Association of breast cancer with quantitative mammographic density measures for women receiving contrast-enhanced mammography.

Women with high mammographic density have an increased risk of breast cancer. They may be offered contrast-enhanced mammography to improve breast cancer screening performance. Using a cohort of women receiving contrast-enhanced mammography, we evaluated whether conventional and modified mammographic density measures were associated with breast cancer. Sixty-six patients with newly diagnosed unilateral breast cancer were frequency matched on the basis of age to 133 cancer-free control individuals. On low-energy craniocaudal contrast-enhanced mammograms (equivalent to standard mammograms), we measured quantitative mammographic density using CUMULUS software at the conventional intensity threshold ("Cumulus") and higher-than-conventional thresholds ("Altocumulus," "Cirrocumulus"). The measures were standardized to enable estimation of odds ratio per adjusted standard deviation (OPERA). In multivariable logistic regression of case-control status, only the highest-intensity measure (Cirrocumulus) was statistically significantly associated with breast cancer (OPERA = 1.40, 95% confidence interval = 1.04 to 1.89). Conventional Cumulus did not contribute to model fit. For women receiving contrast-enhanced mammography, Cirrocumulus mammographic density may better predict breast cancer than conventional quantitative mammographic density.

Contrast-Enhanced Mammography for Women with Palpable Breast Abnormalities.

RATIONALE AND OBJECTIVES: To examine the role of contrast-enhanced mammography (CEM) in the work-up of palpable breast abnormalities. MATERIALS AND METHODS: In this single-center combination prospective-retrospective study, women with palpable breast abnormalities underwent CEM evaluation prospectively, comprising the acquisition of low energy (LE) images and recombined images (RI) which depict enhancement, followed by targeted ultrasound (US). Two independent readers retrospectively reviewed the imaging and assigned BI-RADS assessment based on LE alone, LE plus US, RI with LE plus US (CEM plus US), and RI alone. Pathology results or 1-year follow-up imaging served as the reference standard. RESULTS: 237 women with 262 palpable abnormalities were included (mean age, 51 years). Of the 262 palpable abnormalities, 116/262 (44%) had no imaging correlate and 242/262 (92%) were benign. RI alone had better specificity compared to LE plus US (Reader 1, 94% versus 89% (p = 0.009); Reader 2, 93% versus 88% (p = 0.03)), better positive predictive value (Reader 1, 52% versus 42% (p = 0.04); Reader 2, 53% versus 42% (p = 0.04)), and better accuracy (Reader 1, 93% versus 89% (p = 0.05); Reader 2, 93% versus 90% (p = 0.06)). CEM plus US was not significantly different in performance metrics versus LE plus US. CONCLUSION: RI had better specificity compared to LE in combination with US. There was no difference in performance between CEM plus US and LE plus US, likely reflecting the weight US carries in radiologist decision-making. However, the results indicate that the absence of enhancement on RI in the setting of palpable lesions may help avoid benign biopsies.

Association of Breast Cancer Odds with Background Parenchymal Enhancement Quantified Using a Fully Automated Method at MRI: The IMAGINE Study.

