Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Carcinoma

Breast Neoplasms

Breast Diseases

Skin Diseases

Patients undergo a clinical breast examination and a diagnostic mammogram with or without targeted breast ultrasound to the index cancer as part of their standard of care preoperative work-up. As part of the research study, patients receive contrast agent IV and then undergo a CESM with DBT over 30 minutes. Patients also receive a contrast agent, gadolinium, IV and undergo bilateral breast CE-MRI over 10 minutes.

Contrast Agent

Digital Tomosynthesis Mammography

Dual-Energy Contrast-Enhanced Digital Spectral Mammography

Mary Yamashita, MD

This pilot clinical trial studies how well contrast enhanced spectral mammography works with digital breast tomosynthesis in imaging patients with newly diagnosed breast cancer. Contrast enhanced spectral mammography uses a special dye that is injected into the veins before mammogram images are taken. Digital breast tomosynthesis uses multiple x-ray pictures to produce a 3-dimensional rendering of the entire breast. Contrast enhanced spectral mammography with digital breast tomosynthesis may highlight areas of concern within the breast in more detail than a standard mammogram and improve the accuracy of tumor size.

PRIMARY OBJECTIVES:

I. To compare the index lesion size (the largest diameter) from each of the four readings (standard of care 2 dimensional \[D\], magnetic resonance imaging \[MRI\], contrast enhanced spectral mammography \[CESM\], 3D) to gold standard index lesion size from surgical pathology (the largest diameter).

II. To document the additional ipsilateral and contralateral breast cancer lesions detected by the MRI, CESM, and 3D readings listed above.

OUTLINE:

Patients undergo a clinical breast examination and a diagnostic mammogram with or without targeted breast ultrasound to the index cancer as part of their standard of care preoperative work-up. As part of the research study, patients receive contrast agent intravenously (IV) and then undergo a CESM with digital breast tomosynthesis (DBT) over 30 minutes. Patients also receive a contrast agent, gadolinium, IV and undergo bilateral breast contrast enhanced (CE)-MRI over 10 minutes.

After completion of study, patients are followed up within 24-96 hours.

Contrast Enhanced Spectral Mammography With Digital Breast Tomosynthesis For Patients With Newly Diagnosed Breast Cancer

Emerging Tools in the Detection of Breast Cancer: Comparison of Contrast Enhanced Spectral Mammography With Digital Breast Tomosynthesis to Conventional Imaging Techniques Including Contrast Enhanced Magnetic Resonance Imaging and 2D Mammography With or Without Targeted Ultrasound

Intra-class correlation will be used to assess the agreement of index lesion size from each imaging reading to the gold standard (histopathology at surgery). Bland-Altman plot will be used to illustrate the pattern of difference between each reading and the gold standard.

National Cancer Institute (NCI)

University of Southern California

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Micronutrients

Anti-Infective Agents

All Drugs and Chemicals

Iodine

Cadexomer iodine

Patient receive iodinated contrast agent IV and undergo CEM. Patients who have not undergone DBT as part of their screening or diagnostic imaging within 3 month, undergo DBT. Patients medical records are reviewed.

Contrast-Enhanced Mammography

Electronic Health Record Review

Iodinated Contrast Agent

Olena Weaver

This clinical trial investigates contrast-enhanced mammography (CEM) in detecting breast cancer. CEM is similar to standard mammography, but it includes an injection of an iodine-based contrast, which makes tissue and blood vessels more visible in scans. Diagnostic procedures, such as CEM, may increase the chance of finding breast cancers and decrease the risk of having unnecessary biopsies.

PRIMARY OBJECTIVE:

I. To compare the accuracy of CEM and low energy (LE) images (equivalent of full field digital mammogram \[FFDM\] as the standard of care) for the detection of additional cancer sites in the affected breast and in the contralateral breast.

SECONDARY OBJECTIVES:

I. To evaluate the sensitivity, specificity, positive and negative predictive value of CEM compared to LE CEM images (FFDM equivalent), digital breast tomosynthesis (DBT) and ultrasound for the detection of additional malignant lesions in the ipsilateral and contralateral breast.

II. To evaluate the difference of the index cancer size estimation among CEM, LE images, DBT, and ultrasound compared to pathology measurements as the ground truth.

