A comparison between digital breast tomosynthesis and full-field digital mammography for the detection of breast cancers

Purpose

To evaluate interobserver agreement in full-field digital mammography (FFDM) and digital breast tomosynthesis (DBT) in terms of both lesion detection and characterization, and to evaluate the cancer detection rate of standard two-view FFDM compared to various combinations of DBT.

Materials and methods

Thirty-five women (mean age 59.7; range 50–80 years) with 37 breast cancers who underwent both two-view DBT and two-view FFDM were included. DBT images were obtained using an investigational prototype. We performed interobserver agreement analyses using kappa (k) statistics. The cancer detection rate of various combinations of DBT compared to standard two-view FFDM was estimated using a generalized estimation equation.

Results

There was fair to moderate agreement on detectability (k = 0.59–0.62) in both views of FFDM and DBT, while fair to substantial agreement was found for lesion location (k = 0.52–0.84) and fair to moderate agreement for lesion type (k = 0.46–0.70) and BI-RADS final assessment (k = 0.48–0.69). In generalized estimation equations, standard two-view FFDM was inferior to any combination of DBT. The detection rate ratio was significantly higher in the combined four views of DBT and FFDM compared to standard FFDM (p < 0.046).

Conclusion

Our study showed good agreement in lesion detection and characterization between FFDM and DBT images. Our findings also demonstrated that combining DBT and FFDM is superior in detecting cancer compared to standard FFDM.

     

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.

     

Diagnostic performance of digital breast tomosynthesis and full-field digital mammography with new reconstruction and new processing for dose reduction

Background

The main barrier to adoption of digital breast tomosynthesis (DBT) plus full-field digital mammography (FFDM) is radiation exposure dose. The purpose of this study was to evaluate the diagnostic performance of DBT plus FFDM, both with newly developed technology (nd), at a dose comparable to that of the conventional FFDM alone.

Methods

Nine hundred and thirteen participants were recruited from May 2014 to January 2016 consecutively. For each subject, the exposure setting for DBT(nd) + FFDM(nd) was also used for the conventional FFDM alone. Retrospective reader studies were performed: DBT(nd) + FFDM(nd) (142 cases, including 42 cancer cases) and conventional FFDM (258 cases, including 87 cancer cases). Eight radiologists provided Japanese categorizations and probability of malignancy independently. Diagnostic performance was assessed by comparing sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). Two-sided P values were calculated.

Results

DBT(nd) + FFDM(nd) showed sensitivity and AUC significantly increased over the conventional FFDM (85.4 vs. 80.3%, P = 0.015 and 90.9 vs. 88.3%, P = 0.049) and specificity did not significantly increase (89.6 vs. 88.4%, P = 0.52). The mean glandular dose (MGD) difference of DBT(nd) + FFDM(nd) and conventional FFDM was not significant (difference ? 0.11 mGy, P = 0.08).

Conclusions

In this study population, DBT plus FFDM, both with newly developed technology, provided diagnostic performance improved over the conventional FFDM alone, even at comparable MGD.

     

Clinical implementation of synthesized mammography with digital breast tomosynthesis in a routine clinical practice

Background

Most published studies evaluating digital breast tomosynthesis (DBT) included a separate 2-dimensional full-field digital mammogram (FFDM) for DBT screening protocols, increasing radiation from screening mammography. Synthesized mammography (SM) creates a 2-dimensional image from the DBT source data, and if used in place of FFDM, it reduces radiation of DBT screening. This study evaluated the implementation of SM + DBT in routine screening practice in terms of recall rates, cancer detection rates (CDR), % of minimal cancers, % of node-positive cancers, and positive predictive values (PPV).

Materials and methods

A multivariate retrospective institutional analysis was performed on 31,979 women who obtained screening mammography (10/2013–12/2015) with cohorts divided by modality (SM + DBT, FFDM + DBT, and FFDM). We adjusted for comparison mammograms, age, breast density, and the interpreting radiologist. Recall type was analyzed for differences (focal asymmetry, asymmetry, masses, calcifications, architectural distortion).

Results

SM + DBT significantly decreased the recall rate compared to FFDM (5.52 vs. 7.83%, p < 0.001) with no differences in overall CDR (p = 0.66), invasive and/or in situ CDR, or percentages of minimal and node-negative cancers. PPV1 significantly increased with SM + DBT relative to FFDM (9.1 vs. 6.2%, p = 0.02). SM + DBT did not differ significantly in recall rate or overall CDR compared to FFDM + DBT. There were statistically significant differences in certain findings recalled by screening modality (e.g., focal asymmetries).