Background Background parenchymal enhancement (BPE) at breast MRI has been associated with increased breast cancer risk in several independent studies. However, variability of subjective BPE assessments have precluded its use in clinical practice. Purpose To examine the association between fully objective measures of BPE at MRI and odds of breast cancer. Materials and Methods This prospective case-control study included patients who underwent a bilateral breast MRI examination and were receiving care at one of three centers in the United States from November 2010 to July 2017. Breast volume, fibroglandular tissue (FGT) volume, and BPE were quantified using fully automated software. Fat volume was defined as breast volume minus FGT volume. BPE extent was defined as the proportion of FGT voxels with enhancement of 20% or more. Spearman rank correlation between quantitative BPE extent and Breast Imaging Reporting and Data System (BI-RADS) BPE categories assigned by an experienced board-certified breast radiologist was estimated. With use of multivariable logistic regression, breast cancer case-control status was regressed on tertiles (low, moderate, and high) of BPE, FGT volume, and fat volume, with adjustment for covariates. Results In total, 536 case participants with breast cancer (median age, 48 years [IQR, 43-55 years]) and 940 cancer-free controls (median age, 46 years [IQR, 38-55 years]) were included. BPE extent was positively associated with BI-RADS BPE (rs = 0.54; P < .001). Compared with low BPE extent (range, 2.9%-34.2%), high BPE extent (range, 50.7%-97.3%) was associated with increased odds of breast cancer (odds ratio [OR], 1.74 [95% CI: 1.23, 2.46]; P for trend = .002) in a multivariable model also including FGT volume (OR, 1.39 [95% CI: 0.97, 1.98]) and fat volume (OR, 1.46 [95% CI: 1.04, 2.06]). The association of high BPE extent with increased odds of breast cancer was similar for premenopausal and postmenopausal women (ORs, 1.75 and 1.83, respectively; interaction P = .73). Conclusion Objectively measured BPE at breast MRI is associated with increased breast cancer odds for both premenopausal and postmenopausal women. Clinical trial registration no. NCT02301767 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Bokacheva in this issue.

Short-term follow-up of contrast-enhanced mammography lesions after negative breast MRI in women with elevated breast cancer risk.

PURPOSE: To determine the outcome of enhancing lesions detected on contrast-enhanced mammography (CEM) that had no correlate on magnetic resonance imaging (MRI) and underwent short-term follow-up CEM. METHODS: In this retrospective single-center study, we identified patients with elevated breast cancer risk who had a CEM between 2014 and 2021 showing indeterminate enhancement on recombined images (BI-RADS 0, 3, 4) that had no correlate on subsequent MRI (performed within one month), and therefore underwent short-term follow-up CEM (performed within eight months). Medical records and imaging studies were reviewed to collect data on patient and lesion characteristics, and outcomes. Cancer incidence with 95% confidence interval (CI) was calculated. RESULTS: This study included 71 women (median age 49 years) with 81 enhancing CEM lesions who underwent short-term follow-up CEM (median 6.2 months) after MRI reported no correlate. Of 81 lesions (median size = 0.7 cm), 73 (90%) were non-mass enhancement and 8 (10%) were enhancing masses. No sonographic correlate was identified for 75 lesions that had a same-day targeted ultrasound. Two cancers (2.5%, 95% CI 0.3-8.6) were diagnosed during the short-term follow-up period, one at 6-months (invasive ductal carcinoma) and one at 12-months (ductal carcinoma in situ). The remaining 79 lesions were benign at 6-month follow-up CEM and at one-year mammographic follow-up. CONCLUSIONS: Follow-up CEM of MRI-occult lesions is prudent and may be reasonable to perform at one-year given the low incidence of cancer detected at six-months (one of 81) in our small study sample.

High-Temporal/High-Spatial Resolution Breast Magnetic Resonance Imaging Improves Diagnostic Accuracy Compared With Standard Breast Magnetic Resonance Imaging in Patients With High Background Parenchymal Enhancement.

PURPOSE: To compare breast magnetic resonance imaging (MRI) diagnostic performance using a standard high-spatial resolution protocol versus a simultaneous high-temporal/high-spatial resolution (HTHS) protocol in women with high levels of background parenchymal enhancement (BPE). MATERIALS AND METHODS: We conducted a retrospective study of contrast-enhanced breast MRIs performed at our institution before and after the introduction of the HTHS protocol. We compared diagnostic performance of the HTHS and standard protocol by comparing cancer detection rate (CDR) and positive predictive value of biopsy (PPV3) among women with high BPE (ie, marked or moderate). RESULTS: Among women with high BPE, the HTHS protocol demonstrated increased CDR (23.6 per 1,000 patients v 7.9 per 1,000 patients; P = 0. 013) and increased PPV3 (16.0% v 6.3%; P = .021) compared with the standard protocol. This corresponded to a 9.8% (95% CI, 1.29 to 18.3) decrease in the proportion of unnecessary biopsies among high-BPE patients and an additional cancer yield of 15.7 per 1,000 patients (95% CI, 1.3 to 18.3). CONCLUSION: Among women with high BPE, HTHS MRI improved diagnostic performance, leading to an additional cancer yield of 15.7 cancers per 1,000 women and concomitantly decreasing unnecessary biopsies by 9.8%. A multisite prospective trial is warranted to confirm these findings and to pave the way for more widespread clinical implementation.

