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. 2025 Mar 11;314(3):e242006. doi: 10.1148/radiol.242006

Comparison of Contrast-enhanced Mammography and Low-Energy Imaging with or without Supplemental Whole-Breast US in Breast Cancer Detection

Joao V Horvat 1, Tali Amir 1, Gordon P Watt 1, Christopher E Comstock 1, Noam Nissan 1, Maxine S Jochelson 1, Janice S Sung 1,✉
Editor: Linda Moy
PMCID: PMC11950873  PMID: 40067106

Abstract

Background

Contrast-enhanced mammography (CEM) is an emerging modality that generates low-energy (LE) images that are visually equivalent to full-field digital mammography (FFDM) and recombined images that show lesion vascularity such as MRI. Supplemental whole-breast US increases cancer detection rates when performed with FFDM but not with MRI.

Purpose

To compare the performance of CEM, LE images, and LE images supplemented with whole-breast US in breast cancer detection during screening.

Materials and Methods

This prospective study recruited female participants from December 2014 to February 2019 who were scheduled for screening mammography and whole-breast US. CEM (including LE images and recombined images) and whole-breast US images were interpreted by separate breast radiologists blinded to the findings on images from the other modality. Statistical differences in sensitivity and specificity, positive predictive value (PPV), negative predictive value, and abnormal interpretation rate were assessed. Biopsy recommendation rate and PPVs of biopsies performed (PPV3) were calculated at the lesion level.

Results

Across 468 participants (median age, 54 years [IQR, 48–59 years]; all female participants), nine screen-detected cancers were diagnosed in eight participants: one cancer was depicted at LE imaging alone (cancer detection rate, 2.1 of 1000), four were depicted at LE imaging with whole-breast US (cancer detection rate, 8.5 of 1000), and eight were depicted at CEM (cancer detection rate, 17.1 of 1000; P < .05). The abnormal interpretation rate was 10.3% (48 of 468) for LE images, 13.7% (64 of 468) for LE images with whole-breast US, and 18.6% (87 of 468) for CEM (P < .001). The biopsy recommendation rate was 15.0 of 1000 for LE images, 38.4 of 1000 for LE images with whole-breast US, and 42.7 of 1000 for CEM. Seven biopsies were recommended based on LE images (PPV3 of one of seven [14.3%]), 18 biopsies based on LE images with whole-breast US (with a PPV3 of five of 18 [27.8%]), and 20 biopsies based on CEM (PPV3 of 9 of 20 [45.0%]).

Conclusion

Breast cancer detection improved with CEM compared with LE images alone or LE images with whole-breast US.

ClinicalTrials.gov Identifier: NCT02310698

© RSNA, 2025

Supplemental material is available for this article.

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Summary

Breast cancer detection improved with contrast-enhanced mammography compared with low-energy imaging alone or low-energy imaging with whole-breast US.

Key Results

  • ■ In this prospective study of 468 women who underwent screening for breast cancer, the cancer detection rate was highest for contrast-enhanced mammography (CEM; 17.1 of 1000) compared with low-energy (LE) images alone (2.1 of 1000) or LE images with supplemental whole-breast US (8.5 of 1000; overall P < .05).

  • ■ CEM was associated with a higher abnormal interpretation rate (18.6% [87 of 468] vs 10.3% [48 of 468] for LE images and 13.7% [64 of 468] for LE images with supplemental whole-breast US) and an increased number of biopsies (42.7 of 1000 for CEM vs 15.0 of 1000 for LE images, and 38.4 of 1000 for LE images with whole-breast US) compared with LE images or LE images with supplemental whole-breast US.

Introduction

Breast cancer is the most common type of cancer in women and the second most common cause of cancer-related death in women in the United States (1). Although mammography can depict a large percentage of cancers, sensitivity is limited in women with dense breasts (2,3).

Supplementing screening mammography with US increases the cancer detection rate, especially in women with dense breasts (4). However, the increased sensitivity is associated with increased rates of false-positive findings (4). Breast MRI has been consistently demonstrated to reduce the interval cancer rate (5) and has a higher cancer detection rate compared with full-field digital mammography (FFDM) alone or FFDM supplemented with whole-breast US (6–8). However, because of limited access, moderate specificity, and high cost (9,10), annual screening MRI is reserved for patients with an increased lifetime risk of breast cancer of at least 20% (11).

