School of Medicine, UHW Main Building, Cardiff, UK.
All Wales Medical Genetics Service, Institute of Medical Genetics, University Hospital of Wales, Cardiff, UK.
J Obstet Gynaecol. 2021 Aug;41(6):962-965. doi: 10.1080/01443615.2020.1820466. Epub 2020 Nov 23.
The objective of this study was to compare the pick-up rate of pathogenic variants in those with a high-grade serous ovarian carcinoma (HGSOC) undergoing oncology-led testing with the traditional genetics family history-based testing model. With novel therapies, status can affect treatment. Welsh oncologists are now testing all women with HGSOC at diagnosis rather than referring to genetics, where family history is required for testing. The records of 332 women who underwent testing via oncology were analysed. The outcome measures were; percentage of women with a pathogenic variant and the difference in identification of pathogenic variants between the oncology-led and traditional genetics testing models. Of the 332 women, 25 women (7.5%) tested positive for a pathogenic variant. This was slightly lower than the detection rate of 9.8% for patients tested via the genetics service over the same period. Testing through genetics, using family history criteria would have identified only 19 (76%) of those with pathogenic variants in the oncology cohort. Since women with a pathogenic variant can be offered life-extending targeted treatment and a significant proportion of these women would be missed if testing was offered based on family history criteria alone, universal testing of all women with HGSOC is justified.Impact statement: It is well established that individuals with a strong family history of breast and ovarian cancer are more likely to carry a pathogenic gene variant. With the use of tools such as the Manchester scoring system women are often invited for testing through clinical genetics services. Until recently there was no clinical impact for those already diagnosed with ovarian cancer. Our study has shown that the diagnosis of high grade serious ovarian carcinoma alone without the need for any family history leads to a similar rate of detection of pathogenic variants as traditional methods. With the advent of targeted treatments such as olaparib, women with a pathogenic variant can access different life extending treatment options. With comparable pick-up rates to traditional family history based scoring systems, oncologists can now arrange gene testing directly. Our study shows universal genetic testing of those with high-grade serious ovarian carcinoma by oncologists allows more women to access life extending treatment in a shorter timeframe compared to the traditional testing model used by clinical genetics services. We hope that other centres, both in the UK and beyond, will adopt this approach.
本研究的目的是比较接受肿瘤学主导检测的高分级浆液性卵巢癌（HGSOC）患者与传统基于遗传家族史的检测模式之间致病性变体的检出率。随着新型疗法的出现，状态可能会影响治疗。威尔士肿瘤学家现在在诊断时对所有 HGSOC 女性进行检测，而不是参考遗传咨询，遗传咨询需要家族史才能进行检测。分析了 332 名通过肿瘤学检测的女性的记录。主要观察指标为：致病性变体女性的百分比以及肿瘤学主导与传统遗传检测模型之间致病性变体识别的差异。在 332 名女性中，25 名（7.5%）检测出致病性变体呈阳性。这略低于同期通过遗传服务检测的患者 9.8%的检出率。通过遗传学检测，使用家族史标准，仅能在肿瘤学队列中识别出 19 名（76%）具有致病性变体的患者。由于携带致病性变体的女性可以接受延长生命的靶向治疗，如果仅基于家族史标准提供检测，那么相当一部分女性将被遗漏，因此对所有 HGSOC 女性进行普遍检测是合理的。
众所周知，具有强烈乳腺癌和卵巢癌家族史的个体更有可能携带致病性基因变体。利用曼彻斯特评分系统等工具，女性通常会通过临床遗传学服务接受检测。直到最近，对于已经诊断出患有卵巢癌的女性来说，这并没有临床影响。我们的研究表明，仅诊断为高级别浆液性卵巢癌，无需任何家族史，就可以达到与传统方法相似的致病性变体检出率。随着奥拉帕利等靶向治疗的出现，携带致病性变体的女性可以获得不同的延长生命的治疗选择。与传统基于家族史评分系统的检出率相当，肿瘤学家现在可以直接安排基因检测。我们的研究表明，肿瘤学家对高级别浆液性卵巢癌患者进行普遍遗传检测，可以使更多女性在更短的时间内获得延长生命的治疗，与临床遗传学服务使用的传统检测模式相比。我们希望英国和其他国家的其他中心也能采用这种方法。