Contrast-enhanced mammography in the assessment of residual disease after neoadjuvant treatment.

PURPOSE: To investigate the utility of contrast-enhanced mammography (CEM) as an alternative to breast MRI for the evaluation of residual disease after neoadjuvant treatment (NAT). METHODS: This prospective study enrolled consecutive women undergoing NAT for breast cancer from July 2017-July 2019. Breast MRI and CEM exams performed after completion of NAT were read independently by two breast radiologists. Residual disease and lesion size on MRI and CEM recombined (RI) and low-energy images (LEI) were compared. Histopathology was considered the reference standard. Statistical analysis was performed using McNemar's and Leisenring's tests. Multiple comparison adjustment was made using Bonferroni procedure. Lesion sizes were correlated using Kendall's tau coefficient. RESULTS: There were 110 participants with 115 breast cancers. Residual disease (invasive cancer or ductal carcinoma in situ) was detected in 83/115 (72%) lesions on pathology, 71/115 (62%) on MRI, 55/115 (48%) on CEM RI, and 75/115 (65%) on CEM LEI. When using multiple comparison adjustment, no significant differences were detected between MRI combined with CEM LEI and CEM RI combined with CEM LEI, in terms of accuracy (MRI: 77%, CEM: 72%; p ≥ 0.99), sensitivity (MRI: 88%, CEM: 81%; p ≥ 0.99), specificity (MRI: 47%, CEM: 50%; p ≥ 0.99), PPV (MRI: 81%, CEM: 81%; p ≥ 0.99), or NPV (MRI: 60%, CEM: 50%; p ≥ 0.99). Size correlation between pathology and both MRI combined with CEM LEI and CEM RI combined with CEM LEI was moderate: τ = 0. 36 vs 0.33 (p ≥ 0.99). CONCLUSION: Contrast-enhanced mammography is an acceptable alternative to breast MRI for the detection of residual disease after neoadjuvant treatment.

MRI background parenchymal enhancement, breast density and breast cancer risk factors: A cross-sectional study in pre- and post-menopausal women.

Breast tissue enhances on contrast MRI and is called background parenchymal enhancement (BPE). Having high BPE has been associated with an increased risk of breast cancer. We examined the relationship between BPE and the amount of fibroglandular tissue on MRI (MRI-FGT) and breast cancer risk factors. This was a cross-sectional study of 415 women without breast cancer undergoing contrast-enhanced breast MRI at Memorial Sloan Kettering Cancer Center. All women completed a questionnaire assessing exposures at the time of MRI. Prevalence ratios (PR) and 95% confidence intervals (CI) describing the relationship between breast cancer risk factors and BPE and MRI-FGT were generated using modified Poisson regression. In multivariable-adjusted models a positive association between body mass index (BMI) and BPE was observed, with a 5-unit increase in BMI associated with a 14% and 44% increase in prevalence of high BPE in pre- and post-menopausal women, respectively. Conversely, a strong inverse relationship between BMI and MRI-FGT was observed in both pre- (PR = 0.66, 95% CI 0.57, 0.76) and post-menopausal (PR = 0.66, 95% CI 0.56, 0.78) women. Use of preventive medication (e.g., tamoxifen) was associated with having low BPE, while no association was observed for MRI-FGT. BPE is an imaging marker available from standard contrast-enhanced MRI, that is influenced by endogenous and exogenous hormonal exposures in both pre- and post-menopausal women.

Contrast-enhanced mammography: past, present, and future.