Contrast-enhanced mammography (CEM) is an emerging modality that generates low-energy (LE) images that are visually equivalent to two-dimensional FFDM (12) and recombined images that also show lesion vascularity similar to MRI (13). Studies have reported comparable performance between CEM and MRI (14,15), with the advantage of reduced cost with CEM compared with breast MRI (9). CEM has increasingly been used for screening, especially in women at increased risk of breast cancer (16–18). Studies have shown that whole-breast US does not help increase cancer detection with screening MRI. This may also be true for CEM (19).

This study hypothesized that, similar to breast MRI, whole-breast US does not help increase cancer detection following screening CEM. This study investigated the performance of LE images, LE images supplemented with whole-breast US, and CEM in detecting cancer at breast cancer screening.

Materials and Methods

Participants

In this institutional review board–approved, prospective, single-center study at Memorial Sloan Kettering Cancer Center (New York, NY), consecutive women scheduled for routine annual screening CEM or mammography and whole-breast US (within 30 days of one another) between December 2014 and February 2019 were recruited. This study was compliant with the Health Insurance Portability and Accountability Act and is registered at ClinicalTrials.gov (NCT02310698). Informed consent was obtained from all participants. Inclusion criteria were asymptomatic female participants aged 30 years or older who were due for their annual mammography examination and scheduled for supplemental whole-breast US. Exclusion criteria included clinical breast cancer symptoms, breast cancer diagnosis or treatment within the previous 3 years, breast surgery or biopsy within previous 90 days, breast MRI within previous 3 years, breast implants, known allergy or contraindication to iodinated contrast media, and pregnant or lactating women. Figure 1 shows the participant flow diagram.

Figure 1:

Flow diagram of participant accrual. Lesions seen only on contrast-enhanced mammographic recombined images were recommended for breast MRI.

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Flow diagram of participant accrual. Lesions seen only on contrast-enhanced mammographic recombined images were recommended for breast MRI.

Participants in this study overlapped with six previously published retrospective studies (Appendix S1).

Race and ethnicity categories were self-selected by participants on an intake form at their initial registration at Memorial Sloan Kettering Cancer Center and subsequently recorded from the electronic medical record. Personal and family histories were recorded from the electronic medical record.

Imaging Protocol

Participants underwent CEM followed by whole-breast US during the same visit. Details regarding the imaging protocol are provided in Appendix S1.

Imaging Analysis

For each participant, one of 18 breast radiologists (with 1–30 years of experience in breast imaging) at Memorial Sloan Kettering Cancer Center interpreted the CEM and recorded their findings on a data form. A second breast radiologist, also one of the same 18 breast radiologists, who was blinded to the findings at CEM interpreted the whole-breast US. At Memorial Sloan Kettering Cancer Center, two to three radiologists were on service each day, interpreting CEM images, mammograms, and US images with same-day reads. The images obtained with CEM, mammography, and US were distributed randomly to each interpreting radiologist. CEM LE images were considered equivalent to FFDM images and were interpreted before viewing the recombined images. Data forms were completed at the time of interpretation to determine whether an abnormality was depicted on the LE images, recombined images, or both. For LE and CEM images, the abnormal interpretation rate included participants with a recommendation for additional mammographic views, US, or MRI. For whole-breast US, the abnormal interpretation rate included any study in which the radiologist scanned to further characterize an abnormality detected by the technologist. Once indeterminate findings for each modality were recorded, the participant was managed per standard institutional practice after integrating findings of both CEM and whole-breast US.

Lesion Management

Additional views at mammography and targeted breast US were performed in all participants with indeterminate findings at either screening CEM or whole-breast US at the discretion of the radiologist reading the CEM image. A final assessment, including Breast Imaging Reporting and Data System (or BI-RADS) categorization, was issued after the necessary additional imaging evaluation was performed. Lesions found at sonography that were deemed suspicious for cancer were recommended for US-guided biopsy. Lesions that were suspicious for cancer and observed only on CEM images were recommended for stereotactic-guided biopsy if the lesion could be identified on LE images. Lesions observed only on CEM recombined images were recommended for breast MRI. If a suspicious correlate was identified at MRI, MRI-guided biopsy was recommended, whereas participants with negative findings at MRI were recommended for a 6-month follow-up ipsilateral CEM. An illustration of lesion management is shown in Figure 2.

