Edinburgh Cancer Centre, Edinburgh, UK.
Beatson West of Scotland Cancer Centre, Glasgow, UK.
BJOG. 2018 Oct;125(11):1451-1458. doi: 10.1111/1471-0528.15171. Epub 2018 May 10.
To determine the rates of germline BRCA1 and BRCA2 mutations in Scottish patients with ovarian cancer, before and after a change in testing policy.
Retrospective cohort study.
Four cancer/genetics centres in Scotland.
Patients with ovarian cancer undergoing germline BRCA1 and BRCA2 (gBRCA1/2) sequencing before 2013 (under the 'old criteria', with selection based solely on family history), after 2013 (under the 'new criteria', with sequencing offered to newly presenting patients with non-mucinous ovarian cancer), and in the 'prevalent population' (who presented before 2013, but were not eligible for sequencing under the old criteria but were sequenced under the new criteria).
Clinicopathological and sequence data were collected before and for 18 months after this change in selection criteria.
Frequency of germline BRCA1, BRCA2, RAD51C, and RAD51D mutations.
Of 599 patients sequenced, 205, 236, and 158 were in the 'old criteria', 'new criteria', and 'prevalent' populations, respectively. The frequency of gBRCA1/2 mutations was 30.7, 13.1, and 12.7%, respectively. The annual rate of gBRCA1/2 mutation detection was 4.2 before and 20.7 after the policy change. A total of 48% (15/31) 'new criteria' patients with gBRCA1/2 mutations had a Manchester score of <15 and would not have been offered sequencing based on family history criteria. In addition, 20 patients with gBRCA1/2 were identified in the prevalent population. The prevalence of gBRCA1/2 mutations in patients aged >70 years was 8.2%.
Sequencing all patients with non-mucinous ovarian cancer gives a much higher annual gBRCA1/2 mutation detection rate, with the frequency of positive tests still exceeding the 10% threshold upon which many family history-based models operate.
BRCA sequencing all non-mucinous cancer patients increases mutation detection five fold.
在苏格兰卵巢癌患者的种系 BRCA1 和 BRCA2 检测政策改变前后，确定种系 BRCA1 和 BRCA2（gBRCA1/2）突变的发生率。
回顾性队列研究。
苏格兰的 4 个癌症/遗传学中心。
在 2013 年之前接受种系 BRCA1 和 BRCA2（gBRCA1/2）测序的卵巢癌患者（根据“旧标准”，仅根据家族史进行选择），在 2013 年之后（根据“新标准”，对新出现的非粘液性卵巢癌患者进行测序），以及在“流行人群”（2013 年之前就诊，但不符合旧标准测序条件，但符合新标准测序条件）。
在选择标准改变前后 18 个月收集临床病理和序列数据。
种系 BRCA1、BRCA2、RAD51C 和 RAD51D 突变的频率。
在 599 例测序患者中，分别有 205、236 和 158 例患者属于“旧标准”、“新标准”和“流行”人群。gBRCA1/2 突变的频率分别为 30.7%、13.1%和 12.7%。在政策改变前后，gBRCA1/2 突变的年检测率分别为 4.2%和 20.7%。在有 gBRCA1/2 突变的“新标准”患者中，共有 48%（15/31）的患者曼彻斯特评分<15，根据家族史标准不会被建议进行测序。此外，在流行人群中还发现了 20 例 gBRCA1/2 患者。70 岁以上患者 gBRCA1/2 突变的患病率为 8.2%。
对所有非粘液性卵巢癌患者进行测序可大大提高每年 gBRCA1/2 突变的检测率，阳性检测的频率仍超过许多基于家族史模型的 10%阈值。
对所有非粘液性癌症患者进行 BRCA 测序可使突变检测率提高五倍。