III. To evaluate the incremental cancer detection rate provided by CEM, DBT, and ultrasound (US) compared to the outside facility (OSF) diagnosis.

EXPLORATORY OBJECTIVES:

I. To evaluate the rate of referral to breast magnetic resonance imaging (MRI) in the study cohort.

II. To evaluate the performance of MRI for breast cancer diagnosis and compare it with other imaging modalities of CEM, LE images, DBT, and US.

III. To evaluate the feasibility of CEM-guided biopsy of CEM-only detected lesions.

OUTLINE:

Patient receive iodinated contrast agent intravenously (IV) and undergo CEM. Patients who have not undergone DBT as part of their screening or diagnostic imaging within 3 month, undergo DBT. Patients medical records are reviewed.

After completion of study treatment, patients are followed up for 12 months.

Contrast-Enhanced Mammography for Breast Cancer Staging in Patients Referred for a Second Opinion

Added Value of Contrast Enhanced Mammography for Breast Cancer Staging in Patients Referred for a Second Opinion to a Tertiary Cancer Center

Defined as the number of concordant cases between CEM/low energy (LE) and pathologic evaluation divided by the total sample size. Will be estimated along with 95% confidence intervals; and compared between the modalities using the McNemar test or the weighted generalized score statistic proposed by Kosinski, if deemed appropriate. To account for multiple lesions, outcome variables will be analyzed using generalized liner mix models or extended McNemar's test, and additional analyses may be further performed if deemed appropriate.

M.D. Anderson Cancer Center

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Galactorrhea

Lactation Disorders

Puerperal Disorders

Pregnancy Complications

Urogenital Diseases

Female Urogenital Diseases

Female Urogenital Diseases and Pregnancy Complications

Patients receive iodine-based contrast agent IV then undergo CESM over 10-15 minutes. Patients who have not undergone standard of care DBT within 3 months from the study, also undergo DBT.

Contrast Enhanced Digital Mammography

Questionnaire Administration

Olena Weaver, MD

This clinical trial studies contrast enhanced spectral mammography (CESM) for the evaluation of pathologic nipple discharge. CESM is similar to standard mammography, but it includes an intravenous (by vein) injection of an iodine-based contrast, which makes tissue and blood vessels more visible in scans. The goal of this trial is to learn if CESM, is better than standard mammography in quickly and efficiently determining the cause of nipple discharge and detecting breast cancer, if present. CESM may increase the chance of finding breast cancers and lower the risk of having unnecessary biopsies.

PRIMARY OBJECTIVE:

I. To evaluate the added sensitivity of contrast enhancement of CESM (represented by the subtracted contrast images of CESM) compared to low energy \[LE\] images of CESM (full field digital mammogram \[FFDM\] equivalent) in detecting the causative lesion (invasive malignancy, ductal carcinoma in situ \[DCIS\], atypia, or papilloma) in patients with pathologic nipple discharge (PND).

SECONDARY OBJECTIVES:

I. To compare the sensitivity, specificity, negative predictive value, and positive predictive value of CESM versus DBT and ultrasound (US) in predicting invasive malignancy or DCIS in patients with PND.

II. To compare the accuracy of digital breast tomosynthesis (DBT) and LE in the detection of invasive malignancy or DCIS, as well as in the detection of the causative lesion.

III. To estimate the proportion of cases in which CESM affects the choice of the lesion targeted for a biopsy with any imaging modality.

IV. To evaluate the cancer detection rate and the outcomes (need for additional imaging, biopsies, and final pathologic results) of incidental CESM findings.

EXPLORATORY OBJECTIVES:

I. To evaluate the correlation of blood biomarkers and the presence of invasive cancer and DCIS on pathology in the study patients.

II. To evaluate the role of the CESM enhancement pattern in choosing a precise target for a stereotactic biopsy.

III. To evaluate the effect of CESM on the patient workflow by calculating the time from presentation to the definitive diagnosis.

IV. To evaluate the technical feasibility of using CESM- guided or CESM directed biopsies.

V. In patients who undergo a CESM targeted or CESM directed biopsy we will evaluate the upgrade rate of DCIS to invasive malignancy or high-risk lesions to in-situ or invasive cancer for those patients who will require surgery as a part of their routine clinical care.

