Musolino Antonino, Michiara Maria, Bella Maria A, Naldi Nadia, Zanelli Paola, Bortesi Beatrice, Capelletti Marzia, Soldani Linda, Camisa Roberta, Martella Eugenia, Franciosi Vittorio, Savi Mario, Neri Tauro M, Ardizzoni Andrea, Cascinu Stefano
Medical Oncology Unit, University Hospital of Parma, Via Gramsci 14, 43100 Parma, Italy.
Tumori. 2005 Nov-Dec;91(6):505-12. doi: 10.1177/030089160509100611.
To evaluate the clinical features of breast cancer patients with genetic susceptibility to this disease and to investigate the contribution of BRCA1 germline mutations to the phenotype of these tumors.
We reviewed the clinical and pathological records of 102 women with suspected inherited susceptibility to breast cancer consecutively seen at the Genetic Oncology Service of Parma, Italy. Sixty-two patients with a high probability of harboring a germline, cancer-predisposing mutation were tested for BRCA1 mutations. Exon 11 was screened using the protein truncation test and detected mutations were confirmed by direct sequencing (DS). All other exons were analyzed by DS.
Among the 62 patients with a completed mutation analysis, 48 (77.4%) had wild-type BRCA1, six (9.6%) had variants of unclear significance, eight (13%) had deleterious mutations. BRCA1-associated breast cancers (BABC) were significantly less likely to be diagnosed at stage I than breast cancers in women without mutations (12.5% vs 51%; P = 0.045), more likely to have a high proliferation rate (100% vs 24%, P < 0.001), and more likely to be histological grade 3 (100% vs 14%, P < 0.001), estrogen and progesterone receptor negative (87.5% vs 13%, P < 0.001; 75% vs 23%, P = 0.004), and p53 positive (87.5% vs 30%, P = 0.023). All tumors with BRCA1 mutations were HER-2/neu negative compared with 57% of the non-BRCA1 tumors (P = 0.04). There were no significant differences between BABC and non-BABC in 20-year relapse-free survival, 20-year event-free survival, and 20-year overall survival.
In this population-based study, BABC seems to present with adverse molecular features when compared with non-BABC, although the prognosis appears to be similar.
评估具有乳腺癌遗传易感性的患者的临床特征，并研究BRCA1种系突变对这些肿瘤表型的影响。
我们回顾了意大利帕尔马遗传肿瘤科连续收治的102例疑似遗传性乳腺癌易感性女性患者的临床和病理记录。对62例携带种系癌症易感突变可能性较高的患者进行了BRCA1突变检测。使用蛋白质截短试验对第11外显子进行筛查，检测到的突变通过直接测序（DS）进行确认。所有其他外显子通过DS进行分析。
在62例完成突变分析的患者中，48例（77.4%）BRCA1为野生型，6例（9.6%）有意义不明确的变异，8例（13%）有有害突变。与无突变女性的乳腺癌相比，BRCA1相关乳腺癌（BABC）在I期诊断的可能性显著降低（12.5%对51%；P = 0.045），增殖率较高的可能性更大（100%对24%，P < 0.001），组织学3级的可能性更大（100%对14%，P < 0.001），雌激素和孕激素受体阴性的可能性更大（87.5%对13%，P < 0.001；75%对23%，P = 0.004），p53阳性的可能性更大（87.5%对30%，P = 0.023）。与57%的非BRCA1肿瘤相比，所有携带BRCA1突变的肿瘤均为HER-2/neu阴性（P = 0.04）。BABC与非BABC在20年无复发生存率、20年无事件生存率和20年总生存率方面无显著差异。
在这项基于人群的研究中，与非BABC相比，BABC似乎具有不良分子特征，尽管预后似乎相似。
