Both ER + HER2+ breast cancer presents a heterogeneous biology, which is yet to be explored. Thus, using the cohort of our previous phase II study, we investigated their somatic mutation profile to find out the frequency and clinical implication.
Formalin-fixed paraffin-embedded (FFPE) tissue from 21 postmenopausal ER + HER2+ breast cancer patients were obtained from Asan Medical Center. The samples were sequenced by targeted capture sequencing with NGDx (coding sequence of 585 cancer-related genes + selected introns from 57 genes). Sequenced data were mapped to the reference human genome (hg19) using the Burrows-Wheeler Aligner, and were processed using publicly available Picard and the Genome Analysis Toolkit. Single nucleotide variant calls from MuTect were filtered against the dbSNP database to enrich for somatic mutations. Copy number alterations were detected by G + C normalization of read depth of coverage.
|Gene mutation||ER + HER2+ breast cancer in TCGA||Neo ALL- IN|
|AA change/frequency||AA change/frequency|
|Exon 9 (helical domain)||E542K: 11% E545K: 16% Q546K: 1% Q546P: |
Activating mutations in PIK3CA were abundantly found in postmenopausal ER + HER2+ breast cancer in our cohort. We carefully speculate that they might confer resistance to anti-HER-2 treatment combined with hormone therapy in neoadjuvant setting, and benefit of adding PI3K inhibitor should be considered in this subtype.
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All authors have declared no conflicts of interest.