VI. In those study patients who undergo breast MRI as a part of their clinical care, the sensitivity and specificity of magnetic resonance imaging (MRI) and CESM for the detection of causative lesions will be compared.

OUTLINE:

Patients receive iodine-based contrast agent intravenously (IV) then undergo CESM over 10-15 minutes. Patients who have not undergone standard of care DBT within 3 months from the study, also undergo DBT.

Contrast Enhanced Spectral Mammography for the Evaluation of Pathologic Nipple Discharge

Contrast Enhanced Spectral Mammography (CESM) for the Evaluation of Pathologic Nipple Discharge: A Pilot Study

Will be compared to low exposure (LE) images of CESM (full field digital mammogram equivalent) in detecting the causative lesion (invasive malignancy, ductal carcinoma in situ (DCIS), atypia, or papilloma) in patients with pathologic nipple discharge (PND).

Participants undergo DBT followed by AB-MR for under 10 minutes on the same day or within 24 hours at baseline and then after 1 year.

Participants undergo AB-MR for under 10 minutes followed by DBT on the same day or within 24 hours at baseline and then after 1year.

Contrast-enhanced Magnetic Resonance Imaging

Quality-of-Life Assessment

Christopher Comstock

This randomized phase II trial studies how well abbreviated breast magnetic resonance imaging (MRI) and digital tomosynthesis mammography work in detecting cancer in women with dense breasts. Abbreviated breast MRI is a low cost procedure in which radio waves and a powerful magnet linked to a computer and used to create detailed pictures of the breast in less than 10 minutes. These pictures can show the difference between normal and diseased tissue. Digital tomosynthesis mammography is a procedure that uses multiple x-rays pictures of each breast to produce a 3-dimensional rendering of the entire breast. Combined screening with abbreviated breast MRI and digital tomosynthesis mammography may be a better method to screen women with dense breasts.

PRIMARY OBJECTIVES:

I. To compare the rates of detection of invasive cancers between the initial abbreviated breast (AB)-magnetic resonance (MR) and digital tomosynthesis mammography (DBT).

SECONDARY OBJECTIVES:

I. To compare the positive predictive value (PPV) of biopsies, call back rates, and short-term follow up rates after AB-MR and DBT on both the initial and 1 year follow up studies.

II. To estimate and compare the sensitivity and specificity of AB-MR and DBT, using the 1 year follow up to define a reference standard.

III. To compare patient-reported short-term quality of life related to diagnostic testing with AB-MR and DBT using the Testing Morbidities Index.

IV. To compare willingness to return for testing with AB-MRI versus (vs) DBT within the recommended screening interval and explore factors associated with willingness to return for screening.

V. To compare the tumor biologies of invasive cancers and ductal carcinoma in situ (DCIS) detected on AB-MR and DBT.

VI. To estimate the incident cancer rate during 3 years following the year-1 AB-MR/DBT when patients return to standard screening.

OUTLINE: Participants are randomized to 1 of 2 arms.

ARM A (DBT, AB-MR): Participants undergo DBT followed by AB-MR for under 10 minutes on the same day or within 24 hours at baseline and then after 1 year.

ARM B (AB-MR, DBT): Participants undergo AB-MR for under 10 minutes followed by DBT on the same day or within 24 hours at baseline and then after 1 year.

After completion of study, patients are followed up at every 6 months for 3 years.

Abbreviated Breast MRI and Digital Tomosynthesis Mammography in Screening Women With Dense Breasts

Comparison of Abbreviated Breast MRI and Digital Breast Tomosynthesis in Breast Cancer Screening in Women With Dense Breasts

Safe harbor de-identified data corresponding to publications will be shared upon request

For each modality, the detection rate of invasive cancers is defined as the proportion of participants who had an invasive cancer detected by the modality at baseline and verified by pathology versus the total number of participants. In the out come measures table below, these proportions will be automatically calculated, multiplied by 100, and be presented as percentages (%).

Test Positive (T+): Biopsy recommended by imaging, defined as patients with at least one lesion rated BI-RADS 4 or 5 on image interpretation. Reference Standard Positive (RS+): Pathologically confirmed DCIS or invasive disease resultant from a positive test.

