Harada-Shoji Narumi, Suzuki Akihiko, Ishida Takanori, Zheng Ying-Fang, Narikawa-Shiono Yoko, Sato-Tadano Akiko, Ohta Rie, Ohuchi Noriaki
Department of Breast and Endocrine Surgical Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Department of Breast and Endocrine Surgery, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
JAMA Netw Open. 2021 Aug 2;4(8):e2121505. doi: 10.1001/jamanetworkopen.2021.21505.
Mammography has limited accuracy in breast cancer screening. Ultrasonography, when used in conjunction with mammography screening, is helpful to detect early-stage and invasive cancers for asymptomatic women with dense and nondense breasts.
To evaluate the performance of adjunctive ultrasonography with mammography for breast cancer screening, according to differences in breast density.
DESIGN, SETTING, AND PARTICIPANTS: This study is a secondary analysis of the Japan Strategic Anti-cancer Randomized Trial. Between July 2007 and March 2011, asymptomatic women aged 40 to 49 years were enrolled in Japan. The present study used data from cases enrolled from the screening center in Miyagi prefecture during 2007 to 2020. Participants were randomly assigned in a 1:1 ratio to undergo either mammography with ultrasonography (intervention group) or mammography alone (control group). Data analysis was performed from February to March 2020.
Ultrasonography adjunctive to mammography for breast cancer screening regardless of breast density.
Sensitivity, specificity, recall rates, biopsy rates, and characteristics of screen-detected cancers and interval breast cancers were evaluated between study groups and for each modality according to breast density.
A total of 76 119 women were enrolled, and data for 19 213 women (mean [SD] age, 44.5 [2.8] years) from the Miyagi prefecture were analyzed; 9705 were randomized to the intervention group and 9508 were randomized to the control group. A total of 11 390 women (59.3%) had heterogeneously or extremely dense breasts. Among the overall group, 130 cancers were found. Sensitivity was significantly higher in the intervention group than the control group (93.2% [95% CI, 87.4%-99.0%] vs 66.7% [95% CI, 54.4%-78.9%]; P < .001). Similar trends were observed in women with dense breasts (sensitivity in intervention vs control groups, 93.2% [95% CI, 85.7%-100.0%] vs 70.6% [95% CI, 55.3%-85.9%]; P < .001) and nondense breasts (sensitivity in intervention vs control groups, 93.1% [95% CI, 83.9%-102.3%] vs 60.9% [95% CI, 40.9%-80.8%]; P < .001). The rate of interval cancers per 1000 screenings was lower in the intervention group compared with the control group (0.5 cancers [95% CI, 0.1-1.0 cancers] vs 2.0 cancers [95% CI, 1.1-2.9 cancers]; P = .004). Within the intervention group, the rate of invasive cancers detected by ultrasonography alone was significantly higher than that for mammography alone in both dense (82.4% [95% CI, 56.6%-96.2%] vs 41.7% [95% CI, 15.2%-72.3%]; P = .02) and nondense (85.7% [95% CI, 42.1%-99.6%] vs 25.0% [95% CI, 5.5%-57.2%]; P = .02) breasts. However, sensitivity of mammography or ultrasonography alone did not exceed 80% across all breast densities in the 2 groups. Compared with the control group, specificity was significantly lower in the intervention group (91.8% [95% CI, 91.2%-92.3%] vs 86.8% [95% CI, 86.2%-87.5%]; P < .001). Recall rates (13.8% [95% CI, 13.1%-14.5%] vs 8.6% [95% CI, 8.0%-9.1%]; P < .001) and biopsy rates (5.5% [95% CI, 5.1%-6.0%] vs 2.1% [95% CI, 1.8%-2.4%]; P < .001) were significantly higher in the intervention group than the control group.
In this secondary analysis of a randomized clinical trial, screening mammography alone demonstrated low sensitivity, whereas adjunctive ultrasonography was associated with increased sensitivity. These findings suggest that adjunctive ultrasonography has the potential to improve detection of early-stage and invasive cancers across both dense and nondense breasts. Supplemental ultrasonography should be considered as an appropriate imaging modality for breast cancer screening in asymptomatic women aged 40 to 49 years regardless of breast density.
NIPH Clinical Trial Identifier: UMIN000000757.
乳腺钼靶摄影在乳腺癌筛查中的准确性有限。超声检查与乳腺钼靶摄影筛查联合使用时，有助于检测乳房致密和非致密的无症状女性的早期和浸润性癌症。
根据乳房密度差异，评估超声检查辅助乳腺钼靶摄影进行乳腺癌筛查的性能。
设计、设置和参与者：本研究是对日本战略抗癌随机试验的二次分析。2007年7月至2011年3月期间，日本招募了40至49岁的无症状女性。本研究使用了2007年至2020年期间从宫城县筛查中心登记的病例数据。参与者被随机分配为1:1比例，分别接受乳腺钼靶摄影联合超声检查（干预组）或单独接受乳腺钼靶摄影（对照组）。数据分析于2020年2月至3月进行。
无论乳房密度如何，超声检查辅助乳腺钼靶摄影进行乳腺癌筛查。
在研究组之间以及根据乳房密度对每种检查方式，评估敏感性、特异性、召回率、活检率以及筛查发现的癌症和间期乳腺癌的特征。
共纳入76119名女性，分析了来自宫城县的19213名女性（平均[标准差]年龄，44.5[2.8]岁）的数据；9705名被随机分配到干预组，9508名被随机分配到对照组。共有11390名女性（59.3%）乳房为不均匀致密或极度致密。在整个研究组中，共发现130例癌症。干预组的敏感性显著高于对照组（93.2%[95%置信区间，87.4%-99.0%]对66.7%[95%置信区间，54.4%-78.9%]；P<0.001）。在乳房致密的女性中观察到类似趋势（干预组与对照组的敏感性，93.2%[95%置信区间，85.7%-100.0%]对70.6%[95%置信区间，55.3%-85.9%]；P<0.001）以及乳房非致密的女性（干预组与对照组的敏感性，93.1%[95%置信区间，83.9%-102.3%]对60.9%[95%置信区间，40.9%-80.8%]；P<0.001）。干预组每1000次筛查的间期癌症发生率低于对照组（0.5例癌症[95%置信区间，0.1-1.0例癌症]对2.0例癌症[95%置信区间，1.1-2.9例癌症]；P=0.004）。在干预组中，单独通过超声检查发现的浸润性癌症发生率在乳房致密（82.4%[95%置信区间，56.6%-96.2%]对41.
