Breast cancer screening with digital breast tomosynthesis

Purpose

To give an overview of studies comparing full-field digital mammography (FFDM) and digital breast tomosynthesis (DBT) in breast cancer screening.

Materials and methods

The implementation of tomosynthesis in breast imaging is rapidly increasing world-wide. Experimental clinical studies of relevance for DBT screening have shown that tomosynthesis might have a great potential in breast cancer screening, although most of these retrospective reading studies are based on small populations, so that final conclusions are difficult to draw from individual reports. Several retrospective studies and three prospective trials on tomosynthesis in breast cancer screening have been published so far, confirming the great potential of DBT in mammography screening. The main results of these screening studies are presented.

Results

The retrospective screening studies from USA have all shown a significant decrease in the recall rate using DBT as adjunct to mammography. Most of these studies have also shown an increase in the cancer detection rate, and the non-significant results in some studies might be explained by a lack of statistical power. All the three prospective European trials have shown a significant increase in the cancer detection rate.

Conclusion

The retrospective and the prospective screening studies comparing FFDM and DBT have all demonstrated that tomosynthesis has a great potential for improving breast cancer screening. DBT should be regarded as a better mammogram that could improve or overcome limitations of the conventional mammography, and tomosynthesis might be considered as the new technique in the next future of breast cancer screening.

     

数字乳腺断层摄影与全数字化乳腺摄影对致密型乳腺病变诊断的初步对比研究

目的 研究数字乳腺断层摄影(DBT)与全数字化乳腺摄影(FFDM)对致密型乳腺病变特征的显示效果,以及FFDM检查、FFDM结合DBT检查诊断致密型乳腺病变的准确性,评价DBT诊断致密型乳腺病变的价值.方法 选择致密型乳腺患者134例,分别采用FFDM、FFDM结合DBT进行独立诊断,以病理诊断作为金标准,评价FFDM、FFDM结合DBT诊断致密型乳腺病变的准确性.比较FFDM和DBT显示的病变特征以及肿块型病变的最长径.结果 134例患者中,良性病变69例,恶性病变65例.65例恶性病变中,DBT和FFDM检出毛刺征分别为30例和14例.在69例良性病变中,DBT和FFDM检出肿物边缘清楚分别为46例和33例.DBT检查显示血管穿入征3例.在3型乳腺中,FFDM与DBT检查毛刺征的检出率比较,差异有统计学意义(P＜0.05);边缘清楚和血管征的检出率差异均无统计学意义(均P＜0.05).在层厚1 mm时,63.9％ (23/36)的DBT与FFDM显示钙化的效果相似,5.6％ (2/36)的DBT显示效果优于FFDM,30.6％ (11/36)显示效果差于FFDM;FFDM与DBT显示钙化的效果差异有统计学意义(P＜0.05).当改变层厚为1 cm时,二者显示钙化的效果差异无统计学意义(P＞0.05).DBT测量肿块型病变最长径为(2.46±1.64)cm,FFDM测量最长径为(2.58±1.62)cm,二者差异有统计学意义(P＜0.05).FFDM、FFDM结合DBT诊断病变的准确性分别为88.8％和91.8％.以病理诊断作为金标准,FFDM诊断的ROC曲线下面积(AUC)为0.887,FFDM结合DBT诊断的AUC值为0.918.结论 对致密型乳腺疾病的诊断,DBT在显示病变的形态特征和微小钙化方面,具有一定的优势.FFDM结合DBT对提高病变诊断的准确性并不显著.     

Digital breast tomosynthesis (3D mammography) for breast cancer screening and for assessment of screen-recalled findings: review of the evidence

Introduction: Digital breast tomosynthesis (DBT) addresses some of the limitations of digital mammography (DM) by reducing the effect of overlapping tissue. Emerging data have shown that DBT increases breast cancer (BC) detection and reduces recall in BC screening programs. Studies have also suggested that DBT improves assessment of screen-recalled findings.

Areas covered: Studies of DBT for population BC screening and those for assessment of screen-detected findings were reviewed to provide an up-to-date summary of the evidence on DBT in the screening setting. A systematic literature search was conducted for each of the topics; study-specific information and/or quantitative data on detection or accuracy were extracted and collated in tables.

Expert commentary: The evidence on DBT for BC screening reinforces that DBT integrated with DM increases cancer detection rates compared to DM alone, although the extent of improved detection varied between studies. The effect of DBT on recall rates was heterogeneous with substantial reductions evident noticeably in retrospective comparative studies. The evidence on DBT for workup was sparse and those studies had limitations related to design and methods. Even though the majority showed improved specificity using DBT compared with conventional imaging, there was little evidence on how DBT impacts assessment outcomes.     