Figure 2:

Flow diagram shows lesion management after integration of findings on images from screening contrast-enhanced mammography (CEM) and whole-breast US. All participants underwent CEM followed by whole-breast US during the same visit. Lesions seen only on CEM recombined images were recommended for breast MRI. If a suspicious correlate was identified at MRI, MRI-guided biopsy was recommended, whereas participants with a result negative for cancer at MRI were recommended for a 6-month follow-up (FU) ipsilateral CEM.

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Flow diagram shows lesion management after integration of findings on images from screening contrast-enhanced mammography (CEM) and whole-breast US. All participants underwent CEM followed by whole-breast US during the same visit. Lesions seen only on CEM recombined images were recommended for breast MRI. If a suspicious correlate was identified at MRI, MRI-guided biopsy was recommended, whereas participants with a result negative for cancer at MRI were recommended for a 6-month follow-up (FU) ipsilateral CEM.

All participants were followed for 1 year or until the next screening mammography if performed 300–365 days after the initial CEM and whole-breast US. All breast cancers detected during the follow-up period were documented. Interval cancer was defined as a breast cancer detected within 365 days of the negative result at CEM and whole-breast US, before the next screening mammographic examination.

Statistical Analysis

Descriptive statistics were summarized using medians, ranges, and proportions. Invasive breast carcinomas and ductal carcinomas in situ were combined and referred to as cancers for statistical analysis. CEM LE images served as surrogates for FFDM, whereas the combination of CEM recombined images and CEM LE images was referred to as CEM. Cancer detection rate of participants per 1000 examinations was calculated for LE images, LE images with whole-breast US, and CEM. Differences in cancer detection rates were tested using Cochrane Q test. The sensitivity, specificity, positive predictive value (PPV), negative predictive value, and abnormal interpretation rate for each screening protocol were calculated and compared at the participant level. Comparisons between sensitivity and specificity were made using the exact binomial test (20), and comparisons between PPV and negative predictive value were made using the relative predictive value approach as described by Moskowitz and Pepe (21). The biopsy recommendation rate and PPVs of biopsies performed (PPV3) were calculated at the lesion level. All tests were two-sided, and P < .05 was considered to indicate statistical significance. Statistical software (R, version 4.1.2; R Foundation for Statistical Computing) was used for all analyses (G.P.W., with 10 years of experience). A minimal study sample was not established because prediction of differences in sensitivity could not be determined when the study protocol was conceived. A maximum of 1500 participants was established due to logistical and financial considerations.

Results

Participant Characteristics

A total of 486 female participants was recruited. Of these, 18 (3.7%) were excluded from the study, including 11 who opted to withdraw after providing consent, four who underwent a diagnostic study for a clinical symptom, one who underwent mammography recently, one with a history of allergy to iodinated soap, and one participant in whom intravenous access for contrast injection could not be obtained. The final study sample was composed of 468 participants. The median age of participants was 54 years (IQR, 48–59 years; age range, 30–78 years). Regarding race and ethnicity, according to self-selected categories, 25 participants (5.3%) were Hispanic, 36 (7.7%) were non-Hispanic Asian, 24 (5.1%) were non-Hispanic Black, eight (1.7%) were non-Hispanic “other,” and 75 (80.1%) were White. Of the 468 participants, 450 (96.2%) had an intermediate or high risk of breast cancer: 292 (62.4%) had a personal history of breast cancer; 246 (52.6%) had a family history of breast cancer, including 168 (35.9%) with a history of breast cancer in a first-degree relative; 119 (25.4%) had a history of high-risk lesion or lesions; four (0.8%) had a history of mantle radiation; and one (0.2%) carried the BRCA1 mutation. The remaining 18 participants (3.8%) had an average lifetime risk of breast cancer. A considerable majority of participants, 406 (86.8%), had mammographically dense breasts, whereas 62 (13.2%) had nondense breasts. All but 22 participants (4.7%) underwent follow-up imaging at 300 days or longer after the initial CEM and whole-breast US examinations. Participant characteristics are provided in Table 1.

