MRI remains strongly superior to mammography over the long term in screening women who are at increased risk of developing breast cancer, according to a study published online Nov. 16 in the Journal of Clinical Oncology.

The advantage in sensitivity was highly significant for BRCA1 mutation carriers, but not for those who carried BRCA2 mutations and were more likely to present with ductal carcinoma in situ (DCIS).

Previous research showed that in the short term, MRI was approximately twice as sensitive as mammography in detecting breast cancer among women susceptible to the disease, and most guidelines now recommend MRI screening in those who carry BRCA1 or BRCA2 mutations. However, there is no consensus on the screening protocol for other risk groups, few studies have assessed BRCA1 carriers separately from BRCA2 carriers, and until now no studies have evaluated longer-term screening results, said Dr. Adriana J. Rijnsburger of Erasmus University Medical Center, Rotterdam, the Netherlands, and her associates.

To address these issues, the investigators enlarged and extended the Dutch MRI Screening Study (MRISC) and report their findings after following 2,157 women at six cancer or academic centers for 5 years.

The study subjects, aged 25-75 years at enrollment, had never had breast cancer but were at increased risk because they carried either the BRCA1 or BRCA2 mutation (raising their cumulative lifetime risk of developing breast cancer to 50%-85%), had a high-risk family history (raising their cumulative lifetime risk of developing breast cancer to 30%-50%), or had a moderate-risk family history (raising their cumulative lifetime risk of developing breast cancer to 15%-30%). They underwent biannual clinical breast examination and annual mammography and MRI.

During 5 years of follow-up, 97 breast cancers developed in 94 women, including 78 (80%) invasive tumors and 19 (20%) cases of DCIS.

Sensitivity at detecting breast cancer was 71% with MRI, significantly greater than the 41% sensitivity of mammography. When only invasive breast cancers were considered, MRI sensitivity increased to 78%, while mammography’s sensitivity decreased to 36%.

When the analysis was restricted only to women who carried genetic mutations, the sensitivity of MRI (67%) was “strikingly” higher than that of mammography (25%) for BRCA1 carriers. In contrast, MRI sensitivity (69%) was only slightly higher than mammography’s sensitivity (62%) in BRCA2 carriers.

This difference can be explained, at least in part, by the higher proportion of DCIS in BRCA2 than in BRCA1 carriers; mammography was much more sensitive in detecting DCIS (69%) than in detecting invasive tumors (36%).

The specificity of the two screening methods was not significantly different.

Overall, 43% of breast cancers were detected by MRI only. This included 46% of the cancers in BRCA1 carriers, 31% in BRCA2 carriers, 41% in women with a high-risk family history, and 47% in the women with a moderate-risk family history, Dr. Rijnsburger and her colleagues said (J. Clin. Oncol. 2010 Nov. 16; doi:10.1200/JCO.2009.27.2294).

These findings “support the recommendation of the American Cancer Society to use annual MRI screening not only for BRCA1/2 mutation carriers, but for all women with an approximately 20%-25% or greater cumulative lifetime risk of breast cancer due to a familial predisposition,” they noted, with the caveat that cost effectiveness should be evaluated separately in all risk groups.

This also was the first prospective study of screening in this at-risk patient population to report mortality data, the researchers added.

Five women, all BRCA1/2 mutation carriers, developed distant metastases, and four of them died during follow-up. Two of the women who died had had a favorable tumor stage at diagnosis. This finding underscores the need for clinicians to avoid guaranteeing that all breast cancer deaths can be prevented by early detection via screening, Dr. Rijnsburger and her associates said.

Survival was 84% in the women with BRCA1 mutations and invasive cancer, and 93% in those with BRCA2 mutations and invasive cancer. Survival was 100% in the other at-risk groups.

BRCA1-associated tumors “behaved completely differently” from BRCA2-associated tumors. They developed at a younger patient age, were not detected as well on mammography, were more likely to develop during the interval between screenings, were more likely to be invasive, and were larger at diagnosis.

