Clinical trial NCT05797545: Comparison of Ultrasound and Breast MRI for Breast Cancer Detection
Official title: Comparison of Ultrasound and Breast MRI for Breast Cancer Detection Among Women With Dense Breasts and a Personal History of Breast Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Breast Neoplasms
Breast Cancer
Keywords: Mass Screening
Ultrasonography
Magnetic Resonance Imaging
Lead sponsor: Samsung Medical Center
Sponsor class: OTHER
First posted: 2023-04-04
Enrollment: 1464
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: SCREENING

Brief summary: The goal of this randomized clinical trial is to compare diagnostic results of secondary breast cancer surveillance using breast ultrasound abbreviated MRI and full protocol MRI.

Detailed description: Women who have been treated for breast cancer are at risk of ipsilateral local/regional recurrence or new primary cancers in the contralateral breast, which are associated with increased rates of distant metastases and breast cancer mortality. The goal of post-treatment imaging surveillance is to detect early second breast cancer, which permits interventions to improve survival and maintain quality of life.

Currently, most guidelines consistently recommend annual mammography for women with a personal history of breast cancer (PHBC). However, in women with dense breasts, mammographic sensitivity decreased from a level of 85.7%-88.8% in patients with almost entirely fatty tissue to 62.2%-68.1%. Even more, sensitivity of mammography was lower in women with a PHBC within the initial 5 years after primary breast cancer (PBC) treatment. In addition, dense breasts lead to an increased percentage of interval cancer. Thus, the need for a better surveillance modality has emerged.

In this context, breast US may be considered as a supplemental screening modality because it is widely available, does not need contrast agents, and is of relatively lower cost . A few studies indicate that adding screening US to mammography reduced interval cancer rates for women with dense breasts and enable detection of early-stage cancers at an average of 4.2 cancers per 1000 US examinations. As an another candidate, breast MRI shows high sensitivity and offers the highest cancer detection rate but its routine usage in women with a PHBC is still on debate.

Another possible imaging modality is breast magnetic resonance imaging (MRI). Current National Comprehensive Cancer Network (NCCN) guidelines suggest annual screening with mammography and MRI is recommended for ① women with Breast Cancer Susceptibility Gene (BRCA1 or BRCA2) mutations, ② first-degree family members of carriers of BRCA mutations, ③ women with a lifetime risk of breast cancer greater than 20% based on family history, and ④ women have radiotherapy for thorax at the age of 10-30 years and ⑤ women diagnosed with lobular carcinoma in situ (LCIS), atypical ductal hyperplasia (ADH), or atypical lobular hyperplasia (ALH) by previous biopsy. And, this is based on the results of existing single-center or multi-center prospective studies. Women who underwent breast-conserving surgery for breast cancer before the age of 50 were added to the 2018 new MRI screening group of the American College of Radiology (ACR), and their secondary breast cancer risk is 20% or more. Most women with a history of breast cancer have an intermediate risk (\>15% but \<20%) of developing breast cancer. Therefore, when most patients are not in the high-risk group, performing conventional MRI (full-protocol MRI, FP-MRI) for all postoperative examinations is not appropriate in terms of cost and time.

Abbreviated MRI (AB-MRI), introduced relatively recently, is a method designed to increase accessibility by reducing time and cost by selectively capturing only some sequences in FP-MRI. Sequence composition can be adjusted in various ways, and image acquisition must be completed within 10 minutes. A number of studies have demonstrated that AB-MRI has comparable diagnostic results to FP-MRI. The most recent paper published in Korea compared the scores of 726 patients with AB-MRI and FP-MRI by performing propensity score matching. The results were comparable in sensitivity, and AB-MR was significantly higher in specificity. Other indicators such as interval cancer rate or Breast Imaging Reporting \& Data System (BI-RADS) Category 3 rate did not show significant differences between the two groups. However, all studies are retrospective and there are no prospective data. Since the reported scores of AB-MRI and FP-MRI are comparable, it is difficult to test because the sample size is larger than 18,000 in order to perform a non-inferiority test on diagnostic scores. The purpose of this study was to compare the diagnostic results of secondary breast cancer surveillance using mammography, ultrasound, and MRI in a prospective multicenter study.