Contrast-enhanced mammography (CEM) combines conventional mammography with iodinated contrast material to improve cancer detection. CEM has comparable performance to breast MRI without the added cost or time of conventional MRI protocols. Thus, this technique may be useful for indications previously reserved for MRI, such as problem-solving, determining disease extent in patients with newly diagnosed cancer, monitoring response to neoadjuvant therapy, evaluating the posttreatment breast for residual or recurrent disease, and potentially screening in women at intermediate- or high-risk for breast cancer. This article will provide a comprehensive overview on the past, present, and future of CEM, including its evolving role in the diagnostic and screening settings.

Contrast-Enhanced Mammography for Screening Women after Breast Conserving Surgery.

To investigate the value of contrast-enhanced mammography (CEM) compared to full-field digital mammography (FFDM) in screening breast cancer patients after breast-conserving surgery (BCS), this Health Insurance Portability and Accountability Act-compliant, institutional review board-approved retrospective, single-institution study included 971 CEM exams in 541 asymptomatic patients treated with BCS who underwent screening CEM between January 2013 and November 2018. Histopathology, or at least a one-year follow-up, was used as the standard of reference. Twenty-one of 541 patients (3.9%) were diagnosed with ipsi- or contralateral breast cancer: six (28.6%) cancers were seen with low-energy images (equivalent to FFDM), an additional nine (42.9%) cancers were detected only on iodine (contrast-enhanced) images, and six interval cancers were identified within 365 days of a negative screening CEM. Of the 10 ipsilateral cancers detected on CEM, four were detected on low-energy images (40%). Of the five contralateral cancers detected on CEM, two were detected on low-energy images (40%). Overall, the cancer detection rate (CDR) for CEM was 15.4/1000 (15/971), and the positive predictive value (PPV3) of the biopsies performed was 42.9% (15/35). For findings seen on low-energy images, with or without contrast, the CDR was 6.2/1000 (6/971), and the PPV3 of the biopsies performed was 37.5% (6/16). In the post-BCS screening setting, CEM has a higher CDR than FFDM.

Outcome of Screening MRI in Premenopausal Women as a Function of the Week of the Menstrual Cycle.

OBJECTIVE. The objective of our study was to determine whether there are differences in outcome of screening MRI examinations in premenopausal women as a function of the week of the menstrual cycle in which the study was performed. MATERIALS AND METHODS. The reports of consecutive screening MRI examinations performed from January 1, 2011, through December 31, 2012, of premenopausal women were reviewed. Only cases for which the 1st day of the last menstrual cycle was documented were included. Associations between the week of the menstrual cycle, degree of background parenchymal enhancement (BPE), final BI-RADS assessment, positive predictive values (PPVs), cancer detection rate (CDR), sensitivity, and specificity were noted. RESULTS. A total of 1536 MRI examinations of 1239 women were performed. Distribution of MRI examinations by menstrual cycle week was as follows: 21.8% (n = 335) in week 1, 35.4% (n = 544) in week 2, 23.4% (n = 360) in week 3, and 19.3% (n = 297) in week 4. In the overall comparison, there was no significant difference in BPE, BI-RADS assessment, PPV1, PPV2, PPV3, CDR, sensitivity, or specificity by the week of the menstrual cycle. When outcomes for cases with MRI performed in week 2 were compared with those of cases with MRI performed in weeks 1, 3, and 4 combined, there was no significant difference in the same outcome measures. CONCLUSION. There was no evidence of a difference in outcomes of screening MRI examinations as a function of the week of menstrual cycle in which the study is performed. The results of our study do not support the need for screening MRI to be performed in week 2 of the menstrual cycle.

Survival Outcomes of Screening with Breast MRI in Women at Elevated Risk of Breast Cancer.

