Impact of early testing and analysis of germline genetic mutation patterns in patients with breast cancer: A single institution experience.

Abstract

10613 Background: Approximately 3% of patients with breast cancer have a pathogenic or likely pathogenic variant (mutation) in a high-risk breast cancer gene, such as BRCA1, BRCA2and PALB2, which increases breast cancer risk more than fourfold. Approximately 3% have a germline mutation in a moderate-penetrance breast cancer gene, such as ATM or CHEK2, which confers a two- to threefold increased risk of breast cancer. Methods: In 2020 we started offering germline genetic testing to all newly diagnosed breast cancer patients at the time of diagnosis irrespective of their family history. Our objectives included the following: Prevalence of mutations in breast cancer patients treated at our institution. Germline mutations in patients with Ductal carcinoma in situ (DCIS). To identify if early universal germline testing affected the surgical modality. Results: A total of 525 patients were seen in the oncology clinic from January 2020 to December 2022 with a breast cancer diagnosis. The median age of diagnosis is 66 (32-91) years. Invasive ductal cancer (IDC 66 %) was the most common subtype, followed by DCIS (18%) (Table 1). Most patients had estrogen-positive cancer (82% vs. 18%), and approximately 13% had HER2-positive disease (61% HER2 low). Mutation in CHEK2 (9 patients) was our cohort's most common pathogenic mutation, followed by BRCA1 (6 patients) and MUYTH (6 patients) genes. Predominant germline mutations were identified in patients with IDC, followed by DCIS. One patient with a pure mucinous subtype had a germline pathogenic mutation (RECQL4 gene). We identified a higher percentage of pathogenic breast cancer-related mutations in patients above 60 years (63% vs. 37%) and all CHEK2 mutations were in patients above 60. Out of 41 patients with pathogenic mutations, 17 underwent a partial mastectomy, 12 had a bilateral mastectomy, and two had a unilateral mastectomy. All patients with BRCA1/2 mutation chose bilateral mastectomy, and all patients with a CHEK2 mutation underwent a partial mastectomy. Several variants of unknown significance (VUS) mutations were identified, and they followed a similar pattern, being more common in patients with IDC. VUS mutations in the ATM gene were the most reported abnormality. Conclusions: Pathogenic mutation in the CHEK2 gene is more prevalent, and we hypothesize that this finding could be related to the demographic population treated in our institution. Also, CHEK2 mutation was only identified in patients older than 60, which argues for more testing in patients in this age group. Approximately 9% of all IDC patients had a germline mutation compared to 4.2 % in patients with DCIS. Our review identifies that patients with BRCA1/2 mutations tend to undergo prophylactic mastectomy, and early testing likely impacted this decision. From our study, we believe that germline genetic testing should be offered to all breast cancer patients.