数字乳腺断层融合X线摄影术前评估乳腺癌肿块大小的效能对比研究

背景与目的：全数字化乳腺摄影（full-field digital mammography,FFDM）的大规模使用可显著降低乳腺癌的死亡率,但对于致密型乳腺患者,其诊断灵敏度和特异度明显减低。本研究旨在对比数字乳腺断层融合X线摄影（digital breast tomosynthesis,DBT）与常规影像学检查术前评估乳腺癌肿块大小的效能。方法：回顾性分析2015年3月—2015年12月在复旦大学附属肿瘤医院就诊并经病理学检查证实为乳腺癌的136例患者,所有患者均行超声、FFDM、DBT和磁共振成像（magnetic resonance imaging,MRI）检查。选取每种检查均可测量最大径的肿块纳入本研究。由3名高年资放射诊断科医师分别测量可见肿块最大径,利用方差分析比较DBT、超声、FFDM及MRI与术后大体标本测量值之间的差异;利用Pearson相关系数分析各种检查与大体标本测量值之间的相关性,并应用配对t检验评价DBT术前评估肿块大小的能力。结果：136例患者共发现140枚肿块,排除26例患者选择先辅助化疗后再行手术,最后纳入研究的为114枚肿块。DBT及MRI测得肿瘤最大径与病理测量值之间差异无统计学意义（P均>0.05）;FFDM和超声与病理测量值相比差异有统计学意义（与FFDM相比：t=3.30,P=0.013 4;与超声相比：t=2.58,P=0.021 5）。DBT（r=0.81）、MRI测量值（r=0.84）与病理测量值的相关性显著高于超声（r=0.68）和FFDM组（r=0.69)。结论：DBT术前评估乳腺癌肿块大小的能力显著优于超声和FFDM,与MRI相似;DBT作为乳腺X线摄影新技术,在乳腺癌术前分期中有良好的应用前景。     

Differential detection by breast density for digital breast tomosynthesis versus digital mammography population screening: a systematic review and meta-analysis

Background We examined whether digital breast tomosynthesis (DBT) detects differentially in high- or low-density screens.Methods We searched six databases (2009–2020) for studies comparing DBT and digital mammography (DM), and reporting cancer detection rate (CDR) and/or recall rate by breast density. Meta-analysis was performed to pool incremental CDR and recall rate for DBT (versus DM) for high- and low-density (dichotomised based on BI-RADS) and within-study differences in incremental estimates between high- and low-density. Screening settings (European/US) were compared.Results Pooled within-study difference in incremental CDR for high- versus low-density was 1.0/1000 screens (95% CI: 0.3, 1.6; p = 0.003). Estimates were not significantly different in US (0.6/1000; 95% CI: 0.0, 1.3; p = 0.05) and European (1.9/1000; 95% CI: 0.3, 3.5; p = 0.02) settings (p for subgroup difference = 0.15). For incremental recall rate, within-study differences between density subgroups differed by setting (p < 0.001). Pooled incremental recall was less in high- versus low-density screens (−0.9%; 95% CI: −1.4%, −0.4%; p < 0.001) in US screening, and greater (0.8%; 95% CI: 0.3%, 1.3%; p = 0.001) in European screening.Conclusions DBT has differential incremental cancer detection and recall by breast density. Although incremental CDR is greater in high-density, a substantial proportion of additional cancers is likely to be detected in low-density screens. Our findings may assist screening programmes considering DBT for density-tailored screening.Subject terms: Cancer screening, Cancer imaging, Breast cancer     

醋酸染色肉眼观察在子宫颈癌筛查分流中的应用价值

目的:评价醋酸染色肉眼观察(VIA)在宫颈癌筛查中分流自我取样人乳头瘤病毒(HPV) DNA阳性人群的可行性及应用价值.方法:对2 500名河南省新密市25～65岁的妇女进行宫颈癌筛查.初次访视时每位妇女均接受了自我取样HPV DNA检测和VIA.任何筛查阳性及随机10％阴性的妇女进行第2次VIA和阴道镜检查.阴道镜下可见病变处直接活检;无可见病变但筛查阳性时行四象限随机活检+宫颈管搔刮术(ECC).以病理诊断为金标准.结果:最终有2 463名妇女纳入分析.目标人群自我取样HPV的阳性率为17.3％(427/2 463),检出CINⅡ+的灵敏度为89.2％(33/37),特异度为83.8％(2 032/2 426),阳性预测值(PPV)为7.7％(33/427).用VIA对自我取样HPV DNA阳性者进行分流,阴道镜转诊率由17.3％(427/2 463)降至2.5％(61/2 463),x2=304.7,P＜0.001;特异度和PPV可分别达到98.3％(2 384/2 426)(x2=350.0,P＜0.001)和31.2％(19/61),x2=30.7,P＜0.001,灵敏度为51.4％.结论:用VIA分流自我取样HPV DNA阳性妇女,可以显著提高宫颈癌筛查的特异度和PPV值,明显降低阴道镜转诊率,对于未绝经妇女,意义更为显著.这种分流方法可以有效节约卫生资源,有望成为宫颈癌筛查分流的一种新选择.     