This indicates that the current screening schedule for BRCA1 carriers may need to be modified, perhaps by increasing MRI screening to twice rather than once yearly, Dr. Rijnsburger and her colleagues said.

“The investigators have conducted the largest such trial of MRI screening in high-risk individuals, and their new report that MRI screening appears to be preferentially useful in BRCA1 mutation carriers as compared to BRCA2 has potentially practice-changing implications,” Dr. Andrew D. Seidman said in an American Society of Clinical Oncology (ASCO) press statement accompanying the online report of Dr. Rijnsburger’s study.

This study was supported by the Dutch government and the Cancer Genomics Center in the Netherlands. The investigators reported having no financial conflicts of interest.

Copyright (c) 2010 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

据11月16日在线发表于《临床肿瘤学杂志》(the Journal of Clinical Oncology)的一项研究，应用磁共振成像(MRI)对乳腺癌高危患者进行筛检所取得的长期效果显著优于乳腺X线摄影检查。

 

既往研究表明，应用MRI对乳腺癌高危患者进行筛检在短期内的灵敏度约为乳腺X线摄影检查的2倍，但目前几乎没有对BRCA1/2携带者进行单独评估或对筛检长期效果进行评估的相关研究。

 

研究者对荷兰MRI筛检研究(MRISC)纳入的2,157例女性受试者(分别来自6个肿瘤或医学中心)进行了为期5年的随访。受试者的年龄在25~75岁之间，之前未患乳腺癌，但该病发病风险较高(BRCA1或BRCA2突变携带者，其乳腺癌终生累积发病风险增高50%~85%)，或存在高、中等级风险乳腺癌家族史(其乳腺癌终生累积发病风险分别增高30%~50%或15%~30%)。受试者每年分别接受2次乳腺临床检查和1次乳腺X线摄影及MRI检查。

 

在5年随访期中，94例患者发生乳腺癌(肿瘤共计97处)，其侵袭性肿瘤和DCIS分别为78处(80%)和19处(20%)。MRI筛检乳腺癌的灵敏度(71%)显著高于乳腺X线摄影(41%)。MRI和乳腺X线摄影对侵袭性乳腺癌的筛检灵敏度分别为78%和36%。MRI对BRCA1携带者的筛检灵敏度(67%)显著高于乳腺X线摄影(25%)，但对BRCA2携带者的筛检灵敏度(69%)仅略高于乳腺X线摄影(62%)。乳腺X线摄影在筛检DCIS时的灵敏度(69%)显著高于侵袭性肿瘤(36%)，鉴于BRCA2携带者DCIS发病比例较高，故其更适用于这类患者。两种筛检方法的特异度无显著差别。

 

单用MRI筛检乳腺癌的成功率为43%，其对BRCA1和BRCA2携带者筛检成功率分别为46%和31%，对存在高、中等级风险乳腺癌家族史患者的筛检成功率分别为41%和47%。5例BRCA1/2女性携带者出现肿瘤远处转移，4例在随访期间死亡(2例在病情确诊时肿瘤并未转移)。这表明，早期发现无法确保患者日后一定存活，医生应避免做出此类承诺。BRCA1 和BRCA2携带女性罹患侵袭性肿瘤的生存率分别为84%和93%。其他风险组患者生存率为100%。

 

美国癌症学会曾建议将MRI筛检用于所有乳腺癌高危患者，而不局限于BRCA1/2突变携带者，但必须首先对不同风险组患者(终生累积风险在20%~25%之间甚至更高)应用该筛检的成本效益比进行单独评估。鉴于BRCA1携带者发病年龄早，肿瘤恶性度高，使用乳腺X线摄影无法检出且更有可能在两次筛查间隙中发病，应对BRCA1携带者的现行筛检流程进行修正，如将MRI筛检频率增高至1年2次。

 

本研究由荷兰政府和荷兰肿瘤基因组学研究中心赞助。研究者表示无经济利益冲突。

 

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