Characteristics and outcome of breast cancers diagnosed in patients with germline ATM mutations.

Abstract

10622 Background: The purpose of this study is to investigate clinicopathologic characteristics of invasive breast cancers diagnosed in individuals carrying germline mutations in ATM. Individuals with germline pathogenic variants (PV) in ATM have an elevated lifetime risk of breast cancer (17-52%). Clinical characteristics and outcomes of breast cancer amongst patients with ATM PV are not well described. Our aim was to describe a cohort and clinical outcome of patients with breast cancer and ATM PVs. Methods: Patients receiving care at MD Anderson Cancer Center with at least one invasive breast cancer diagnosis and who underwent germline testing and were found to have a germline ATM PV were included in the study. Individuals with co-occurring germline mutations in BRCA2 and CHEK2 were excluded. Germline positive and tested negative patients were identified using our prospective Breast Cancer and Clinical Cancer Genetics research database. Results: 86 patients with ATM PV were identified. Overall ER positivity was 94.19%. 72.09% were ER+/HER2- and 22.09% were ER+/HER2+. HER2+/ER- and TNBC occurred at lower rates in this cohort (2.33% each). When compared to ATM PV negative, patients with ATM PVs were more likely to have ER+ tumors (HR 1.26). Most individuals with ATM PVs were diagnosed with Stage I (40.7%) or II (34.9%) disease. However, they were more likely to be diagnosed at Stage IV than the control cohort (10.47% vs 1.99%, HR 5.25). Amongst patients receiving neoadjuvant chemotherapy, the pathologic Complete Response (pCR) rate in the ATM positive cohort was 15.63% (5/32), compared to 46.09% in the control group. Locoregional recurrence rates were similar in the ATM and control cohorts (8.14% and 5.85%), but those with germline ATM PVs were more likely to have distant recurrence (23.26% vs 10.96%, HR 2.12).Individuals with germline ATM PVs were also more likely to be diagnosed with a second or third invasive breast cancer than those in the control group (9.3% vs 2.79%, HR 3.33). Overall survival was not significantly different between the two cohorts. In addition to invasive breast cancers, we collected data on secondary malignancies and found that in the ATM PV cohort, 34.88% were diagnosed with at least one additional invasive cancer, including breast, gynecologic, colorectal, pancreatic, melanoma, and other tumor types. Conclusions: Patients with hereditary ATM PVs diagnosed with breast cancer have distinct characteristics and outcomes. In our cohort patients with ATM PVs had a higher risk of distant metastasis suggesting a more aggressive disease course that may require tailored treatment strategies. In addition, they also have an increased risk of developing second and third primary breast cancers, therefore risk reducing mastectomy should be considered. Finally, because of increased risk of non-breast malignancies, screening for potential new malignancies is warranted in this patient population.