Clinical trial NCT04619186: Diffusion-Weighted MRI for Breast Cancer Screening in Women With a Personal History of Breast Cancer
Official title: Comparison of Diffusion-Weighted MRI and Mammography Alone or Combined Mammography and Ultrasonography for Screening Women With a Personal History of Breast Cancer (DIMRISC-2 Study)
Study type: OBSERVATIONAL
Overall status: SUSPENDED
Conditions: Breast Cancer
Lead sponsor: Seoul National University Hospital
Sponsor class: OTHER
First posted: 2020-11-06
Enrollment: 1694
Sex: FEMALE
Minimum age (years): 25
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Women who underwent breast conservation therapy or mastectomy and at increased risk of an interval second breast cancer

Brief summary: Women with personal history of breast cancer (PHBC) are at risk of developing second breast cancers in the conserved and contralateral breast. Because early detection of second breast cancers at the asymptomatic phase can improve relative survival by 17-28%, guidelines recommend annual mammography screening in women with PHBC. However, lower sensitivity and higher interval cancer rates are observed in women with a PHBC compared with women without, especially in women 50 years or younger and those with dense breasts. In a multicenter comparison study of 754 women, MRI screening detected 3.8 additional cancers and ultrasonography detected 2.4 additional cancers, and increased sensitivity over mammography alone. However, the use of breast MRI is limited not only by high costs and long examination time but also by high false-positive findings. In addition, the use of intravenous gadolinium-based contrast agent is contraindicated in women with renal impairment or contrast material allergy contrast. Supplemental ultrasonography in patients with PHBC reports lower sensitivity with high interval cancer rate. Thus, there is a need to develop a more safe, accurate, and cost-effective supplemental imaging modality for screening in women with PHBC. Diffusion-weighted (DW) MRI is an unenhanced fast, functional modality that measures the movement of water molecules to create tissue contrast. Breast malignancies exhibit hindered diffusion and appear hyperintense on DW MRI with low apparent diffusion coefficient (ADC) compared to normal surrounding tissue. Multiple studies have shown that the use of DW MRI can significantly reduce the false positives and unnecessary benign biopsy of breast MRI. Several studies have shown that DW MRI has a potential to detect mammography occult breast cancers with less false positives compared to ultrasonography. These observations have led to the consideration of utilizing DW MRI to screen women with PHBC. In Diffusion-weighted MRI for Breast Cancer Screening (DIMRISC-2) study, we hypothesized that the screening performance of high-resolution DW MRI at 3.0 T should be superior to mammography alone or combined mammography and ultrasonography in women with PHBC. In our institution, alternating conventional imaging and DW MRI screening is offered for patients who have undergone breast surgery and at increased risk of an interval second breast cancer.

Detailed description: * Primary objective: to compare the screening performance of DW MRI versus mammography alone or combined mammography and ultrasonography in women with PHBC.
* Secondary objective: to compare the tumor and patient characteristics detected by DW MRI and combined mammography and ultrasonography in women with PHBC.
* This is a prospective, single center, observational cohort study.
* A total of 1694 women will be enrolled in this study.
* Two latest 3.0 T MRI scanners with dedicated 16- or 18-channel bilateral breast coil are used for DW MRI. For DW MRI screening, the high-resolution echo-planar imaging sequence is designed to have an in-plane resolution of 1.3 x 1.3 mm and a slice thickness of 3 mm. Three b values of 0, 800, and 1200 sec/mm2 are used and ADC maps are generated based on the b=0 and 800 sec/mm2 DW MRI data. The DW MRI images are reconstructed into single summation images with maximum-intensity projections (MIPs) in the sagittal and axial planes. In addition, T1-weighted imaging sequence is also obtained with in-plane resolution of 1.0 x 1.0 mm and a slice thickness of 1 mm.
* All patients with PHBC undergo digital two-dimensional mammography and physician-performed whole-breast ultrasonography on the same day. DW MRI and conventional imaging (mammography and ultrasonography) are alternatively scheduled at 6-month intervals and the order has been randomized.
* Mammography alone, combined mammography and ultrasonography, and DW MRI will be interpreted independently according to the Breast Imaging Reporting and Data System (BI-RADS) and likelihood of malignancy (Score range, 0%-100%) by trained radiologists. DW MRI interpretation guidelines to be used in this study are based on both qualitative and quantitative assessments. Radiologists are required to successfully complete a training case series of 100 DW MR studies prior to interpreting the DW MRI.
* A negative examination result is defined as a final assessment BI-RADS category of 1, 2, 3 and a positive examination result is defined as a final assessment BI-RADS category of 4 or 5.
* Biopsies of DW MRI-detected lesions are performed under ultrasonography guidance whenever possible or with MR guidance if there is no correlative ultrasonography finding. Pathology of core or surgical biopsy and 1 year follow up is the reference standard.

Eligibility criteria: Inclusion Criteria:

1. Women over 25 years of age at the time of enrollment
2. Women who underwent breast conservation therapy or mastectomy and at increased risk of an interval second breast cancer (Age \<50 at first cancer diagnosis; Breast density BI-RADS category 3 and 4; First degree family history; First breast cancer was an interval cancer or symptomatic presentation; First breast cancer was grade 2, 3 or ER and PR negative)

Exclusion Criteria:

1. Women with signs or symptoms of breast cancer
2. Women who had bilateral mastectomy

4. Women who had known metastatic disease 5. Pregnant or lactating women 6. Women with claustrophobia or metallic foreign body

Primary outcomes:
measure: Cancer detection rate (CDR)
timeFrame: Baseline to up to 1 year
Secondary outcomes:
measure: Sensitivity
timeFrame: Baseline to up to 1 year
measure: Specificity
timeFrame: Baseline to up to 1 year
measure: Recall rate
timeFrame: Baseline to up to 1 year
measure: Positive predictive value (PPV)
timeFrame: Baseline to up to 1 year
measure: Accuracy
timeFrame: Baseline to up to 1 year
measure: Interval cancer rate
timeFrame: Baseline to up to 1 year
measure: Characteristics of detected cancers
timeFrame: Baseline to up to 1 year
measure: Characteristics of women with DW-MRI detected cancer
timeFrame: Baseline to up to 1 year
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
Study officials:
affiliation: Seoul National University Hosptial
name: Woo Kyung Moon, MD, PhD
role: STUDY_CHAIR
References:
citation: Ha SM, Chang JM, Lee SH, Kim ES, Kim SY, Kim YS, Cho N, Moon WK. Detection of Contralateral Breast Cancer Using Diffusion-Weighted Magnetic Resonance Imaging in Women with Newly Diagnosed Breast Cancer: Comparison with Combined Mammography and Whole-Breast Ultrasound. Korean J Radiol. 2021 Jun;22(6):867-879. doi: 10.3348/kjr.2020.1183. Epub 2021 Apr 1.