The 95% confidence interval for PPV of biopsy for each modality were derived from the GEE model using the appropriate estimable contrasts with robust standard errors

For DBT:

DBT: Call back is defined as having additional views or targeted ultrasound to evaluate DBT findings DBT: short term follow up (STFU) is defined as having at least one lesion rated BI-RADS 3 on DBT DBT: Additional imaging recommendation is defined as having either call back or STFU

For AB-MR:

Ab-MR: Call back does not apply to AB-MR and will not be evaluated Ab-MR: Short Term Follow-up (STFU) is defined as having at least one lesion rated BI-RADS 3 on AB-MR Ab-MR: Additional imaging recommendation is defined as having a STFU

Reference standard positive (RS+): breast cancer (invasive or DCIS) detected on the year 0 screening or reported at any time from the year 0 to the year 1 screening.

Reference standard negative (RS-): No breast cancer reported at any time from the year 0 to the year 1 screen.

Incomplete: No Year 1 imaging, and \<11 months of patient follow-up (\<330 days) after year 0 screen

Positive Test (T+) is defined as the imaging modality result is positive (BI-RADS 3-5), and the location of the finding is matches the location of the cancer indicated by the reference standard.

Negative Test (T-) will be estimated as the fraction of reference standard negative subjects for whom the imaging modality result was negative (BI-RADS 1-2).

95% confidence intervals for the sensitivity and specificity of each modality calculated using the Wilson method.

Testing Morbidities Index (TMI) scores \[0 (worst) to 100 (best) scale\] will be computed for abbreviated breast-magnetic resonance (MR) and digital tomosynthesis mammography (DBT) after the baseline screen.

The proportions of participants willing to return for screening with either test, AB-MRI only, DBT only, or not willing to return for either test will be estimated.

Polytomous logistic regression will be used to examine factors associated with willingness to return, including screen result, cancer status, and demographic characteristics.

Descriptive Analyses presenting the the distributions of Oncotype-DCIS scores by modality A low risk score is less than 39, and a high risk score is 55 or higher. A score of 39 to 54 is intermediate risk.

Breast cancer incidence will be estimated. Person-years will be measured.

For all invasive cancers detected during the study period, the NanoString PAM50 will be performed. The frequencies of cancer types determined by the NanoString analysis will be tabulated and compared. For DCIS, if the Oncotype-DCIS score was performed, the distributions of scores will be tabulated and compared.

ECOG-ACRIN Cancer Research Group

Serious Adverse Events (SAE), in addition to the standard definition include:

All Grade 5 events occurring within 30 days of imaging, regardless of attribution or unexpectedness All Grade 4 events occurring within 30 days of imaging that are unexpected and have an attribution of "Possible, Probable, Definite" All Grade 4 kidney adverse events All occurrences of Nephrogenic Systemic Fibrosis (NSF) or Nephrogenic Fibrosing Dermopathy (NFD) All Grade 5 events while on study

All participants scheduled for both DBT and AB-MR Note, because of the temporal proximity (generally the same day), it is not possible to attribute the adverse events either by arm or by an individual modality.

All Participants

Participants undergo DBT followed by AB-MR, for under 10 minutes, on the same day or within 24 hours at baseline and then after 1 year.

AB-MR: Contrast-enhanced Abbreviated Magnetic Resonance Imaging (MRI) DBT: Digital Tomosynthesis Mammography

Arm A (DBT, AB-MR)

Participants undergo AB-MR, for under 10 minutes, followed by DBT on the same day or within 24 hours at baseline and then after 1 year.

AB-MR: Contrast-enhanced Abbreviated Magnetic Resonance Imaging (MRI) DBT: Digital Tomosynthesis Mammography

Arm B (AB-MR, DBT)

Total

Age, Continuous

Female

Sex/Gender, Customized

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Menopausal Status

Breast density (baseline DBT)

Prior personal history of breast cancer

Director Clinical Research Administration

The proportion of participants who had an invasive cancer, verified by pathology, detected by each modality (the invasive cancer detection rates) will be made using exact McNemar's test.

Detection of Cancer based on results of Digital Breast Tomosynthesis (DBT) performed within 30 days following registration.

DBT and abbreviated -MR were performed on the same day and interpreted by two different radiologists, each blinded to the other modality. However, DBT and AB-MR were allowed to be performed within 24 hours of each other, as long as the radiologists remained blinded to the results of the other modality

Digital Breast Tomosynthesis (DBT)

Detection of Cancer based on results of abbreviated breast MR (AB-MR) performed within 30 days following registration.

DBT and AB-MR were performed on the same day and interpreted by two different radiologists, each blinded to the other modality. However, DBT and AB-MR were allowed to be performed within 24 hours of each other, as long as the radiologists remained blinded to the results of the other modality

Abbreviated Breast MR (AB-MR)

Screen-detected Invasive Cancer Verified by Pathology

Patients with at least one lesion rated BI-RADS 4 or 5 on image interpretation.

Biopsy Recommended by Digital Breast Tomography

Patients with at least one lesion rated BI-RADS 4 or 5 on Abbreviated MR interpretation.

Biopsy Recommended by AB-MR

Positive predictive value is calculated on patients with at least one lesion rated BI-RADS 4 or 5 on image interpretation (I.e., Biopsy recommended) and is the percentage of biopsy recommended by imaging test versus patients with cancer P(D+\|T+)

Positive Predictive Value (PPV) of Biopsies

The exact p-value from McNemar's test is reported for for comparing the DBT against the AB-MR short term follow-up rates

The exact p-value from McNemar's test is reported for for comparing the DBT against the AB-MR additional imaging rates

Call back

Short-term follow-up (subject-level)

Additional imaging recommendation

subjects requiring further assessment by DBT (i.e. either a call back or short term follow up (STFU)) Call back is defined as having additional views or targeted ultrasound to evaluate DBT findings STFU is defined as having at least one lesion rated BI-RADS 3 on DBT Additional imaging recommendation is defined as having either call back or STFU

DBT Additional Imaging Recommendation

subjects requiring further assessment by AB-MR Call back does not apply to AB-MR and will not be evaluated Short Term Follow-up (STFU) is defined as having at least one lesion rated BI-RADS 3 on AB-MR Additional imaging recommendation is defined as having a STFU

AB-MR Additional Imaging Recommendation

Call Back/Additional Imaging/Short-term Follow Rates for DBT and AB-MR

Sensitivity (T+|RS+)

Specificity (T-|RS-)

Results of the Digital Breast Tomography (DBT) interpretation

Test A: Digital Breast Tomography

Results of the Abbreviated MR interpretation

Test B: Abbreviated MR

of the 1444 women available for analysis 14 were missing reference standard information.

Prediction of Breast Cancer (Sensitivity and Specificity)

TMI component during exam

TMI component after exam

Subjects with Abbreviated MRI and completed PRO surveys.

Abbreviated MRI

Subjects with Digital Breast Tomosynthesis and completed PRO surveys.

Digital Breast Tomosynthesis

Participants with both DBT and MRI performed and completed PRO surveys

Change in Patient-reported Short-term Quality of Life Related to Diagnostic Testing

Subjects with Abbreviated MRI and completed PRO surveys and their willingness to be screened in the future

Abbreviated MRI Willingness to be Screened in the Future

Subjects with Digital Breast Tomosynthesis and completed PRO surveys and their willingness to be screened in the future

Digital Breast Tomosynthesis Willingness to be Screened in the Future

Subjects with Abbreviated MRI and completed PRO surveys and their willingness to be screened in the future if AB-MRI Detects More Cancer than Mammography or Ultrasound

Ab-MRI Future Screen if AB-MRI Detects More Cancer Than Mammography or Ultrasound

Subjects with DBT and completed PRO surveys and their willingness to be screened in the future if DBTDetects More Cancer than Mammography or Ultrasound

DBT Future Screen if DBT Detects More Cancer Than Mammography or Ultrasound

Subjects with AB-MR, DBT and completed surveys

Willingness to Return for Testing With Abbreviated Breast-magnetic Resonance (MR) Versus Digital Tomosynthesis Mammography (DBT)

Factors Associated With Willingness to Return for Screening

Ductal Carcinoma in Situ (DCIS) Detected on Abbreviated Breast-magnetic Resonance (MR) and Digital Tomosynthesis Mammography (DBT)

Year 1 Screen to 12 mo post screening

12 months to 24 months post study screening

24 months to 36 months study screening

All participants scheduled for both DBT and AB-MR Estimated incident cancer rate (95% CI): interpreted as number of incident cancers per 1,000 person-years

All eligible subjects who received both Ab-MR and DBT at year 0 and year 1

Incident Cancer Rate

Tumor Biologies of Invasive Cancers and Ductal Carcinoma in Situ (DCIS) Detected on AB-MR and DBT

Overall Study

Technetium Tc 99m Sestamibi

Radiopharmaceuticals

Participants undergo DBT and MBI at year 0 and year 1 screening.

Scintimammography

Carrie B. Hruska, M.D.

This study compares molecular breast imaging (MBI) and digital breast tomosynthesis (DBT) in screening patients with dense breast tissue. Breast imaging may help doctors find breast cancer sooner, when it may be easier to treat. Molecular breast imaging (MBI) uses an injection of a small amount of radioactive material that is taken up in tissues of the body that are actively changing, such as breast cancer. A specialized camera, called a gamma camera, takes pictures of the gamma rays emitted by this material. MBI may detect cancers that are not visible on mammograms. This study may help researchers determine how MBI testing compares to DBT screening.

PRIMARY OBJECTIVE:

I. To compare the rate of detection of invasive cancers between digital breast tomosynthesis (DBT) alone versus (vs.) the combination of DBT with supplemental MBI at year 0 screening.

SECONDARY OBJECTIVES:

I. To compare the invasive cancer detection rates of DBT alone vs. MBI alone at year 0 screening.

II. To compare the screening performance metrics of sensitivity, specificity, recall rate, biopsy rate, positive predictive value and negative predictive value for DBT and MBI.

III. To compare tumor characteristics of all cancers (invasive and noninvasive) detected on DBT and MBI, including size, nodal status, and molecular subtype.

IV. To assess the reduction in advanced cancer rate with incorporation of MBI screening by comparing advanced cancer rate observed at year 1 screening relative to that at year 0.

V. To assess the rate of interval cancers with incorporation of MBI screening. VI. To examine the relative performance of DBT and MBI within subgroups categorized by breast cancer risk.

OUTLINE:

Participants undergo DBT and MBI at year 0 and year 1 screening.

Molecular Breast Imaging and Digital Breast Tomosynthesis in Screening Patients With Dense Breast Tissue

Density MATTERS [Molecular Breast Imaging (MBI) And Tomosynthesis To Eliminate the ReServoir]

Will compare the rate of detection of invasive cancers between DBT alone versus (vs.) the combination of digital breast tomosynthesis (DBT) with supplemental molecular breast imaging (MBI) at year 0 screening. For each modality, the detection rate of invasive cancers will be estimated as the proportion of participants in the analysis set who had an invasive cancer detected by the modality and verified by pathology. Because of the paired design, the primary comparison of the invasive cancer detection rates will be made using a 2-sided McNemar's test at statistical significance level alpha= 0.05.

Will compare the rate of detection of invasive cancers between DBT alone vs. MBI alone at Year 0 screening. The comparison will be based on a 2-sided McNemar's test at statistical significance level alpha= 0.05.

Sensitivity will be estimated for each modality as the proportion of women with breast cancer who have true positive test results. Will be analyzed to compare performance of DBT alone vs. MBI alone, and DBT alone vs. the combination of DBT with supplemental MBI. Uncertainty in the estimate of sensitivity will be quantified through a two-sided 95% confidence interval (CI) based on the binomial distribution. If a sufficient number of radiologists interpret exams from multiple patients with breast cancer, secondary analysis may also include a 95% CI and chi-squared test adjusted for clustering of results within radiologist to allow generalization to both the population of patients and the population of radiologists.

Specificity will be estimated as the proportion of women without breast cancer who have TN test results. Will be analyzed to compare performance of DBT alone vs. MBI alone, and DBT alone vs. the combination of DBT with supplemental MBI.

Recall rate (defined as the proportion of patients recalled from the screening test for diagnostic workup among the total number of patients screened) will be estimated employing analytical strategies similar to sensitivity and specificity. McNemar's test will be used to compare rates between two modalities. Will be analyzed to compare performance of DBT alone vs. MBI alone, and DBT alone vs. the combination of DBT with supplemental MBI.

