Breast Cancer
Conditions
Keywords
breast cancer supplemental screening, breast density, contrast-enhanced mammography, screening mammography
Brief summary
There are women for whom a screening breast MRI is clinically recommended, but not feasible either due to patient factors (body habitus, pacemaker or other implant, claustrophobia) or access (cost, other constraints). Contrast-enhanced mammography (CEM) is a potential alternative to MRI for screening that uses updated standard mammography equipment to obtain low- and high-energy images after intravenous injection of iodinated contrast (as used in CT scanning). The investigators seek to validate screening CEM as an alternative to screening MRI.
Detailed description
This is a prospective study designed to evaluate the role of contrast enhanced mammography (CEM) in screening for breast cancer. The overarching goal of the research program is to improve cancer detection on screening, particularly in women with dense breasts. MRI depicts more cancers than other screening methods, including ultrasound. MRI is proven to both improve cancer detection and reduce clinically detected cancers ("interval cancers") after a negative screening mammogram in women with dense breasts. PA Senate Bill 595, signed into law June 30, 2020, requires insurance carriers to provide coverage for supplemental screening with MRI or ultrasound for a variety of indications. Relative to the number of women who may benefit from screening MRI, there is a shortage of equipment/capacity. Further, nearly half of women cannot have an MRI for medical or other reasons, such as claustrophobia, implanted devices, body habitus, or cost (deductible and copay apply even with the new legislation). Contrast-enhanced mammography (CEM) appears to have similar performance to MRI but has not been widely validated, particularly for screening. In order to lay the foundation for improved screening of women with dense breasts, the investigators seek to offer screening CEM as an alternative to MRI for women who meet guidelines for screening MRI but are unable to have MRI.
Interventions
supplemental breast cancer screening with contrast-enhanced mammography
supplemental breast cancer screening with contrast-enhanced mammography
Sponsors
Wendie Berg
PA Breast Cancer Coalition
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SCREENING
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
30 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
1. Asymptomatic women under age 75 who are recommended for annual screening MRI and mammography based on current criteria: 1. Women known to be at high risk for breast cancer because of known or suspected pathogenic mutation, prior chest radiation therapy at least 8 years earlier and before age 30, or estimated lifetime risk of at least 20% based on family history/prior biopsy history (22), between age 30 and 75. 2. Women with extremely dense breasts age 40-75 (about 7% of the screening population (1)) (12). 2. Women with lobular carcinoma in situ (1% of women biopsied each year; about 0.06% of our screening population) beginning the year after diagnosis. 3. Women with a personal history of breast cancer diagnosed by age 50 or with dense breasts (21), beginning the year after diagnosis (will be recruited under separate ongoing TOCEM protocol). 4. Women with heterogeneously dense breasts and any family history of breast cancer (about 36% of the screening population has dense breasts and about 20% have a family history of breast cancer) who do not meet current high-risk criteria, beginning at age 40 or ten years prior to the age of the youngest relative but not before age 30. Participants are expected to have medical or other reasons that they are not able to have screening breast MRI.
Exclusion criteria
1. Under age 30 or over age 75. 2. Pregnant or breast feeding. 3. Breast implants. 4. Breast surgery within the prior 12 months. 5. Breast signs or symptoms (lump, nipple discharge, nipple retraction, or being followed for breast abnormality on prior imaging). 6. Currently undergoing any type of systemic chemotherapy for cancer (excludes oral endocrine therapy such as aromatase inhibitors or tamoxifen). 7. Reduced kidney function with eGFR \< 45 mL/min.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cancer Detection Rate (CDR) Per 1,000 Screenings | 1.5 years | Cancer detection rate per 1,000 screenings with CEM compared to standard mammography/tomosynthesis (DBT) alone. Interpretation and performance outcomes from the primary reader were compared between standard-of-care DBT examinations interpreted alone and DBT examinations interpreted with the addition of CEM. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| False Positive Recall Rates | 1.5 years | To assess changes in false positive recall rates from CEM. DBT false-positive findings for primary observer (usual care) vs DBT and CEM false positive findings for primary observer |
| Biopsy Rate | 1.5 years | To assess changes in the biopsy rate after the addition of CEM. DBT biopsy rate for primary observer (usual care) vs DBT and CEM biopsy rate for primary observer. |
| Positive Predictive Value of Recall (PPV1) | 1.5 years | To assess changes in positive predictive value of recall (PPV1) after the addition of CEM. DBT PPV1for primary observer (usual care) vs DBT and CEM PPV1 for primary observer. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORWendie Berg, MD, PhD
University of Pittsburgh
Participant flow
Pre-assignment details
All participants who signed informed consent were assigned to a single screening contrast enhanced mammography (CEM) examination with clinical standard-of-care tomosynthesis (DBT).Two radiologists (one primary) evaluated each pair of examinations by sequentially interpreting each of DBT and CEM in opposing order, initially blinded to the other modality.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 57 Years |
| Body Mass Index 25 kg/m^2 or less | 325 Participants |
| Body Mass Index > 25 to 30 kg/m^2 | 159 Participants |
| Body Mass Index > 30 kg/m^2 | 117 Participants |
| Breast Density Extremely dense | 51 Participants |
| Breast Density Fatty | 0 Participants |
| Breast Density Heterogeneously dense | 473 Participants |
| Breast Density Scattered | 77 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 601 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Menopausal status Perimenopausal | 101 Participants |
| Menopausal status Postmenopausal | 400 Participants |
| Menopausal status Premenopausal | 100 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 9 Participants |
| Race (NIH/OMB) Black or African American | 20 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 570 Participants |
| Sex: Female, Male Female | 601 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 615 | 0 / 615 |
| other Total, other adverse events | 5 / 615 | 0 / 615 |
| serious Total, serious adverse events | 0 / 615 | 0 / 615 |
Outcome results
None listed