OBJECTIVE: To determine survival outcomes in women with breast cancer detected at combined screening with breast MRI and mammography versus screening mammography alone. METHODS: This is an institutional review board-approved retrospective study, and the need for informed consent was waived. A total of 3002 women with an increased risk of breast cancer were screened between 2001 and 2004. Of the 3002 women, 1534 (51.1%) had 2780 combined screenings (MRI and mammography) and 1468 (48.9%) had 4811 mammography-only screenings. The Χ 2 test and the Kaplan-Meier method were used to compare cancer detection rates and survival rates. RESULTS: The overall cancer detection rate was significantly higher in the MRI plus mammography group compared with the mammography-only group (1.4% [40 of 2780] vs 0.5% [23 of 4811]; P < 0.001). No interval cancers occurred in the MRI plus mammography group, whereas 9 interval cancers were found in the mammography-only group. During a median follow-up of 10.9 years (range: 0.7 to 15.2), a total of 11 recurrences and 5 deaths occurred. Of the 11 recurrences, 6 were in the MRI plus mammography group and 5 were in the mammography-only group. All five deaths occurred in the mammography-only group. Disease-free survival showed no statistically significant difference between the two groups (P = 0.32). However, overall survival was significantly improved in the MRI plus mammography group (P = 0.002). CONCLUSION: Combined screening with MRI and mammography in women at elevated risk of breast cancer improves cancer detection and overall survival.

Comparison of Abbreviated Breast MRI vs Digital Breast Tomosynthesis for Breast Cancer Detection Among Women With Dense Breasts Undergoing Screening.

Importance: Improved screening methods for women with dense breasts are needed because of their increased risk of breast cancer and of failed early diagnosis by screening mammography. Objective: To compare the screening performance of abbreviated breast magnetic resonance imaging (MRI) and digital breast tomosynthesis (DBT) in women with dense breasts. Design, Setting, and Participants: Cross-sectional study with longitudinal follow-up at 48 academic, community hospital, and private practice sites in the United States and Germany, conducted between December 2016 and November 2017 among average-risk women aged 40 to 75 years with heterogeneously dense or extremely dense breasts undergoing routine screening. Follow-up ascertainment of cancer diagnoses was complete through September 12, 2019. Exposures: All women underwent screening by both DBT and abbreviated breast MRI, performed in randomized order and read independently to avoid interpretation bias. Main Outcomes and Measures: The primary end point was the invasive cancer detection rate. Secondary outcomes included sensitivity, specificity, additional imaging recommendation rate, and positive predictive value (PPV) of biopsy, using invasive cancer and ductal carcinoma in situ (DCIS) to define a positive reference standard. All outcomes are reported at the participant level. Pathology of core or surgical biopsy was the reference standard for cancer detection rate and PPV; interval cancers reported until the next annual screen were included in the reference standard for sensitivity and specificity. Results: Among 1516 enrolled women, 1444 (median age, 54 [range, 40-75] years) completed both examinations and were included in the analysis. The reference standard was positive for invasive cancer with or without DCIS in 17 women and for DCIS alone in another 6. No interval cancers were observed during follow-up. Abbreviated breast MRI detected all 17 women with invasive cancer and 5 of 6 women with DCIS. Digital breast tomosynthesis detected 7 of 17 women with invasive cancer and 2 of 6 women with DCIS. The invasive cancer detection rate was 11.8 (95% CI, 7.4-18.8) per 1000 women for abbreviated breast MRI vs 4.8 (95% CI, 2.4-10.0) per 1000 women for DBT, a difference of 7 (95% CI, 2.2-11.6) per 1000 women (exact McNemar P = .002). For detection of invasive cancer and DCIS, sensitivity was 95.7% (95% CI, 79.0%-99.2%) with abbreviated breast MRI vs 39.1% (95% CI, 22.2%-59.2%) with DBT (P = .001) and specificity was 86.7% (95% CI, 84.8%-88.4%) vs 97.4% (95% CI, 96.5%-98.1%), respectively (P < .001). The additional imaging recommendation rate was 7.5% (95% CI, 6.2%-9.0%) with abbreviated breast MRI vs 10.1% (95% CI, 8.7%-11.8%) with DBT (P = .02) and the PPV was 19.6% (95% CI, 13.2%-28.2%) vs 31.0% (95% CI, 17.0%-49.7%), respectively (P = .15). Conclusions and Relevance: Among women with dense breasts undergoing screening, abbreviated breast MRI, compared with DBT, was associated with a significantly higher rate of invasive breast cancer detection. Further research is needed to better understand the relationship between screening methods and clinical outcome. Trial Registration: ClinicalTrials.gov Identifier: NCT02933489.

