Lancet Oncol. 2010 Dec;11(12):1127-34. doi: 10.1016/S1470-2045(10)70263-1. Epub 2010 Nov 17.
Evidence supports a reduction in mortality from breast cancer with mammographic screening in the general population of women aged 40-49 years, but the effect of family history is not clear. We aimed to establish whether screening affects the disease stage and projected mortality of women younger than 50 years who have a clinically significant family history of breast cancer.
In the single-arm FH01 study, women at intermediate familial risk who were younger than 50 years were enrolled from 76 centres in the UK, and received yearly mammography. Women with BRCA mutations were not explicitly excluded, but would be rare in this group. To compare the FH01 cohort with women not receiving screening, two external comparison groups were used: the control group of the UK Age Trial (106,971 women aged 40-42 years at recruitment, from the general population [ie, average risk], followed up for 10 years), and a Dutch study of women with a family history of breast cancer (cancer cases aged 25-77 years, diagnosed 1980-2004). Study endpoints were size, node status, and histological grade of invasive tumours, and estimated mortality calculated from the Nottingham prognostic index (NPI) score, and adjusted for differences in underlying risk between the FH01 cohort and the control group of the UK Age Trial. This study is registered with the National Research Register, number N0484114809.
6710 women were enrolled between Jan 16, 2003, and Feb 28, 2007, and received yearly mammography for a mean of 4 years (SD 2) up until Nov 30, 2009; surveillance and reporting of cancers is still underway. 136 women were diagnosed with breast cancer: 105 (77%) at screening, 28 (21%) symptomatically in the interval between screening events, and three (2%) symptomatically after failing to attend their latest mammogram. Invasive tumours in the FH01 study were significantly smaller (p=0·0094), less likely to be node positive (p=0·0083), and of more favourable grade (p=0·0072) than were those in the control group of the UK Age Trial, and were significantly less likely to be node positive than were tumours in the Dutch study (p=0·012). Mean NPI score was significantly lower in the FH01 cohort than in the control group of the UK Age Trial (p=0·00079) or the Dutch study (p<0·0001). After adjustment for underlying risk, predicted 10-year mortality was significantly lower in the FH01 cohort (1·10%) than in the control group of the UK Age Trial (1·38%), with relative risk of 0·80 (95% CI 0·66-0·96; p=0·022).
Yearly mammography in women with a medium familial risk of breast cancer is likely to be effective in prevention of deaths from breast cancer.
有证据表明，在 40-49 岁的普通女性人群中，通过乳房 X 光筛查可以降低乳腺癌死亡率，但家族史的影响尚不清楚。我们旨在确定筛查是否会影响具有临床显著乳腺癌家族史的年龄小于 50 岁的女性的疾病分期和预期死亡率。
在 FH01 单臂研究中，来自英国 76 个中心的年龄在 50 岁以下的具有中度家族风险的女性被招募，并接受每年的乳房 X 光检查。未明确排除携带 BRCA 突变的女性，但在该组中很罕见。为了将 FH01 队列与未接受筛查的女性进行比较，使用了两个外部对照组：英国年龄试验的对照组（招募时年龄为 40-42 岁的 106,971 名女性，来自普通人群[即平均风险]，随访 10 年），以及荷兰乳腺癌家族史研究的对照组（癌症病例年龄为 25-77 岁，诊断时间为 1980-2004 年）。研究终点是侵袭性肿瘤的大小、淋巴结状态和组织学分级，以及根据诺丁汉预后指数（NPI）评分计算的估计死亡率，并根据 FH01 队列和英国年龄试验对照组之间的潜在风险差异进行了调整。这项研究在国家研究注册处注册，编号为 N0484114809。
2003 年 1 月 16 日至 2007 年 2 月 28 日期间共招募了 6710 名女性，直至 2009 年 11 月 30 日，她们平均每年接受一次乳房 X 光检查（SD 2），为期 4 年；仍在进行癌症的监测和报告。共诊断出 136 例乳腺癌：105 例（77%）在筛查中发现，28 例（21%）在筛查事件之间出现症状，3 例（2%）在未能进行最新乳房 X 光检查时出现症状。FH01 研究中的侵袭性肿瘤明显更小（p=0·0094），淋巴结阳性的可能性更小（p=0·0083），分级更有利（p=0·0072），与英国年龄试验对照组相比，淋巴结阳性的可能性更小（p=0·012）。FH01 队列的平均 NPI 评分明显低于英国年龄试验对照组（p=0·00079）或荷兰研究对照组（p<0·0001）。在调整潜在风险后，FH01 队列的 10 年预计死亡率（1.10%）明显低于英国年龄试验对照组（1.38%），相对风险为 0.80（95%CI 0.66-0·96；p=0·022）。
对于具有中等乳腺癌家族风险的女性，每年进行乳房 X 光筛查可能有助于预防乳腺癌死亡。