Table 1:

Characteristics of Study Sample

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Cancer Detection

Ten cancers were detected in nine of 468 participants (cancer detection rate, 19 of 1000) in the study sample, including nine screen-detected cancers and one interval cancer diagnosed at MRI 6 months after the participant underwent research CEM and whole-breast US. Of these cancers, six were invasive and four were ductal carcinomas in situ. The diagnosed breast cancers are listed in Table 2. Nine cancers were detected in eight women with dense breasts; five of these were visible on whole-breast US images. One cancer (ductal carcinoma in situ) was depicted on LE images, five cancers (three invasive carcinomas and two ductal carcinomas in situ) in four women were depicted on LE images with whole-breast US, and nine cancers (six invasive carcinomas and three ductal carcinomas in situ) in eight women were depicted on CEM images. All screen-detected cancers were observed on CEM images. Figures 3 and 4 show examples of true-positive and false-positive findings on CEM images, respectively. One interval cancer was diagnosed at MRI 6 months after the research CEM and whole-breast US, with pathologic analysis confirming ductal carcinoma in situ. The cancer detection rate was 2.1 of 1000 for LE images alone, 8.5 of 1000 for LE images with whole-breast US, and 17.1 of 1000 for CEM (P = .02). Sensitivity was 11% (one of nine; 95% CI: 0.3, 48) for LE images, 44% (four of nine) for LE images with whole-breast US (95% CI: 14, 79), and 89% (eight of nine) for CEM (95% CI: 52, 100). The differences in sensitivities were 78% greater (95% CI: 50, 100) for CEM versus LE images, 33% greater (95% CI: 2.5, 64) for whole-breast US versus LE images, and 44% greater (95% CI: 12, 77) for CEM versus whole-breast US. Specificity was 96.9% (445 of 459) for LE images, 93.9% (431 of 459) for LE images with whole-breast US, and 90.2% (414 of 459) for CEM. The differences in specificities were 6.8% less (95% CI: −9.1, −4.5) for CEM versus LE images, 3.1% less (95% CI: −4.6, −1.5) for whole-breast US versus LE images; and 3.7% less (95% CI: −6.1, −1.3) for CEM versus whole-breast US. A comparison of the performances of CEM, LE images alone, and LE images with whole-breast US is given in Table 3.

Table 2:

Characteristics of Study Participants Diagnosed with Breast Cancer

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Figure 3:

True-positive findings in a 51-year-old woman with a left breast focal nonmass enhancement. (A) Mediolateral oblique and (B) craniocaudal contrast-enhanced mammographic (CEM) images show the enhancement (arrows). No correlate was identified on (C) mediolateral-oblique or (D) craniocaudal low-energy images, or whole-breast US (not shown). Contrast-enhanced breast MRI shows a suspicious enhancement on (E) sagittal and (F) axial subtraction images (arrows), correlating with the finding on CEM images. MRI-guided biopsy (not shown) showed flat epithelial atypia, with subsequent surgery confirming ductal carcinoma in situ.

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True-positive findings in a 51-year-old woman with a left breast focal nonmass enhancement. (A) Mediolateral oblique and (B) craniocaudal contrast-enhanced mammographic (CEM) images show the enhancement (arrows). No correlate was identified on (C) mediolateral-oblique or (D) craniocaudal low-energy images, or whole-breast US (not shown). Contrast-enhanced breast MRI shows a suspicious enhancement on (E) sagittal and (F) axial subtraction images (arrows), correlating with the finding on CEM images. MRI-guided biopsy (not shown) showed flat epithelial atypia, with subsequent surgery confirming ductal carcinoma in situ.

Figure 4:

False-positive finding in a 74-year-old woman with a history of left-breast excision for lobular carcinoma in situ with focal nonmass enhancement. (A) Mediolateral oblique and (B) cranial caudal contrast-enhanced mammographic images along the anterior aspect of the surgical bed show the enhancement (arrows). Contrast-enhanced breast MRI shows suspicious enhancement on (C) sagittal and (D) axial subtraction images (arrows). MRI-guided biopsy (not shown) yielded dense stromal fibrosis and findings consistent with the prior procedure.

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False-positive finding in a 74-year-old woman with a history of left-breast excision for lobular carcinoma in situ with focal nonmass enhancement. (A) Mediolateral oblique and (B) cranial caudal contrast-enhanced mammographic images along the anterior aspect of the surgical bed show the enhancement (arrows). Contrast-enhanced breast MRI shows suspicious enhancement on (C) sagittal and (D) axial subtraction images (arrows). MRI-guided biopsy (not shown) yielded dense stromal fibrosis and findings consistent with the prior procedure.

