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Key Clinical Message: A rare missense mutation was identified as a reversion mutation using cancer genomic profiling and a suspected mechanism underlying resistance to olaparib in breast cancer. A 34‐year‐old woman with breast cancer and BRCA2: p.Gln3047Ter was treated with olaparib. After tumor progression, cancer genomic profiling testing using liquid biopsy revealed BRCA2 p.Gln3047Ter and p.Gln3047Tyr, with 48.9% and 0.37% allele frequency, respectively. These findings shed light on reversion mutation as a mechanism of resistance to olaparib in breast cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer (BC) in adolescents and young adults (AYA) has unique biological qualities, but the details of these features remain unclear, and treatment options are comparable to those of other age groups. In this study, we identified a gene that demonstrates a strong association with patient prognosis solely in AYA patients, despite the fact that its expression does not differ by age group. Although this gene, GALNT1, has no prognostic significance in whole BC, when examined in AYA BC, high GALNT1 was significantly associated with worse survival. Furthermore, high GALNT1 expression was found to be an independent factor for survival among several clinical features of AYA patients. Finally, high GALNT1 BC is associated with increased EMT, angiogenesis, and protein secretion in AYA patients, but not in the elderly. We report the clinical relevance of the GALNT1 gene in AYA BC. It is well established that genetic information differs amongst the adolescent and young adult population (AYA) and older patients. Although several studies on genetic information have been conducted, no current prognostic biomarker exists to help differentiate survival outcomes amongst AYA patients. The GALNT family of genes have been associated with several cancer etiologies, such as the Tn antigen and epithelial-mesenchymal transition (EMT); however, the clinical significance of GALNT1 expression in breast cancer (BC) remains unclear. We investigated the clinical relevance of GALNT1 expression in BC using two large independent cohorts. We found that, although triple-negative BC (TNBC) had the highest GALNT1 expression compared to ER-positive/HER2-negative BC, GALNT1 levels in BC were not associated with clinical aggressiveness, including histological grade, AJCC stage and N-category, and patient survival, consistently in both the METABRIC and GSE96058 cohorts. There was also no biological difference between low- and high-GALNT1 expression BC, as analyzed by hallmark gene sets via gene set enrichment analysis (GSEA). Further, no significant difference was found in GALNT1 expression levels among AYAs and older patients. However, high GALNT1 expression was associated with significantly worse survival in AYA patients, in both cohorts. Furthermore, high GALNT1 expression was found to be an independent factor among several clinical features, including subtype, histological grade, AJCC T and N-category, in AYA patients. In both cohorts, BC with high GALNT1 expression demonstrated low levels of CD8+ T-cell infiltration, but not other anti-cancerous or pro-cancerous immune cells. Finally, high levels of GALNT1 BC demonstrated increased EMT, angiogenesis, and protein secretion in the AYA population, but not in older patients. In conclusion, our findings demonstrate that GALNT1 expression was found to be associated with angiogenesis and EMT, and may have potential as prognostic biomarker, specifically in AYA patients. [ABSTRACT FROM AUTHOR]

Sentinel lymph node (SLN) biopsy has been the standard modality for breast cancer patients with clinically node negative disease. In patients who undergo axillary lymph node dissection (ALND) due to SLN metastasis, the harvested nodes (non-SLNs) often contain no metastasis. Here, we evaluated the predictive factors associated with non-SLN metastasis in breast cancer patients. This was a retrospective study of patients with operable cT1-3, cN0 invasive breast cancer who underwent SLN biopsy followed by ALND due to SLN metastasis. The clinicopathologic factors and predictive factors of non-SLN metastasis were analyzed. The optimal cutoff for the Ki67 index and the number of positive and negative SLNs that were predictive of non-SLN metastasis were evaluated using receiver operating characteristic curves. The median number of SLN and non-SLN was 3 and 11, respectively. Of the 150 patients, 52 (35.0%) had metastases in non-SLNs. The optimal cutoffs for the Ki67 index and the number of positive and negative SLNs were of 12%, 2, and 1, respectively. In the univariate analysis, the Ki67 index and the number of positive SLNs≥2 and negative SLNs≤1 were higher in the non-SLN + group than that in the non-SLN – group. The number of negative SLNs was as a predictive factor for non-SLNs metastasis in the multivariate analysis. The number of negative SLNs predicts the risk of non-SLN metastasis in breast cancer. When deciding on whether to omit ALND, the number of positive and negative SLNs should be considered. [ABSTRACT FROM AUTHOR]