Molecular determinants of post-mastectomy breast cancer recurrence.

摘要: Breast cancer (BC) adjuvant therapy after mastectomy in the setting of 1–3 positive lymph nodes has been controversial. This retrospective Translational Cancer Research Consortium study evaluated molecular aberrations primary cancers associated with locoregional recurrence (LRR) or distant metastasis (DM) compared to non-recurrent controls. We identified 115 HER2 negative, naive, T and N 0-1 BC patients treated but no post-mastectomy radiotherapy. included 32 LRR, 34 DM, 49 RNAseq was performed on tumors 110 patients; difference RNA profiles between DNA analysis 57 (17 15 25 controls) significantly more NF1 mutations mitogen-activated protein kinase (MAPK) pathway gene LRR (24%, 47%) DM (27%, 40%) controls (0%, 0%; p < 0.0001 p = 0.0070, respectively). Three had matched vs. samples, one patient a gain mutation LRR. There significant groups for PTEN loss cleaved caspase 3 expression. The mean percentage Ki 67 labeling index higher (29.2%) (26%) (14%, p = 0.0045). In summary, MAPK pathway, specifically NF1, were both suggesting that alterations signaling are aggressive tumor phenotype. Validation these associations tissues from randomized trials may support targeted reduce breast recurrence.