Conclusions

SM + DBT reduces false positives compared to FFDM, while maintaining the CDR and other desirable audit outcome data. SM + DBT is more accurate than FFDM alone, and is a desirable alternative to FFDM + DBT, given the added benefit of radiation reduction.

     

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.

     

Digital mammography versus digital breast tomosynthesis for detection of breast cancer in the intraoperative specimen during breast-conserving surgery

Purpose

To compare the diagnostic ability of specimen radiography using digital mammography (DM) and digital breast tomosynthesis (DBT) for detecting breast cancer and evaluating its extension in the intraoperative specimen.

Methods

Sixty-five specimens from 65 women (median 62 years; range 34–86) obtained during breast-conserving surgery were prospectively investigated. Specimens underwent DM (25–40 kVp, 12–322 mA s) and DBT (25–34 kVp, 13–137 mA) in two orthogonal planes, anteroposterior (AP) and latero-lateral (LL). Images were interpreted by a radiologist to detect invasive lesions and their extensive intraductal components (EIC) or ductal carcinomas in situ (DCIS); afterwards, they were compared with histopathological findings.

Results

In AP views, 96 % of the invasive lesions were detected by both the methods. Of the EICs, 55 and 65 % were detected by DM and DBT, respectively (P = 0.61). Of the DICSs, 31 and 38 % were detected by DM and DBT, respectively (P > 0.99). In LL views, 71 and 13 % of the invasive lesions were detected by DBT and DM, respectively (P < 0.0001). Of the EICs, 42 and 10 % were detected by DBT and DM, respectively (P = 0.0078). Of the 13 DCISs, 42 and 8 % were detected by DBT and DM, respectively (P = 0.32). The whole lesion and contour could be delineated in 45 % by DBT and in 6.2 % by DM (P < 0.0001).

Conclusions

DBT could detect breast cancer more accurately than DM in LL views, indicating its potential to more precisely diagnose vertical invasion.

     

Comparison of synthetic mammography,reconstructed from digital breast tomosynthesis,and digital mammography: evaluation of lesion conspicuity and BI-RADS assessment categories

Purpose

To compare the interpretive performance of synthetic mammography (SM), reconstructed from digital breast tomosynthesis (DBT), and full-field digital mammography (FFDM) in a diagnostic setting, covering different conditions of breast density and mammographic signs.

Methods

A retrospective analysis was conducted on 231 patients, who underwent FFDM and DBT (from which SM images were reconstructed) between September 2014–September 2015. The study included 250 suspicious breast lesions, all biopsy proven: 148 (59.2%) malignant and 13 (5.2%) high-risk lesions were confirmed by surgery, 89 (35.6%) benign lesions had radiological follow-up. Two breast radiologists, blinded to histology, independently reviewed all cases. Readings were performed with SM alone, then with FFDM, collecting data on: probability of malignancy for each finding, lesion conspicuity, mammographic features and dimensions of detected lesions.

Results

Agreement between readers was good for BI-RADS classification (Cohen’s k-coefficient = 0.93 ± 0.02) and for lesion dimension (Wilcoxon’s p = 0.76). Visibility scores assigned to SM and FFDM for each lesion were similar for non-dense and dense breasts, however, there were significant differences (p = 0.0009) in distribution of mammographic features subgroups. SM and FFDM had similar sensitivities in non-dense (respectively 94 vs. 91%) and dense breasts (88 vs. 80%) and for all mammographic signs (93 vs. 87% for asymmetric densities, 96 vs. 75% for distortion, 92 vs. 85% for microcalcifications, and both 94% for masses). Based on all data, there was a significant difference in sensitivity for SM (92%) vs. FFDM (87%), p = 0.02, whereas the two modalities yielded similar results for specificity (SM: 60%, FFDM: 62%, p = 0.21).

Conclusions

SM alone showed similar interpretive performance to FFDM, confirming its potential role as an alternative to FFDM in women having tomosynthesis, with the added advantage of halving the patient’s dose exposure.

     

Non-calcified ductal carcinoma in situ of the breast: comparison of diagnostic accuracy of digital breast tomosynthesis,digital mammography,and ultrasonography

Background

To retrospectively compare the diagnostic accuracy of digital breast tomosynthesis (DBT), digital mammography (DM), and ultrasonography (US) in non-calcified ductal carcinoma in situ (DCIS, include DCIS with micro-invasion).

Patients and methods

Ninety-eight patients with non-calcified DCIS (include DCIS with micro-invasion) were enrolled in our study. Breast carcinoma in situ was confirmed by surgical pathologic evaluation. Our Institutional Review Board granted approval and the participating women provided written informed consent. The imaging findings were evaluated according to the Breast Imaging Reporting and Data System (BI-RADS) of the American College of Radiology (ACR) by comparing the differences in the detection rate and diagnostic accuracy among the three techniques in all cases, in dense breasts, and in non-dense breasts.

Results

The detection rates of DBT, DM, and US for non-calcified DCIS in all cases were 83.7, 68.4, and 94.9%, respectively, and in patients with dense breasts were 81.2, 63.8, and 95.0%. The detection rate of US was higher than DBT, which, in turn, was higher than DM both in all cases and in dense breasts. Pairwise comparisons among the three techniques showed that the differences were statistically significant (P = 0.000 and P = 0.000, respectively). The experts identified a case as abnormal for all criteria (BI-RADS score of 4B-5) in 68.4% of ratings using DBT, 43.9% of ratings using DM, and 66.3% of ratings using US; for dense breasts, the positive identification rates were 62.5% of ratings using DBT, 41.2% of ratings using DM, and 61.2% of ratings using US. The diagnostic accuracy of DBT and US was significantly higher than that of DM in all cases (P = 0.001 and P = 0.006, respectively) and in dense breasts (P = 0.007 and P = 0.011, respectively). The diagnostic accuracy of DBT was slightly higher than US in all cases and in dense breasts, but the difference was not statistically significant (P = 0.761 and P = 0.871, respectively). By DBT, most non-calcified cases of DCIS presented as a mass lesion (54.9%) with an irregular shape (46.7%), indistinct margin (53.3%), and isodense composition (71.1%). Using US, 72 of 93 patients (77.4%) were shown to have a mass. Most mass lesions had an irregular shape (83.3%), indistinct margin (55.5%), and parallel the skin (82.8%).

Conclusion

DBT and US gave better detection rates and diagnostic accuracy for non-calcified DCIS compared with DM in all cases and in dense breasts. The detection rate of DBT was lower than that of US in all cases and in dense breasts. The diagnostic accuracy of DBT was slightly higher than that of US in all cases and in dense breasts, but the difference was not statistically significant. Imaging findings for non-calcified DCIS were relatively non-specific.

     

Reducing chemotherapy use in clinically high-risk,genomically low-risk pN0 and pN1 early breast cancer patients: five-year data from the prospective,randomised phase 3 West German Study Group (WSG) PlanB trial

Purpose

To determine whether BPE in preoperative breast MRI influences patients’ recurrence-free survival (RFS).

Methods

Between February 2010 and December 2011, 804 consecutive women with invasive breast cancer who had undergone preoperative breast MRI and curative cancer surgery were identified. BPE was visually graded by two reviewers. We determined the correlation between BPE grade and other clinicopathological variables, including age, adjuvant therapy, menopausal status, histologic grade, T stage, N stage, lymphovascular invasion, molecular subtype, surgical margin status, and mammographic density. A Cox proportional hazards model was used to analyze the effects of clinicopathological variables and radiological findings (BPE grade, mammographic density) on RFS.

Results

High BPE was associated with premenopausal status (Ps < 0.0001), higher mammographic density (Ps < 0.0001), progesterone receptor positivity (Ps = 0.039, 0.007, respectively), presence of lymphovascular invasion (Ps = 0.008, 0.001, respectively), and close surgical margin (Ps < 0.0001). Recurrences were observed in 75 patients after a mean follow-up period of 61.8 months (range 4–81 months). Non-minimal BPE grade (RFS hazard ratio = 3.086, P = 0.003 for reader 1; RFS hazard ratio = 2.221, P = 0.075 for reader 2) and T3 stage were associated with worse outcomes in postmenopausal women. In premenopausal women, non-minimal BPE grade by readers 1 and 2 did not affect the patients’ outcomes.

Conclusions

Increased BPE on preoperative breast MRI in postmenopausal women has potential as a predictor of poor RFS.