Eligibility criteria: Inclusion Criteria:

* Women aged 20-75 with a history of breast cancer (in situ carcinoma or invasive breast cancer \[stage 0-3\])
* Women with a negative resection margin in the pathology results of the last surgical specimen from past breast cancer
* Women with dense breasts with pattern C (heterogeneously dense) or D (extremely dense breasts) using AI-based Lunit INSIGHT for Mammography (version 1.1.4.3, Lunit Inc.) in the most recent mammography
* Women who have not had a breast imaging test within 6 months
* Women who agreed to undergo regular annual mammography, breast ultrasound, and breast MRI
* If mammography, ultrasound, or breast MRI was performed within the last 1 year, the most recent test result is normal or positive (BI-RADS 1 or 2)

Exclusion Criteria:

* Patients with symptoms related to current breast cancer or breast cancer recurrence (palpable mass, bloody or transparent nipple secretion, palpable mass in the axillary region, abnormal skin changes in the breast or nipple)
* If you have been diagnosed with regional recurrence (axillary lymph nodes, supraclavicular and subclavian lymph nodes, internal mammary lymph nodes, etc.) or distant metastases
* In case of bilateral total mastectomy
* If women are receiving chemotherapy for cancer in other organs
* Women during pregnancy or lactation
* Glomerular filtration rate \< 30 mL/min/1.73m2, or patients with renal insufficiency on dialysis
* If women have severe claustrophobia
* If women have a metal prosthesis that is not suitable for MR (e.g. breast tissue expander, etc.)
* If there is a history of severe contrast agent side effects (e.g., anaphylactoid reaction, dyspnea, etc.)

Primary outcomes:
measure: Cancer detection rate (CDR)
timeFrame: The results of pathology tests or imaging or clinical follow-up tests 1 year after the 2nd round screening were used.
Secondary outcomes:
measure: Abnormal interpretation rate (AIR)
timeFrame: The results of pathology tests or imaging or clinical follow-up tests 1 year after the 2nd round screening were used.
measure: Sensitivity
timeFrame: The results of pathology tests or imaging or clinical follow-up tests 1 year after the 2nd round screening were used.
measure: Specificity
timeFrame: The results of pathology tests or imaging or clinical follow-up tests 1 year after the 2nd round screening were used.
measure: Positive predictive value
timeFrame: The results of pathology tests or imaging or clinical follow-up tests 1 year after the 2nd round screening were used.
measure: Negative predictive value
timeFrame: The results of pathology tests or imaging or clinical follow-up tests 1 year after the 2nd round screening were used.
measure: Interval cancer rate
timeFrame: The results of pathology tests or imaging or clinical follow-up tests 1 year after the 2nd round screening were used.
measure: Patient reported outcomes (PRO) based on patient discomfort.
timeFrame: Patient questionnaires will be collected at time points of clinic visits for study, assessed up to 3 months.
measure: Patient reported outcomes (PRO) based on patient preference.
timeFrame: Patient questionnaires will be collected at time points of clinic visits for study, assessed up to 3 months.
Other outcomes:
Locations:
city: Busan
country: Korea, Republic of
facility: Inje University Busan Paik Hospital
state: BusanJin-Gu
city: Seoul
country: Korea, Republic of
facility: Samsung Medical center
state: Gangnam-gu
city: Seoul
country: Korea, Republic of
facility: Ewha Womans University Medical Center
state: Yangchun-gu
city: Seoul
country: Korea, Republic of
facility: Soon Chun Hyang University Hospital Seoul
state: Yongsan-Gu
Study officials:
affiliation: Samsung Medical Center
name: Eun Sook Ko, M.D., Ph.D.
role: STUDY_CHAIR
affiliation: Ewha Womans University
name: Jin Jung, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Inje University
name: Yung Mi Park, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Soon Chun Hyang University
name: Yun woo Jang, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: