Abstract P3-03-23: Surveillance breast magnetic resonance findings in asymptomatic CDH1 variant carriers
Authors: Gamble Lauren A. , Teke Martha , Fridling Jeremy , Samaranayake Sarah G. , Redd Bernadette , Blakely Andrew , Davis Jeremy L. 
Published: March 2022

Introduction: An estimated 20% of breast cancers are attributed to a germline mutation; BRCA1/2 gene variants are most well-known and account for almost 40% of hereditary breast cancers. Families that carry CDH1 germline pathogenic or likely pathogenic (P/LP) variants have increased risk of developing diffuse type gastric cancer and invasive lobular breast cancer (LBC). Specifically, the lifetime risk of developing breast cancer due to CDH1 is estimated to be 39-55%. LBC is characterized by an infiltrative growth pattern, which results in decreased detection sensitivity by mammography. Consensus guidelines recommend annual breast surveillance with magnetic resonance (MR) imaging alternating with mammography every six months between 30 and 50 years of age. However, this patient population is less studied, particularly regarding breast cancer surveillance. We sought to determine the incidence of abnormal breast MR findings in women with CDH1 P/LP variants, identify the median age that abnormalities were discovered, and evaluate for concordance with mammogram, ultrasound, and pathology. Methods: Patients with CDH1 P/LP variants were enrolled in a prospective study of hereditary gastric cancers at a single institution between January 2017 and May 2021. Patient demographics, breast imaging findings, breast pathology, and detailed family pedigree of breast and gastric cancers were analyzed. Results: 283 patients with CDH1 P/LP variants were enrolled, of whom 154 were women. Thirty-one (31/154) women were diagnosed with breast cancer prior to enrollment and 30 were outside the recommended breast MR surveillance window (&lt;30 or &gt;50 years). Data were available on 64 women who underwent at least one surveillance breast MR. The majority (58/64, 91%) were Caucasian, 48 (75%) had family history of breast cancer and 48 (75%) had a family history of gastric cancer. The median age of first surveillance MR was 44 (range 25-73) with a median age of 45 at CDH1 diagnosis. Of the 64 women who underwent surveillance breast MR, a total of 106 scans were performed; 32 patients (48%) had one MR, 14 (1%) had two, and 18 (28%) had ≥3. Most women (34/64, 53%) demonstrated benign or normal findings (BIRADS 1 or 2). Abnormal or incomplete imaging was found in 19 women (BIRADS 0, 3, 4, 5). Most women (18/19, 94%) with a breast abnormality were discovered during the first surveillance scan, whereas one woman had an abnormality on subsequent imaging. Four (4/19) women demonstrated multifocal lesions and four had bilateral enhancing lesions. The average size of contrast-enhancing lesion was 1.3cm (0.3-4.4cm). Further diagnostic workup was available on 15 women, of whom four had invasive disease resulting in an overall cancer detection rate of 6% (4/64) and a false positive rate of 73% (11/15). Of the four women ultimately diagnosed with LBC, three had an initial BIRADS 4 and one was BIRADS 0. Of the 11 women who did not have invasive disease, six initially had BIRADS 0 readings, two BIRADS 3, and three BIRADS 4. Conclusions: In a cohort of women with CDH1 P/LP variants the overall detection rate of abnormal lesions on surveillance MR was 29% and the cancer detection rate was 6%. When follow-up imaging and/or biopsy was available the concordance rate was 33%. The median age of first surveillance MR and first lesion discovered were the same, suggesting the recommendation for breast cancer surveillance starting at age 30 is appropriate. These data support the use of alternating breast MR with mammogram and highlight the need for prompt diagnosis of germline CDH1 variants in order to promote early breast cancer detection.

Citation Format: Lauren A. Gamble, Martha Teke, Jeremy Fridling, Sarah G. Samaranayake, Bernadette Redd, Andrew Blakely, Jeremy L. Davis. Surveillance breast magnetic resonance findings in asymptomatic CDH1 variant carriers [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-03-23.