     

Outcome of triple negative breast cancer: comparison of sporadic and BRCA1-associated cancers

The majority of breast cancers developing in BRCA1 mutation carriers are triple negative breast cancers (TNBC), an aggressive subtype that accounts for 15–20 % of sporadic breast cancer. We compare the clinical outcome and sites of relapse of TNBC in BRCA1 mutation carriers and non-carriers who received adjuvant chemotherapy. Women with stage I–III TNBC who had BRCA1 testing within 36 months of diagnosis and received adjuvant chemotherapy were identified from clinical databases at two academic institutions. Sites of relapse, freedom from distant metastasis (FFDM), and breast cancer-specific survival (BCSS) were determined. RCA1 carriers (n = 89) were significantly younger at diagnosis (P < 0.0001) than non-carriers (n = 175). FFDM at 5 years was 80.5 % for carriers and 76.9 % for non-carriers; with median follow-up of 55 months, hazard ratio (HR) was 0.90, P = 0.71. Sites of recurrence, including brain, did not differ significantly. BCSS at 5 years was 88.1 % for carriers and 81.4 % for non-carriers; HR 0.60; P = 0.15 at 55 months follow-up. BRCA1 carriers who underwent oophorectomy had a significantly lower rate of death from TNBC, with an adjusted HR of 0.30 (95 % CI 0.10–0.94). Adjusting for age, oophorectomy, and prophylactic mastectomy, BRCA1 mutation status was not an independent predictor of survival (HR 2.1; P = 0.13). BRCA1 mutation carriers with TNBC had similar survival rates and sites of recurrence to non-carriers after treatment with conventional chemotherapy. Carriers who underwent oophorectomy had a significantly lower rate of breast cancer-related death; this finding should be studied further in all women with TNBC.     

数字乳腺断层融合X线摄影与常规影像学检查诊断效能的对比研究

背景与目的:乳腺癌已成为女性最常见的恶性肿瘤,乳腺X线摄影新技术的出现对乳腺癌诊断起重要作用;该研究旨在对比数字乳腺断层融合X线摄影(digital breast tomosynthesis,DBT)与常规影像学检查诊断乳腺良、恶性病变的效能.方法:收集2015年3月—2015年12月在复旦大学附属肿瘤医院就诊且经临床或超声检查怀疑乳腺病变的227例患者.所有患者均行B超、全屏数字乳腺X线摄影(full-field digital mammog-raphy,FFDM)、DBT和MRI检查.高年资影像医师双盲阅片,参照2013版BI-RADS分类标准,以病理结果为金标准,采用受试者工作特征(operating characteristic,ROC)曲线分析各种检查方法的诊断效能,并利用Z检验比较DBT与其他检查方法的统计学差异.结果:30例患者因图像不符合诊断要求而排除,剩余197例患者共发现205个病灶,其中良性病灶73例,恶性病灶132例.B超、FFDM、DBT、DBT+FFDM和MRI基于BI-RADS分类诊断乳腺良、恶性病变的ROC曲线的曲线下面积(area under the curve,AUC)分别为0.8308、0.8592、0.9167、0.9198和0.9354;两两比较结果显示,DBT的AUC高于B超和FFDM,且差异均有统计学意义(比B超相比,Z=7.36,P=0.0067;与FFDM相比,Z=4.89,P=0.0271);DBT与MRI、DBT+FFDM的AUC差异无统计学意义(与MRI相比,Z=0.02,P=0.9002;与DBT+FFDM相比,Z=0.69,P=0.4048).结论:DBT较B超、FFDM能显著提高乳腺良、恶性病灶的诊断效能;并与MRI诊断效能相当.DBT作为乳腺X摄影新技术,具有良好的应用前景.     

Impact of full-field digital mammography on pre-operative diagnosis and surgical treatment of mammographic microcalcification

Accurate pre-operative diagnosis of impalpable breast lesions correlates closely with the number of surgical procedures required for treatment. Correct diagnosis of mammographic microcalcification (MM) as ductal carcinoma in situ (DCIS) or invasive breast cancer is important because lesions upgraded to malignant diagnosis at surgery require repeat surgical procedures in 44 % of cases. Despite correct pre-operative diagnosis of MM, 26 % require second therapeutic operations to achieve surgical clearance. Theoretically, improved conspicuity of malignant MM using digital mammography could improve diagnostic work-up and improve surgical outcomes for MM. To determine the impact of full-field digital mammography (FFDM) on the diagnostic accuracy and positive predictive value (PPV) of biopsy of MM and surgical management of MM, screening and symptomatic cases with MM (n = 1,479) were reviewed for women imaged between August 2007 and March 2010 using screen-film mammography (SFM) (n = 711), and using FFDM, imaged between April 2010 to March 2012 (n = 768). Demographic information including pre and postoperative diagnosis, and number and types of surgical procedures were recorded. Overall, 302 (128 invasive) and 251 (110 invasive) malignant lesions were diagnosed using SFM and FFDM, respectively. Reduction in PPV of biopsy was observed (SFM 42.5 %; FFDM 32.7 %, p < 0.001). Correct pre-operative diagnosis was achieved at first attempt more often with FFDM (SFM 80.6 %; FFDM 89.5 %, p < 0.001). For lesions with pre-operative diagnosis, B5 more cases achieved surgical clearance with a single therapeutic operation with FFDM (SFM 66.3 %; FFDM 76.7 %, p = 0.017), and more lesions over 2 cm underwent mastectomy as the initial surgical procedure (SFM 47.0 %; FFDM 62.9 %, p = 0.005). Correct pre-operative diagnosis of MM using digital mammography reduced second therapeutic operations but increased mastectomy rate in larger cancers over two centimetres. This will increase concerns about treatment of lesions detected in the screening programme with widespread use of digital mammography.     

Predictive and prognostic significance of cytoplasmic expression of ELAV-like protein HuR in invasive breast cancer treated with neoadjuvant chemotherapy

Cytoplasmic HuR is associated with reduced survival in invasive breast cancer. We designed this study to determine the predictive and prognostic value of HuR expression in women with breast cancer who underwent neoadjuvant chemotherapy followed by surgical resection. We immunohistochemically analyzed cytoplasmic HuR expression in tumor biopsy cores obtained from 139 patients with invasive breast cancers who received paclitaxel and anthracycline-based neoadjuvant chemotherapy. We evaluated the relationship of HuR expression level with pathologic complete response (pCR), local recurrence-free survival (LRFS), distant recurrence-free survival (DRFS), recurrence-free survival (RFS), and overall survival (OS). Cytoplasmic HuR expression was present in 60 cases (43.2 %). The expression of cytoplasmic HuR was significantly associated with high nuclear grade (P < 0.0001) and ER (P = 0.001) and PR (P = 0.005) status. Multivariate regression analysis further revealed that high nuclear grade (P = 0.023), negative ER status (P = 0.043), and human epidermal growth factor receptor 2 (HER2) overexpression (P < 0.0001), but not cytoplasmic HuR expression, were significant independent predictors of pCR. Interestingly, multivariate Cox analysis revealed that cytoplasmic HuR expression was a strong independent predictor of reduced LRFS (P = 0.014), DRFS (P = 0.001), RFS (P < 0.0001), and OS (P = 0.019) irrespective of pCR. Furthermore, the patient group with tumors showing both expression of cytoplasmic HuR and non-pCR had a worse prognosis in LRFS (P = 0.048), DRFS (P < 0.0001), RFS (P < 0.0001), and OS (P = 0.001) than did other patient groups; patients with tumors showing negative cytoplasmic expression of HuR and pCR had the best prognosis in all RFS and OS. Cytoplasmic expression of HuR is an independent prognostic marker in breast cancer patients undergoing chemotherapy. Combination analyses of HuR expression and pCR, compared with pCR alone, can better predict clinical outcome in patients with primary breast cancer.     

Diagnostic performance of breast-specific gamma imaging in the assessment of residual tumor after neoadjuvant chemotherapy in breast cancer patients