数字乳腺断层融合X线成像技术对早期乳腺癌的诊断价值

目的 探讨数字乳腺断层融合X线成像技术(DBT)在乳腺癌早期诊断中的应用价值.方法 对150例临床检查可疑、乳腺超声诊断报告和数据系统(BI-RADS)0级或≥3级的病例,分别行乳腺X线摄影(DM)检查和DBT检查,并独立诊断.以病理诊断结果 为金标准,比较DM和DBT对早期乳腺癌及致密型乳腺癌的诊断效能.结果以病理诊断结果为金标准,DBT与DM诊断早期乳腺癌的灵敏度分别为86.6％和74.2％,特异度分别为96.2％和81.1％,准确度分别为90.0％和76.7％,DBT对早期乳腺癌的诊断效能优于DM,差异均有统计学意义(P﹤0.05).以病理诊断结果为金标准,DBT与DM对致密型乳腺癌诊断的灵敏度分别为94.6％和70.3％,特异度分别为92.9％和64.3％,准确度分别为93.8％和67.7％,DBT对致密型乳腺癌的诊断效能优于DM,差异均有统计学意义(P﹤0.05).结论 DBT能提高早期乳腺癌尤其是致密型乳腺癌的检出率,诊断效能优于DM.     

The emerging role of breast tomosynthesis

Digital breast tomosynthesis (DBT) is a new modality that aids in breast cancer detection. It is a pseudo-three-dimensional digital mammography imaging system that produces a series of 1-mm-slice images with multiple very low-dose X-ray projections to reveal the inner architecture of the breast after eliminating interference from overlapping breast tissue. This review article provides an overview of the current and potential use of DBT. The illustrations and discussion are based on our experience with the Selenia Dimensions (Hologic, USA) DBT system approved by the US Food and Drug Administration.     

Performance of breast cancer screening using digital breast tomosynthesis: results from the prospective population-based Oslo Tomosynthesis Screening Trial

Purpose

Digital breast tomosynthesis (DBT) has the potential to overcome limitations of conventional mammography. This study investigated the effects of addition of DBT on interval and detected cancers in population-based screening.

Methods

Oslo Tomosynthesis Screening Trial (OTST) was a prospective, independent double-reading trial inviting women 50–69 years biennially, comparing full-field digital mammography (FFDM) plus DBT with FFDM alone. Performance indicators and characteristics of screen-detected and interval cancers were compared with two previous FFDM rounds.

Results

24,301 consenting women underwent FFDM + DBT screening over a 2-year period. Results were compared with 59,877 FFDM examinations during prior rounds. Addition of DBT resulted in a non-significant increase in sensitivity (76.2%, 378/496, vs. 80.8%, 227/281, p = 0.151) and a significant increase in specificity (96.4%, 57229/59381 vs. 97.5%, 23427/24020, p < .001). Number of recalls per screen-detected cancer decreased from 6.7 (2530/378) to 3.6 (820/227) with DBT (p < .001). Cancer detection per 1000 women screened increased (6.3, 378/59877, vs. 9.3, 227/24301, p < .001). Interval cancer rate per 1000 screens for FFDM + DBT remained similar to previous FFDM rounds (2.1, 51/24301 vs. 2.0, 118/59877, p = 0.734). Interval cancers post-DBT were comparable to prior rounds but significantly different in size, grade, and node status from cancers detected only using DBT. 39.6% (19/48) of interval cancers had positive nodes compared with only 3.9% (2/51) of additional DBT-only-detected cancers.

Conclusions

DBT-supplemented screening resulted in significant increases in screen-detected cancers and specificity. However, no significant change was observed in the rate, size, node status, or grade of interval cancers.ClinicalTrials.gov: NCT01248546.