Performance of Dual-Energy Contrast-enhanced Digital Mammography for Screening Women at Increased Risk of Breast Cancer.

BackgroundContrast agent-enhanced digital mammography (CEDM) has been shown to be more sensitive and specific than two-dimensional full-field digital mammography in the diagnostic setting. Few studies have reported on its performance in the screening setting.PurposeTo evaluate the performance of CEDM for breast cancer screening.Materials and MethodsThis retrospective study included women who underwent dual-energy CEDM for breast cancer screening from December 2012 through April 2016. Medical records were reviewed for age, risk factors, short-interval follow-up and biopsies recommended, and cancers detected. Sensitivity, specificity, positive predictive value of abnormal findings at screening (PPV1), positive predictive value of biopsy performed (PPV3), and negative predictive value were determined.ResultsIn the study period 904 baseline CEDMs were performed. Mean age was 51.8 years ± 9.4 (standard deviation). Of 904 patients, 700 (77.4%) had dense breasts, 247 (27.3%) had a family history of breast cancer in a first-degree relative age 50 years or younger, and 363 (40.2%) a personal history of breast cancer. The final Breast Imaging Reporting and Data System score was 1 or 2 in 832 of 904 (92.0%) patients, score of 3 in 25 of 904 (2.8%) patients, and score of 4 or 5 in 47 of 904 (5.2%) patients. By using CEDM, 15 cancers were diagnosed in 14 of 904 women (cancer detection rate, 15.5 of 1000). PPV3 was 29.4% (15 of 51). At least 1-year follow up was available in 858 women. There were two interval cancers. Sensitivity was 50.0% (eight of 16; 95% confidence interval [CI]: 24.7%, 75.3%) on the low-energy images compared with 87.5% (14 of 16; 95% CI: 61.7%, 98.4%) for the entire study (low-energy and iodine images; P = .03). Specificity was 93.7% (789 of 842; 95% CI: 91.8%, 95.2%); PPV1 was 20.9% (14 of 67; 95% CI: 11.9%, 32.6%), and negative predictive value was 99.7% (789 of 791; 95% CI: 99.09%, 99.97%).ConclusionContrast-enhanced digital mammography is a promising technique for screening women with higher-than-average risk for breast cancer.© RSNA, 2019.

Preoperative breast MRI features associated with positive or close margins in breast-conserving surgery.

PURPOSE: To determine preoperative magnetic resonance imaging (MRI) features associated with positive or close margins in patients with breast cancer who underwent breast-conserving surgery (BCS). MATERIALS AND METHODS: A retrospective review identified 249 patients with invasive ductal carcinoma (IDC) who underwent preoperative MRI and BCS as a primary procedure between 2008 and 2010. The MR images were reviewed for descriptions of findings with no new interpretations made. Margins were defined as positive (tumor touching the inked specimen margin), close (<2 mm tumor-free margin), or negative (≥2 mm tumor-free margin). Multivariate logistic regression analysis was performed to evaluate imaging and clinical factors predictive of positive or close margins. RESULTS: Of the 249 patients, 83 (33.3%) had positive or close margins and 166 (66.7%) had negative margins on the initial BCS specimen. Multivariate analysis showed that multifocal disease (odds ratio, 4.8; 95% CI, 1.9-12.2; p =  0.001), nonmass enhancement lesion (odds ratio, 3.0; 95% CI, 1.5-6.2, p =  0.003), greater background parenchymal enhancement (odds ratio, 2.5; 95% CI, 1.1-5.6; p =  0.023), larger lesion size (odds ratio, 1.3; 95% CI, 1.0-1.7, p =  0.032), and presence of ductal carcinoma in situ on needle biopsy (odds ratio, 2.4; 95% CI, 1.3-4.6; p = 0.008) were independent predictors of positive or close margins. CONCLUSIONS: Multifocal disease, nonmass enhancement lesion, or greater background parenchymal enhancement on preoperative breast MRI were significantly associated with positive or close margins. Identifying these MRI features before surgery can be helpful to reduce the reoperation rate in BCS.