Table 3:

Performance Measures for Low-Energy Images, Contrast-enhanced Mammography, and Whole-Breast US in Detecting Invasive Breast Cancer or Ductal Carcinoma in Situ

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Abnormal Interpretation Rate

The abnormal interpretation rate was 10.3% (48 of 468) for LE images, 13.7% (64 of 468) for LE images with whole-breast US, and 18.6% (87 of 468) for CEM (overall P < .001). Breast MRI was recommended for further characterization of an area of enhancement on the recombined images only in 6.20% (29 of 468) of participants.

Biopsies Recommended and Performed

A total of 29 biopsies were recommended and performed in 28 participants: six biopsies were performed with stereotactic guidance, 15 with US guidance, and eight with MRI guidance. The biopsy recommendation rate was 15.0 of 1000 for LE images, 38.4 of 1000 for LE images with whole-breast US, and 42.7 of 1000 for CEM. Seven biopsies were recommended for LE images with a PPV3 of one of seven (14%), 18 biopsies for LE images with whole-breast US with a PPV3 of five of 18 (28%), and 20 biopsies for findings on CEM images with a PPV3 of nine of 20 (45%).

Short-term Follow-up and Adverse Events

Short-term follow-up (BI-RADS category 3) and adverse event results are given in Appendix S1.

Discussion

Whole-breast US is known to help increase the cancer detection rate compared with full-field digital mammography (FFDM) (4) but not in women who have undergone screening MRI. Contrast-enhanced mammography (CEM) is a vascular-based imaging test similar to MRI and yields both low-energy (LE) images (that are equivalent to images generated with FFDM) and recombined images. This prospective study compared the performances of LE images, LE images with whole-breast US, and CEM in breast cancer screening. In the study sample of predominantly intermediate- and high-risk women, CEM sensitivity was higher than that of LE images (89% [eight of nine] vs 11% [one of nine]; P < .02) and the addition of supplemental whole-breast US to CEM did not improve the cancer detection rate (LE images, 2.1 of 1000; LE image with whole-breast US, 8.5 of 1000; CEM, 17.1 of 1000). All screen-detected cancers were seen on CEM images, and the combination of LE images with whole-breast US missed five cancers (four invasive and one ductal carcinoma in situ) in four participants that were depicted on CEM images.

Our findings support published retrospective studies on the performance of CEM in patients at elevated risk of breast cancer and the role of supplemental whole breast US. Sung et al (17) reported a cancer detection rate of 15.5 per 1000 for CEM in women with an elevated risk of breast cancer, similar to our cancer detection rate of 17.1 per 1000. Sorin et al (16) reported that the sensitivity of CEM exceeded that of mammography, 91% versus 52%, compared with 89% versus 11% in our study. Similar to our results, they also reported that no additional cancers were detected at US in women undergoing CEM. Klang et al (19) also concluded that US findings with negative findings at CEM contributed to false-positive biopsy results.

Vascular-based imaging techniques, including CEM and MRI, have demonstrated higher sensitivity than FFDM (17,22–26). The neovascularity of malignant tumors results in increased enhancement after contrast agent administration (13). Increased breast density, which reduces sensitivity of FFDM (3,27), does not affect cancer detection with vascular imaging. Unlike mammography or US, vascular-based imaging techniques do not necessarily require morphologic changes such as masses, calcifications, or architectural distortion to develop before a cancer can be detected.

More cancers were detected with supplemental whole-breast US than with LE images alone, which agrees with previous studies that showed the added value of screening whole-breast US, especially for participants with mammographically dense breasts (8,28–30). However, the cancers identified on whole-breast US images in our study were also detected on CEM images, suggesting that whole-breast US does not improve cancer detection in participants undergoing screening CEM.

The increased sensitivity of CEM was associated with lower specificity; more women required additional imaging and more short-term follow-ups, and more biopsies were recommended because of findings seen on CEM images compared with LE images alone or LE images with whole-breast US. The abnormal interpretation rate (ie, the number of women recommended for additional imaging) for CEM was 18.6%, which is higher than the established benchmark of 5%–12% for mammography (3,31). CEM was also associated with an increased number of biopsies recommended and performed. However, the PPV3 of CEM was 45% (nine of 20), which was greater than the PPV3 of LE images and LE images with whole-breast US. Therefore, the increased number of cancers detected may compensate for the additional imaging and biopsies.