     

A prospective study comparing digital breast tomosynthesis with digital mammography in surveillance after breast cancer treatment

BackgroundAlthough the benefit of adjunct digital breast tomosynthesis (DBT) is established in population screening, its benefit in surveillance after breast cancer treatment is not well defined. We prospectively evaluated whether the addition of DBT to digital mammography (DM) reduced the rate of indeterminate findings compared to DM alone in patients after breast cancer treatment.MethodsPatients had both DM and DBT for routine surveillance. Two-dimensional synthesised mammogram (SM) was generated for each patient from DBT data. DM, SM, and DBT images were read for each patient by one of four radiologists credentialed for DBT. We compared the rates of indeterminate findings between DM + DBT with DM alone in patients with a range of breast densities and between DM and SM.ResultsA total of 618 patients and 1069 breasts were analysed. The rates of indeterminate findings for DM + DBT versus DM alone were 10.5% and 13.1%, respectively (p = 0.018). In breasts treated with surgery and radiotherapy (n = 558), the corresponding rates of indeterminate findings were 4.9% and 6.9%, respectively (p = 0.039). The rate of indeterminate findings for DM + DBT increased with increasing breast density (p = 0.019). There was no significant difference in the rates of indeterminate findings between DM and SM (13.1% versus 11.5%, p = 0.1).ConclusionThe addition of DBT to DM reduced the rate of indeterminate findings in surveillance of patients after breast cancer treatment. Further research is required to confirm whether DBT and SM could replace DM for patients undergoing surveillance.     

Prospective study of screening for stomach cancer in Japan

Although screening for stomach cancer is a widespread community service in Japan, the benefits of the screening program remain unclear. Our study investigated prospectively the relation between participation in stomach-cancer screening during the past 12 months and subsequent deaths. Data was derived from the Japan Collaborative Cohort Study, in which 480 stomach-cancer deaths were identified during an 8-year follow-up period. Cox proportional hazard regression was used to estimate the relative risk of death from stomach cancer and that from other causes while adjusting for potential confounding factors. In men, screening participation was associated significantly with a reduced risk of death from stomach cancer (relative risk [RR] = 0.54; 95% confidence interval [CI] = 0.41-0.70). The extent of the risk reduction was greater than potential health selection (for deaths other than stomach, RR = 0.71). The adjustment for potential confounding variables, however, attenuated the difference in risk of death (stomach cancer, RR = 0.65; other causes, RR = 0.71). In women, the magnitude of the association between screening participation and death from stomach cancer (RR = 0.74; 95% CI = 0.52-1.07) was equal to that for deaths from non-stomach cancers (RR = 0.74). Subgroup analysis showed that women with a parental history of stomach cancer had a reduced risk of death from stomach cancer associated with screening (RR = 0.32; 95% CI = 0.12-0.87). The present results underline the potential for selection bias in observational studies, and thus it remains an open question whether screening for stomach cancer is effective.     

双模式数字乳腺体层合成成像对乳腺疾病的诊断价值

背景与目的：全数字化乳腺X线摄影（full-field digital mammography,FFDM）可显著降低乳腺癌的死亡率,但作为一种二维成像方式,对于致密型乳腺构成分类患者,其诊断灵敏度和特异度明显较低。探讨数字乳腺体层合成成像（digital breast tomosynthesis,DBT）结合FFDM对乳腺病变的鉴别诊断价值以及高分辨率扫描（high-resolution,HR）模式（扫描角度为40°,DBT-HR）和标准扫描（standard,ST）模式（扫描角度为15°,DBT-ST）诊断乳腺病变的价值。方法：前瞻性收集2016年7月—9月经临床或超声检查怀疑有乳腺异常病变,且经穿刺活检或术后病理学检查证实的175例女性乳腺疾病患者,行FFDM和DBT检查,随机进入DBT-HR组和DBT-ST组,对FFDM图像和DBT结合FFDM图像进行分析。参照2013版《乳腺影像报告和数据系统》（Breast Imaging Reporting and Data System,BI-RADS）分类标准,以病理学检查结果为金标准,采用受试者工作特征（receiver operating characteristic,ROC）曲线分析FFDM和DBT结合FFDM的诊断效能,根据不同的乳腺构成分类分别分析DBT-HR和DBT-ST的灵敏度和特异度。结果：175例患者共检出181个病灶,良性病灶50个,恶性病灶131个,所有入组病例的FFDM和FFDM结合DBT的灵敏度为81.92%和91.15%,特异度为77.45%和87.25%,两种方法的ROC曲线的曲线下面积（area under curve,AUC）差异有统计学意义（0.88 vs 0.94,Z值=5.37,P<0.01）。随机分入DBT-HR组病灶86个而DBT-ST组病灶95个。DBT-HR组FFDM和DBT主要征象表现一致率为83.14%,仅DBT可见率为3.49%,DBT-ST组FFDM和DBT主要征象表现一致率为92.63%,仅DBT可见率为0.53%。致密型乳房在结合DBT后灵敏度和特异度提高均较非致密型乳房明显,尤其是HR组致密型乳房灵敏度（18.72%）和ST组的致密型乳房的特异度（14.28%）均有所提高。结论：FFDM结合DBT的诊断效能优于FFDM,且DBT-HR优于DBT-ST,尤其是对致密型乳房的诊断。     

