Abstract P6-07-08: Androgen receptor (AR) mutations in a cohort of patients with breast cancer (BC) who have undergone tumor genomic profiling

Abstract

Abstract Background: AR mutations have been described as a mechanism of resistance to AR antagonists in prostate cancer. There are limited data regarding the presence of AR mutations in breast cancer. We aim to describe the presence of tumor AR mutations in a cohort of patients (pts) with breast cancer who are candidates for targeted cancer therapy, who underwent tumor genomic profiling as part of a clinical trial at MSK (NCT01775072). Methods: MSK-IMPACT is a targeted tumor sequencing assay capable of detecting mutations and other critical genetic aberrations in 410 cancer genes; these data are available through an institutional database. Following IRB approval and using an electronic medical record, we examined the subset of pts in this database with breast cancer for the presence of AR mutations and performed a chart review for clinicopathologic features and outcomes. Statistics are descriptive. Results: As of 03JUN2015, 628 of 4,379 samples that underwent MSK-IMPACT testing since 2012 were from invasive breast cancers. 6 of 628 (1%) harbored AR mutations (Table 1), none of which contribute to a reported or predicted functional alteration. Table 1MutationTypeAllele FrequencyFunctional Impact According to MutationAssessorR31HMissense0.21LowR856CMissense0.31MediumA430TMissense0.12NeutralG409RMissense0.18MediumQ445PMissense0.47MediumQ73LMissense0.25Neutral Patient/tumor characteristics are shown in Table 2. Five out of 6 patients recurred between 7.4 and 117.4 months (mo) from the date of initial diagnosis. One patient is without disease recurrence at 3.9mo from diagnosis at date of last contact, 7.9mo ago. Table 2MutationStage at DiagnosisHIstologyER%/PR%/HER2AR%Sites of MBCSite of IMPACTR31HT1N0Lobular90/20/1+-SkinSkinR856CT3N3Ductal20/0/1+0Chest wall, LNLNA430TT2N1Ductal95/0/--Bone, liverBreastG409RT2N0Ductal90/80/FISH 1.3-Bone, liverLiverQ445PT3N3Ductal99/50/1+-LNBreast/LNQ73LT3N0Malignant Phyllodes--N/ABreastMBC metastatic breast cancer; LN lymph node; N/A not applicable Conclusions: AR mutations were uncommon in this dataset of 628 breast cancers. Similarly, TCGA sequencing data has revealed only 12 invasive breast cancers with AR mutations (2.2% of 973 samples). The functional significance of these mutations has not been demonstrated. As tissue from therapeutic studies using AR antagonists for the treatment of breast cancer become available, mutations or amplification in AR may be more readily identified as a potential mechanism of resistance to AR-targeted therapy. Acknowledgments: We gratefully acknowledge the members of the Molecular Diagnostics Service in the Department of Pathology and the Marie-Josée and Henry R. Kravis Center for Molecular Oncology. Citation Format: Gucalp A, Proverbs-Singh TA, Razavi P, Chandarlapaty S, Patil S, Ross DS, Zehir A, Baselga J, Hudis CA, Traina TA. Androgen receptor (AR) mutations in a cohort of patients with breast cancer (BC) who have undergone tumor genomic profiling. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-07-08.