Biopsy rate (defined as the proportion of patients in whom biopsy is generated from a particular modality among the total number of patients screened) will be estimated employing analytical strategies similar to sensitivity and specificity. McNemar's test will be used to compare rates between two modalities. Will be analyzed to compare performance of DBT alone vs. MBI alone, and DBT alone vs. the combination of DBT with supplemental MBI.

Predictive values will be estimated for each modality based on data pooled across radiologists. Positive predictive value (PPV)1 (the proportion of patients with breast cancer among patients with abnormal screening examinations), PPV3 (the proportion of breast cancers diagnosed among biopsies performed), and negative predictive value (NPV) (the proportion of patients without breast cancer among those with normal screening examinations) will be determined. Will be analyzed to compare performance of DBT alone vs. MBI alone, and DBT alone vs. the combination of DBT with supplemental MBI.

Will compare tumor characteristics of all cancers (invasive and noninvasive) detected on DBT and MBI, including size, nodal status, and molecular subtype. The analysis comparing tumor characteristics will be descriptive. Size, nodal status, and molecular subtype (including estrogen and progesterone receptor status, HER-2 status, Ki-67 and Oncotype DX score as available) will be abstracted from clinical final pathology reports from all biopsies and surgeries performed. The distribution of sizes will be summarized by ordinary numeric (e.g., means, standard deviations \[SDs\], range) and graphical (e.g., histograms, density smoothers) summaries. Descriptive summaries of the lesions identified with MBI but not DBT and vice versa will also be calculated to understand the differences in performance should one be identified.

Will assess whether the incorporation of MBI screening reduces advanced cancer rate, the rate of advanced cancers detected at Year 1 screening will be compared to the rate at Year 0 screening. The rates of advanced cancers, together with their respective 95% confidence intervals, will be estimated for Year 0 and Year 1. Comparison in the rates between Year 0 and Year 1 will utilize the test of two proportions based on exact binomial distributions.

We will estimate the rate of interval cancers from our study and provide a 95% confidence interval.

The relative performance of the screening modalities (sensitivity and specificity) will be characterized separately, within subgroups of patients defined by various levels of risk. The statistical power to discern differential performances of the screening modalities among different risk subgroups may be limited due to the restricted sample size in these subgroup analyses.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Contrast Enhanced Spectral Mammography With Digital Breast Tomosynthesis For Patients With Newly Diagnosed Breast Cancer	NCT03176979	Breast Carcinom...	Contrast Agent Digital Tomosyn... Dual-Energy Con...	18 Years -	University of Southern California
Contrast-Enhanced Mammography for Breast Cancer Staging in Patients Referred for a Second Opinion	NCT05036083	Breast Carcinom... Invasive Breast...	Contrast-Enhanc... Digital Tomosyn... Electronic Heal... Iodinated Contr...	18 Years -	M.D. Anderson Cancer Center
Contrast Enhanced Spectral Mammography for the Evaluation of Pathologic Nipple Discharge	NCT05056844	Breast Carcinom...	Contrast Enhanc... Digital Tomosyn... Iodinated Contr... Questionnaire A...	25 Years - 85 Years	M.D. Anderson Cancer Center
Abbreviated Breast MRI and Digital Tomosynthesis Mammography in Screening Women With Dense Breasts	NCT02933489	Asymptomatic	Contrast-enhanc... Digital Tomosyn... Quality-of-Life... Questionnaire A...	40 Years - 75 Years	Eastern Cooperative Oncology Group
Molecular Breast Imaging and Digital Breast Tomosynthesis in Screening Patients With Dense Breast Tissue	NCT03220893	Breast Carcinom...	Digital Tomosyn... Scintimammograp...	40 Years - 75 Years	Mayo Clinic
Abbreviated Breast MRI and Digital Tomosynthesis Mammography in Screening Women With Dense Breasts	NCT02933489	Asymptomatic	Contrast-enhanc... Digital Tomosyn... Quality-of-Life... Questionnaire A...	40 Years - 75 Years	Eastern Cooperative Oncology Group
Contrast Enhanced Spectral Mammography for the Evaluation of Pathologic Nipple Discharge	NCT05056844	Breast Carcinom...	Contrast Enhanc... Digital Tomosyn... Iodinated Contr... Questionnaire A...	25 Years - 85 Years	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for digital tomosynthesis mammography