Validation of a DNA methylation HPV triage classifier in a screening sample

High‐risk human papillomavirus (hrHPV) DNA tests have excellent sensitivity for detection of cervical intraepithelial neoplasia 2 or higher (CIN2+). A drawback of hrHPV screening, however, is modest specificity. Therefore, hrHPV‐positive women might need triage to reduce adverse events and costs associated with unnecessary colposcopy. We compared the performance of HPV16/18 genotyping with a predefined DNA methylation triage test (S5) based on target regions of the human gene EPB41L3, and viral late gene regions of HPV16, HPV18, HPV31 and HPV33. Assays were run using exfoliated cervical specimens from 710 women attending routine screening, of whom 38 were diagnosed with CIN2+ within a year after triage to colposcopy based on cytology and 341 were hrHPV positive. Sensitivity and specificity of the investigated triage methods were compared by McNemar's test. At the predefined cutoff, S5 showed better sensitivity than HPV16/18 genotyping (74% vs 54%, P = 0.04) in identifying CIN2+ in hrHPV‐positive women, and similar specificity (65% vs 71%, P = 0.07). When the S5 cutoff was altered to allow equal sensitivity to that of genotyping, a significantly higher specificity of 91% was reached (P < 0.0001). Thus, a DNA methylation test for the triage of hrHPV‐positive women on original screening specimens might be a valid approach with better performance than genotyping.     

Detectability comparison of modes in dual-mode digital breast tomosynthesis

Background

The objectives of this study were: (1) to evaluate the detectability of full-field digital mammography (FFDM) plus dual-mode digital breast tomosynthesis (DBT) and compare it with that of FFDM alone and (2) to compare the detectability of high-resolution-mode (HR mode used with 40°-angle imaging, 100-µm pixel size, and higher dose) DBT with that of standard-mode (ST mode used with 15°-angle imaging, 150-µm pixel size, and lower dose) DBT for diagnostic evaluation.

Materials

The local Institutional Review Board approved this retrospective study of two different sets of cases. All participants gave written informed consent. FFDM and DBT images of 471 women who were recalled were acquired between August 2013 and October 2014. HR mode and ST mode were applied to 155 breasts and 157 breasts, respectively. The cases of both modes were selected randomly. Eight radiologists interpreted the images. The detectability for recall cases and for follow cases, and area under the receiver operating characteristic curve (AUC) were calculated.

Results

Adding DBT to FFDM significantly increased the detectability for recall cases and AUC relative to those of FFDM alone (HR mode 8.9 %; 95 % confidence interval (CI) 5.7, 15.0 %; P = 0.013 and 4.9 %; 95 % CI 2.1, 7.7 %; P = 0.001; ST mode 8.3 %; 95 % CI 4.1, 12.1 %; P = 0.007 and 2.9 %; 95 % CI 0.5, 5.3 %; P = 0.02), whereas the detectability for follow cases did not significantly differ. The AUC increase was significantly higher in HR mode than in ST mode (1.5 %; 95 % CI 0.5, 3.7 %; P = 0.023).

Conclusion

Adding HR-mode or ST-mode DBT to FFDM significantly improved the detectability for diagnostic evaluation case.

     

A study of the impact of adding HPV types to cervical cancer screening and triage tests

Use of human papillomavirus (HPV) testing in cervical cancer prevention is increasing rapidly. A DNA test for 13 HPV types that can cause cervical cancer is approved in the United States for co-screening with cytology of women >or=30 years old and for triage of women of all ages with equivocal cytology. However, most infections with HPV are benign. We evaluated trade-offs between specificity and sensitivity for approximately 40 HPV types in predicting cervical intraepithelial neoplasia 3 and cancer in two prospective studies: a population-based screening study that followed 6196 women aged 30-94 years from Costa Rica for 7 years and a triage study that followed 3363 women aged 18-90 years with equivocal cytology in four U.S. centers for 2 years. For both screening and triage, testing for more than about 10 HPV types decreased specificity more than it increased sensitivity. The minimal increases in sensitivity and in negative predictive value achieved by adding HPV types to DNA tests must be weighed against the projected burden to thousands of women falsely labeled as being at high risk of cervical cancer.