To evaluate the diagnostic performance of breast-specific gamma imaging (BSGI) in the assessment of residual tumor after neoadjuvant chemotherapy (NAC) in breast cancer patients, female breast cancer patients who underwent NAC, preoperative ^99mTc-sestamibi BSGI, and subsequent definitive breast surgery were enrolled retrospectively. The accuracy of BSGI in the assessment of residual tumor presence and residual tumor size was evaluated and compared to that of magnetic resonance imaging (MRI) using pathology results as the gold standard. The sensitivity and specificity of BSGI for residual tumor detection in 122 enrolled patients were 74.0 and 72.2 %, respectively, and were comparable to those of MRI (81.7 and 72.2 %; P > 0.100). The residual tumor size was significantly underestimated by BSGI in the luminal subtype (P = 0.008) and by MRI in the luminal (P < 0.001) and HER2 subtypes (P = 0.032), with a significantly lesser degree of underestimation by BSGI than MRI in both subtypes. In the triple-negative subtype, both BSGI and MRI generated accurate tumor size measurements. The residual cellularity of triple-negative tumors was significantly higher than that of the non-triple-negative tumors (P = 0.017). The diagnostic performance of BSGI in the assessment of residual tumor is comparable to that of MRI in breast cancer patients. The assessment of residual tumor extent by BSGI depends on the molecular subtype, but BSGI may be more accurate than MRI. Underestimation of tumor size in the luminal and/or HER2 subtypes by BSGI and MRI may be due to low-residual cellularity.     

Mammographic screening detects low-risk tumor biology breast cancers

Overdiagnosis of breast cancer, i.e. the detection of slow-growing tumors that would never have caused symptoms or death, became more prevalent with the implementation of population-based screening. Only rough estimates have been made of the proportion of patients that are overdiagnosed and identification of those patients is difficult. Therefore, the aim of this study is to evaluate whether tumor biology can help identify patients with screen-detected tumors at such a low risk of recurrence that they are likely to be overdiagnosed. Furthermore, we wish to evaluate the impact of the transition from film-screen mammography (FSM) to the more sensitive full-field digital mammography (FFDM) on the biology of the tumors detected by each screening-modality. All Dutch breast cancer patients enrolled in the MINDACT trial (EORTC-10041) accrued 2007–2011, who participated in the national screening program (biennial screening ages 50–75) were included (n = 1,165). We calculated the proportions of high-, low- and among those the ultralow-risk tumors according to the 70-gene signature for patients with screen-detected (n = 775) and interval (n = 390) cancers for FSM and FFDM. Screen-detected cancers had significantly more often a low-risk tumor biology (68 %) of which 54 % even an ultralow-risk compared to interval cancers (53 % low-, of which 45 % ultralow-risk (p = 0.001) with an OR of 2.33 (p < 0.0001; 95 % CI 1.73–3.15). FFDM detected significantly more high-risk tumors (35 %) compared to FSM (27 %) (p = 0.011). Aside from favorable clinico-pathological factors, screen-detected cancers were also more likely to have a biologically low-risk or even ultralow-risk tumor. Especially for patients with screen-detected cancers the use of tools, such as the 70-gene signature, to differentiate breast cancers by risk of recurrence may minimize overtreatment. The recent transition in screening-modalities led to an increase in the detection of biologically high-risk cancers using FFDM.     

Anthropometric factors,adult weight gain,and mammographic features

Purpose

To evaluate the association between anthropometric factors, weight gain during adulthood, and mammographic features among 1,435 women recruited at screening mammography.

Methods

Spearman’s partial coefficients were used to evaluate the correlation of anthropometric factors with mammographic features (percent density, absolute dense area, and non-dense area). Multivariate generalized linear models were used to evaluate the associations between weight change categories and mammographic features.

Results

Body mass index was inversely correlated with percent density (r = ?0.49, p < 0.0001) or absolute dense area (r = ?0.21, p < 0.0001) and positively correlated with absolute non-dense area (r = 0.69, p < 0.0001). However, body mass index was positively correlated with absolute dense area when adjusting for absolute non-dense area (r = 0.16, p < 0.0001). Similar results were observed for weight, waist circumference, and waist-to-hip ratio with mammographic features. Within increasing categories of weight change, percent density (p _trend < 0.0001) and absolute dense area (p _trend = 0.025) increased, while absolute non-dense area decreased (p _trend < 0.0001). After stratification by the median of non-dense area, the positive association between weight gain and absolute dense area remained only among women with higher non-dense area.

Conclusions

Adiposity seems positively associated with both dense and non-dense areas following adjustment for each other. Our findings suggest a higher breast dense area among women who gained weight and that a minimum of breast fat may be needed to promote the proliferation of this fibroglandular tissue.