Screening CEM led to the recommendation and performance of breast MRI in 6.2% (29 of 468) of participants. CEM-guided biopsy was not available at our institution during the study period; therefore, participants with indeterminate findings seen only on CEM recombined images were recommended to undergo breast MRI. The feasibility of CEM-guided biopsy has been recently demonstrated in the literature (32,33), and an increasing number of medical centers, including ours (ie, Memorial Sloan Kettering Cancer Center), are adopting this novel biopsy modality. The adoption of CEM-guided biopsy will make most of these additional diagnostic MRI examinations unnecessary in a screening CEM setting. The rates of short-term follow-up were similar for CEM, LE images, and LE images with whole-breast US (3.6% [17 of 468] vs 1.7% [eight of 468] vs 3.4% [16 of 468], respectively). In a previous publication by Berg et al (34) with more than 7 million screening mammograms, a BI-RADS category 3 rate of approximately 2% was reported, similar to our findings with LE images. Although performing supplemental screening with CEM or whole-breast US resulted in additional recommendations for a short-term follow-up, the overall BI-RADS category 3 rates remained low.

As noted, no severe reaction to iodine-based contrast media was observed in the study sample, but mild adverse events were observed in 0.8% (four of 468) of participants. Previous publications (35–37) about CEM also reported no severe reactions to contrast media. Severe adverse reactions to contrast media are rare (38) but can occur during a CEM examination. Measures to mitigate these events include not performing CEM in patients with a history of allergic reaction to iodine-based contrast media.

Our study had limitations. First, breast cancer risk assessment was not performed prior to study enrollment, and participants with different lifetime risks for developing breast cancer were included. Second, the target accrual was not achieved during the study period. This may be due to several reasons: patient hesitancy to undergo CEM at a time when CEM was not well known, concerns around intravenous contrast agent, and the longer appointment time for screening for contraindications and for placing an intravenous catheter. Third, CEM-guided biopsy was not available during the enrollment period; therefore, participants with an indeterminate finding seen only on CEM recombined images were recommended to undergo breast MRI instead of undergoing a CEM-guided biopsy. This may have affected the biopsy rates, PPV3, and short-term follow-up rates of screening CEM. Fourth, the majority of the participants in our study were at above-average risk and had dense breasts. At our institution, these two groups (at above-average risk and with dense breasts) were the majority of participants undergoing CEM. Our results are therefore generalizable to women at increased risk of breast cancer but not necessarily to women at average risk of breast cancer. Last, our patient cohort was predominantly White (80.1%).

In conclusion, the cancer detection rate improved with screening contrast-enhanced mammography (CEM), depicting 90% of the cancers compared with 10% on low-energy (LE) images alone and 50% on LE images with whole-breast US. CEM is a suitable modality for screening, especially in women with dense breasts. Although cancer detection improved, CEM caused a higher number of recalls and false-positive biopsy results but with higher positive predictive value of biopsies performed. Supplemental whole-breast US may be averted in patients undergoing screening CEM because it does not add value to cancer detection and may increase false-positive recalls and biopsy results. Future studies should be performed in a more diverse population to understand whether our study results can be generalized across all races and ethnicities. Additional studies could also incorporate CEM-guided biopsies as part of the imaging algorithm because the availability of CEM-guided biopsy could reduce additional imaging with MRI.

Acknowledgments

Acknowledgments

The authors thank Joanne Chin, MFA, ELS, for editing this manuscript.

*

J.V.H. and T.A. contributed equally to this work.

Current addresses: 1Department of Radiology, Mayo Clinic, Rochester, Minn

2Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Amsterdam, the Netherlands

3Department of Radiology, New York-Presbyterian/Weill Cornell Medical Center, New York, NY

4Department of Radiology, Sheba Medical Center, Tel Hashomer, Israel

5Radnet Breastlink Women’s Imaging Beverly Hills, Los Angeles, Calif

6Department of Radiology, Columbia University, 161 Fort Washington Ave, Fl10, Suite 1052, New York, NY 10032

Supported in part by a National Institutes of Health/National Cancer Institute Cancer Center Support Grant (P30 CA008748).

Data sharing: Data generated or analyzed during the study are available from the corresponding author by request.

Disclosures of conflicts of interest: J.V.H. No relevant relationships. T.A. No relevant relationships. G.P.W. No relevant relationships. C.E.C. Consulting fees paid to author from Bayer. N.N. No relevant relationships. M.S.J. Honoraria for lectures from GE HealthCare. J.S.S. No relevant relationships.

Abbreviations:

CEM
contrast-enhanced mammography
FFDM
full-field digital mammography
LE
low energy
PPV
positive predictive value
PPV3
PPV of biopsies performed

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