Automated Breast Density Measurements From Chest Computed Tomography Scans.

To develop an automated method for quantifying percent breast density from chest computed tomography (CT) scans. A naïve Bayesian classifier based on gray-level intensities and spatial relationships was developed on CT scans from 10 patients diagnosed with Hodgkin lymphoma (HL) and imaged as part of routine clinical care. The algorithm was validated on CT scans from 75 additional HL patients. The classifier was developed and validated using a reference dataset with consensus manual segmentation of fibroglandular tissue. Accuracy was evaluated at the pixel-level to examine how well the algorithm identified pixels with fibroglandular tissue using true and false positive fractions (TPF and FPF, respectively). Quantitative estimates of the patient-level CT percent density were contrasted to each other using the concordance correlation coefficient, ρc, and to subjective ACR BI-RADS density assessments using Kendall's τb. The pixel-level TPF for identifying pixels with fibroglandular tissue was 82.7% (interquartile range of patient-specific TPFs 65.5%-89.6%). The pixel-level FPF was 9.2% (interquartile range of patient-specific FPFs 2.5%-45.3%). Patient-level agreement of the algorithm's automated density estimate with that obtained from the reference dataset was high, ρc = 0.93 (95% CI 0.90-0.96) as was agreement with a radiologist's subjective ACR-BI-RADS assessments, τb = 0.77. It is possible to obtain automated measurements of percent density from clinical CT scans.

Differences in degree of lesion enhancement on CEM between ILC and IDC.

OBJECTIVE: To investigate differences in the degree of enhancement on contrast-enhanced mammography (CEM) between patients with invasive lobular (ILC) and infiltrating ductal carcinoma (IDC) not otherwise specified. METHODS AND MATERIALS: Between 2010 and 2017, all patients diagnosed with ILC and who underwent CEM were included for this dual center study. Twenty-two patients with IDC, matched by size, were identified for comparison. Three independent readers, blinded for histopathology results, re-evaluated all CEM exams to determine degree of lesion enhancement according to a previously defined scoring scale ranging from minimal to strong enhancement. Interobserver agreement among the three readers was calculated by quadratic weighted κ coefficient. RESULTS: 44 patients were included: 22 patients with ILC and 22 patients with IDC. There were no significant differences in age, mean tumor size, tumor grade or receptor status between the two subgroups. Degree of lesion enhancement on CEM was more often considered weak in case of ILC compared to IDC according to two out of three readers (31.8% vs 4.5 %, p = 0.045 and 22.7 vs 4.5 %, p = 0.185). All other lesions showed moderate or strong enhancement. Interobserver agreement between the three independent readers was good (κ = 0.72). CONCLUSION: In patients with ILC, degree of lesion enhancement on CEM appears to be more often weak than in infiltrating ductal carcinoma not otherwise specified. Radiologists should be aware that weakly enhancing lesions may in fact be malignant and particularly invasive lobular cancers. ADVANCES IN KNOWLEDGE: Three independent readers evaluated 44 CEM cases with ILC or IDC. Degree of lesion enhancement seems more often weak in case of ILC. Radiologists should be aware of ILC in case of weak CEM enhancement.

Histopathologic characteristics of background parenchymal enhancement (BPE) on breast MRI.

PURPOSE: Breast fibroglandular tissue (FGT), as visualized on a mammogram (mammographic density, MD), is one of the strongest known risk factors for breast cancer. FGT is also visible on breast MRI, and increased background parenchymal enhancement (BPE) in the FGT has been identified as potentially a major breast cancer risk factor. The aim of this exploratory study was to examine the biologic basis of BPE. METHODS: We examined the unaffected contra-lateral breast of 80 breast cancer patients undergoing a prophylactic mastectomy before any treatment other than surgery of their breast cancer. BPE was classified on the BI-RADS scale (minimal/mild/moderate/marked). Slides were stained for microvessel density (MVD), CD34 (another measure of endothelial density), glandular tissue within the FGT and VEGF. Spearman correlations were used to evaluate the associations between BPE and these pathologic variables. RESULTS: In pre-menopausal patients, BPE was highly correlated with MVD, CD34 and glandular concentration within the FGT, and the pathologic variables were themselves highly correlated. The expression of VEGF was effectively confined to terminal duct lobular unit (TDLU) epithelium. The same relationships of the four pathologic variables with BPE were seen in post-menopausal patients, but the relationships were much weaker and not statistically significant. CONCLUSION: The strong correlation of BPE and MVD together with the high correlation of MVD with glandular concentration seen in pre-menopausal patients indicates that increased breast cancer risk associated with BPE in pre-menopausal women is likely to result from its association with increased concentration of glandular tissue in the FGT. The effective confinement of VEGF expression to the TDLUs shows that the signal for MVD growth arises directly from the glandular tissue. Further studies are needed to understand the basis of BPE in post-menopausal women.

