Ferretti Stefano, Sassoli de Bianchi Priscilla, Canuti Debora, Campari Cinzia, Cortesi Laura, Arcangeli Valentina, Barbieri Elena, D'Aloia Cecilia, Danesi Rita, De Iaco Pierandrea, De Lillo Margherita, Lombardo Laura, Moretti Gabriella, Musolino Antonino, Palli Dante, Palmonari Caterina, Ravegnani Mila, Tafà Alfredo, Tononi Alessandra, Turchetti Daniela, Zamagni Claudio, Zampiga Valentina, Bucchi Lauro
Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, 44121 Ferrara, Italy.
Local Health Authority, 44121 Ferrara, Italy.
Methods Protoc. 2024 Aug 13;7(4):63. doi: 10.3390/mps7040063.
Hereditary breast/ovarian cancer (HBOC) syndrome is caused by the inheritance of monoallelic germline BRCA1/2 gene mutations. If BRCA1/2 mutation carriers are identified before the disease develops, effective actions against HBOC can be taken, including intensive screening, risk-reducing mastectomy and salpingo-oophorectomy, and risk-reducing medications. The Italian National Prevention Plan mandates the creation of regional BRCA genetic testing programmes. So far, however, only informal data have been reported on their implementation. We have designed a study aimed at evaluating the results of a population-based programme for risk assessment and genetic counselling and testing for BRCA1/2-related HBOC that is underway in the Emilia-Romagna region (northern Italy). The programme-which is entirely free-includes basic screening with an estimate of the likelihood of carrying a BRCA1/2 mutation using a familial risk assessment tool, a closer examination of women with suspected risk increase, an assessment of the need for further genetic counselling and, if needed, genetic testing and risk-reducing interventions. In this paper, the design of the programme and the protocol of the study are presented. The study has an observational, historical cohort design. Eligible are the women found to be at an increased risk of HBOC (profile 3 women). The main objectives are (i) to determine the precision of the programme in measuring the level of risk of HBOC for profile 3 women; (ii) to determine the characteristics of profile 3 women and their association with the risk management strategy chosen; (iii) to compare the age at onset, histologic type, tumour stage, molecular subtype, and prognosis of breast/ovarian cancers observed in the cohort of profile 3 women with the features of sporadic cancers observed in the general female population; (iv) to determine the level and the determinants of adherence to recommendations; and (v) to determine the appropriateness and timing of risk-reducing surgery and medications. Investigating the quality and results of the programme is necessary because the best practices in risk assessment and genetic counselling and testing for BRCA1/2-related cancer and the challenges they encounter should be identified and shared. The study has the potential to provide sound empirical evidence for the factors affecting the effectiveness of this type of service.
遗传性乳腺癌/卵巢癌（HBOC）综合征是由单等位基因种系BRCA1/2基因突变的遗传引起的。如果在疾病发生前识别出BRCA1/2突变携带者，就可以针对HBOC采取有效的措施，包括强化筛查、降低风险的乳房切除术和输卵管卵巢切除术，以及降低风险的药物治疗。意大利国家预防计划要求建立区域性BRCA基因检测项目。然而，到目前为止，关于这些项目实施情况的报告仅为非正式数据。我们设计了一项研究，旨在评估意大利北部艾米利亚-罗马涅地区正在进行的一项基于人群的BRCA1/2相关HBOC风险评估、遗传咨询和检测项目的结果。该项目完全免费，包括使用家族风险评估工具进行基本筛查，以估计携带BRCA1/2突变的可能性，对疑似风险增加的女性进行更仔细的检查，评估进一步遗传咨询的必要性，以及在需要时进行基因检测和降低风险的干预措施。本文介绍了该项目的设计和研究方案。该研究采用观察性历史队列设计。符合条件的是被发现患HBOC风险增加的女性（3型女性）。主要目标包括：（i）确定该项目在测量3型女性HBOC风险水平方面的准确性；（ii）确定3型女性的特征及其与所选风险管理策略的关联；（iii）比较3型女性队列中观察到的乳腺癌/卵巢癌发病年龄、组织学类型、肿瘤分期、分子亚型和预后与一般女性人群中散发性癌症的特征；（iv）确定对建议的依从性水平及其决定因素；（v）确定降低风险手术和药物治疗的适当性和时机。调查该项目的质量和结果是必要的，因为应识别和分享BRCA1/2相关癌症风险评估及遗传咨询和检测的最佳实践及其面临的挑战。该研究有可能为影响这类服务有效性的因素提供可靠的实证证据。
