in hereditary BC.
We confirmed the presence of the particular BRCA1-phenotype. In contrast, tumour characteristics of BRCA2-associated BC were similar to those of non-BRCA1/2 and sporadic BC, with the exception of a high risk of CBC (3.1% per year) and oestrogen-receptor (ER)-positivity (83%). No significant differences between BRCA2-associated BC and other BC subgroups were found with respect to LRR, DDFS, BCSS and OS. Independent prognostic factors for BC-specific survival in hereditary BC (combining the three subgroups) were tumour stage, adjuvant chemotherapy, histologic grade, ER status and a prophylactic (salpingo-)oophorectomy.
Apart from the frequent occurrence of contralateral BC and a positive ER-status, BRCA2-associated BC did not markedly differ from other hereditary or sporadic BC. Our observation that tumour size and nodal status are prognostic factors also in hereditary BC implies that the strategy to use these factors as a proxy for ultimate mortality appears to be valid also in this specific group of patients.
关于遗传性乳腺癌（BC）的肿瘤特征和生存结果，尤其是与BRCA2相关的乳腺癌，尚无定论。遗传性乳腺癌中经典肿瘤和治疗因素的预后影响尚不清楚。
我们从鹿特丹家庭癌症诊所选取了103例BRCA2、223例BRCA1和311例非BRCA1/2乳腺癌患者（诊断时间为1980 - 2004年）。为校正长寿偏倚，分析时还排除了乳腺癌诊断后2年接受DNA检测的索引患者。作为对照组，选取了759例诊断时年龄和年份相近的散发性乳腺癌患者。我们比较了这些组之间的肿瘤特征、同侧复发（LRR）和对侧乳腺癌（CBC）的发生率以及远处无病生存（DDFS）、乳腺癌特异性生存（BCSS）和总生存（OS）。通过多变量建模，分别研究了遗传性乳腺癌中肿瘤和治疗因素的预后影响。
我们证实了特定BRCA1表型的存在。相比之下，除了CBC高风险（每年3.1%）和雌激素受体（ER）阳性率高（83%）外，与BRCA2相关的乳腺癌的肿瘤特征与非BRCA1/2和散发性乳腺癌相似。在LRR、DDFS、BCSS和OS方面，与BRCA2相关的乳腺癌和其他乳腺癌亚组之间未发现显著差异。遗传性乳腺癌（合并三个亚组）中乳腺癌特异性生存的独立预后因素是肿瘤分期、辅助化疗、组织学分级、ER状态和预防性（输卵管 - ）卵巢切除术。
除了对侧乳腺癌的频繁发生和ER状态阳性外，与BRCA2相关的乳腺癌与其他遗传性或散发性乳腺癌没有明显差异。我们观察到肿瘤大小和淋巴结状态也是遗传性乳腺癌的预后因素，这意味着在这一特定患者群体中，将这些因素用作最终死亡率替代指标的策略似乎也是有效的。