MRI background parenchymal enhancement, breast density and serum hormones in postmenopausal women.

Background parenchymal enhancement (BPE) is the degree to which normal breast tissue enhances on contrast-enhanced magnetic resonance imaging (MRI). MRI-density is a volumetric measure of breast density that is highly correlated with mammographic density, an established breast cancer risk factor. Endogenous estrogen concentrations are positively associated with postmenopausal breast cancer risk and BPE has been shown to be sensitive to hormonal exposures. The objective of our study was to examine the relationship between BPE and MRI-density and serum hormone concentrations in postmenopausal women. This was a study of cancer-free postmenopausal women undergoing contrast-enhanced breast MRI (N = 118). At the time of MRI all women completed a self-administered questionnaire and blood samples were collected for hormone analyses. Serum concentrations of estrone (E1), estradiol (E2) and bioavailable E2 were examined by category of BPE and MRI-density. Compared to women with "minimal" BPE, those who had "marked" BPE had significantly higher serum concentrations of E1, E2 and bioavailable E2 (90% increase, ptrend across all categories = 0.001; 150% increase, ptrend = 0.001; and 158% increase, ptrend = 0.001, respectively). These associations were only affected to a minor extent by adjustment for BMI and other variables. After adjustment for BMI, no significant associations between MRI-density and serum E1, E2 and bioavailable E2 were observed. Serum estrogen concentrations were significantly positively associated with BPE. Our study provides further evidence of the hormone-sensitive nature of BPE, indicating a potential role for BPE as an imaging marker of endogenous and exogenous hormonal exposures in the breast.

Comparison of screening CEDM and MRI for women at increased risk for breast cancer: A pilot study.

OBJECTIVES: Contrast enhanced digital mammography (CEDM) is a new breast imaging technology increasingly used in the diagnostic setting but its utility in the pure screening setting has not been reported. The goal of this pilot study is to prospectively compare screening CEDM to breast MRI in women with an increased risk for breast cancer. METHODS: In this IRB-approved HIPAA-compliant study, 318 women at increased breast cancer risk were consented (December 2012-May 2015) to undergo CEDM in addition to their scheduled MRI. CEDM was performed within 30days of screening MRI. CEDM was interpreted blinded to MRI. The reference standard was defined as a combination of pathology and 2-year imaging follow-up. RESULTS: Data from 307/318 patients were evaluable. Three cancers (two invasive cancers, one ductal carcinoma in situ) were detected at first round screening: MRI detected all three and CEDM detected the two invasive cancers. None of the three cancers was seen on the low energy mammograms which are comparable to conventional mammography. At 2year imaging follow up, there were 5 additional screen detected cancers and no palpable cancers. The positive predictive value 3 (PPV3) for CEDM was 15% (2/13, 95% CI: 2-45%) and 14% for MRI (3/21, 95% CI: 3-36%). The specificity of CEDM and MRI were 94.7% and 94.1% respectively. CONCLUSIONS: Both CEDM and MRI detected additional cancers not seen on conventional mammography, primarily invasive cancers. Our pilot data suggest that CEDM could be valuable as a supplemental imaging exam for women at increased risk for breast cancer who do not meet the criteria for MRI or for whom access to MRI is limited. Validation in larger multi institutional trials is warranted.