     

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。     

Circulating estrogens and estrogens within the breast among postmenopausal BRCA1/2 mutation carriers

Accurately quantifying parent estrogens (PE) estrone (E₁) and estradiol (E₂) and their metabolites (EM) within breast tissue and serum may permit detailed investigations of their contributions to breast carcinogenesis among BRCA1/2 mutation carriers. We conducted a study of PE/EM in serum, nipple aspirate fluid (NAF), and ductal lavage supernatant (DLS) among postmenopausal BRCA1/2 mutation carriers. PE/EM (conjugated and unconjugated) were measured in paired serum/NAF (n = 22 women) and paired serum/DLS samples (n = 24 women) using quantitative liquid chromatography–tandem mass spectrometry (LC/MS/MS). The relationships between serum and tissue-specific PE/EM were measured using Pearson’s correlation coefficients. Conjugated forms of PE/EM constituted the majority of estrogen in serum (88 %), NAF (59 %) and DLS (69 %). PE/EM in NAF and serum were highly correlated [E₁ (r = 0.97, p < 0.0001), E₂ (r = 0.90, p < 0.0001) and estriol (E₃) (r = 0.74, p < 0.0001)] as they were in DLS and serum [E₁ (r = 0.92, p < 0.0001; E₂ (r = 0.70, p = 0.0001; E₃ (r = 0.67, p = 0.0004)]. Analyses of paired total estrogen values for NAF and serum, and DLS and serum yielded ratios of 0.22 (95 % CI 0.19–0.25) and 0.28 (95 % CI 0.24–0.32), respectively. This report is the first to employ LC/MS/MS to quantify PE/EM in novel breast tissue-derived biospecimens (i.e., NAF and DLS). We demonstrate that circulating PE and EM are strongly and positively correlated with tissue-specific PE and EM measured in NAF and DLS among postmenopausal BRCA1/2 mutation carriers. If confirmed, future etiologic studies could utilize the more readily obtainable serum hormone levels as a reliable surrogate measure of exposure at the tissue level.     

Genetic associations with toxicity-related discontinuation of aromatase inhibitor therapy for breast cancer

The purpose of this study was to investigate the clinical, pathological, and prognostic characteristics of breast cancer patients with diabetes. In total, the study included 1,013 breast cancer patients with diabetes and 4,621 breast cancer patients without diabetes. Patients with diabetes were further divided into the metformin- and nonmetformin-treated subgroups. The percentage of elderly patients (P < 0.001), obese patients (P < 0.001), and menopausal patients (P < 0.001) as well as the percentage of patients with cardio-cerebrovascular complications (P < 0.001), negative PR (P < 0.001) expression, or low Ki67 expression (P = 0.001) tended to be higher in the diabetic group. In addition, these patients had later pathological stages (P < 0.001), more lymph node metastasis (P = 0.014), and a lower percentage of them were on the anthracycline-based chemotherapy regimen (P = 0.003). The diabetic group was further divided into the metformin and nonmetformin-treated subgroups. The pairwise comparison between the metformin-treated subgroup and the control group did not show a significant difference in the pathological stages (P = 0.0079). However, the HER-2 positive rate tended to be lower in the metformin-treated subgroup than in the nonmetformin-treated subgroup (P = 0.002). No significant difference was found in the lymph node status between the nonmetformin-treated subgroup and the control group (P = 0.057), while the nonmetformin-treated subgroup was associated with higher HER-2 positive expression (P = 0.002). The median follow-up time for this study was 68 months (10–120 months). In Kaplan–Meier analysis, The diabetic group predicted worse survival compared with the control group (P < 0.001) with 5-year survival rates of 79 and 82 %, respectively. The breast cancer mortality rates in the metformin-treated subgroup, the nonmetformin-treated subgroup, and the control group were significantly different (long-rank test, P < 0.001), and the 5-year survival rates were 88, 73, and 82 %, respectively. As shown in the multivariate survival analysis using Cox’s regression model, compared with the control group, the metformin-treated subgroup was associated with lower mortality risk (HR 0.762; 95 % CI 0.6–0.968; P = 0.026), whereas the nonmetformin-treated subgroup was associated with higher mortality risk (HR 1.708; 95 % CI 1.461–1.997; P < 0.001). In conclusion, the diabetic group is associated with poor prognosis. Compared with the control group, the metformin-treated subgroup is associated with better clinical outcomes, while nonmetformin-treated subgroup with poorer prognosis. The selection of different antidiabetic drugs may impact the prognosis of breast cancer patients with diabetes.