Male BC is usually ER, PR and AR-positive, Luminal B-like/HER2-negative. Of note, 56% patients had T1 tumors but only 4% had BCS. ER was highly positive in >90% of cases but only 77% received adjuvant ET. ER, PR and AR were associated with OS and RFS, whereas grade, Ki67 and IHC surrogates were not. Significant improvement in survival over time was observed.

Phyllodes tumours (PTs) are breast fibroepithelial lesions that are graded based on histological criteria as benign, borderline or malignant. PTs may recur locally. Borderline PTs and malignant PTs may metastasize to distant sites. Breast fibroepithelial lesions, including PTs and fibroadenomas, are characterized by recurrent MED12 exon 2 somatic mutations. We sought to define the repertoire of somatic genetic alterations in PTs and whether these may assist in the differential diagnosis of these lesions. We collected 100 fibroadenomas, 40 benign PTs, 14 borderline PTs and 22 malignant PTs. Six, 6 and 13 benign, borderline and malignant PTs respectively and their matched normal tissue were subjected to targeted massively parallel sequencing (MPS) using the MSK-IMPACT sequencing assay. Recurrent MED12 mutations were found in 56% of PTs; in addition, mutations affecting cancer genes (e.g. TP53, RB1, SETD2 and EGFR) were exclusively detected in borderline and malignant PTs. We found a novel recurrent clonal hotspot mutation in the TERT promoter (−124 C>T) in 52% and TERT gene amplification in 4% of PTs. Laser capture microdissection revealed that these mutations were restricted to the mesenchymal component of PTs. Sequencing analysis of the entire cohort revealed that the frequency of TERT alterations increased from benign (18%), to borderline (57%) and to malignant PTs (68%; P<0.01), and TERT alterations were associated with increased levels of TERT mRNA (P<0.001). No TERT alterations were observed in fibroadenomas. An analysis of TERT promoter sequencing and gene amplification distinguished PTs from fibroadenomas with a sensitivity and a positive predictive value of 100% (CI 95.38%–100%) and 100% (CI 85.86%–100%), respectively, and a sensitivity and a negative predictive value of 39% (CI 28.65%–51.36%) and 68% (CI 60.21%–75.78%), respectively. Our results suggest that TERT alterations may drive the progression of PTs, and may assist in the differential diagnosis between PTs and fibroadenomas.

There is a need to image excised tissues during tumor-resection procedures in order to identify residual tumors at the margins and to guide their complete removal. The imaging of dysregulated cell-surface receptors is a potential means of identifying the presence of diseases with high sensitivity and specificity. However, due to heterogeneities in the expression of protein biomarkers in tumors, molecular-imaging technologies should ideally be capable of visualizing a multiplexed panel of cancer biomarkers. Here, we demonstrate that the topical application and quantification of a multiplexed cocktail of receptor-targeted surface-enhanced Raman scattering (SERS) nanoparticles (NPs) enables rapid quantitative molecular phenotyping (QMP) of the surface of freshly excised tissues to determine the presence of disease. In order to mitigate the ambiguity due to nonspecific sources of contrast such as off-target binding or uneven delivery, a ratiometric method is employed to quantify the specific vs. nonspecific binding of the multiplexed NPs. Validation experiments with human tumor cell lines, fresh human tumor xenografts in mice, and fresh human breast specimens demonstrate that QMP imaging of excised tissues agrees with flow cytometry and immunohistochemistry, and that this technique may be achieved in less than 15 minutes for potential intraoperative use in guiding breast-conserving surgeries.

Purpose Male breast cancer (MaBC) is rare and its genomic landscape has yet to be fully characterized. Lacking studies in men, treatment of MaBC patients is extrapolated from results in females with the disease (FBC). We sought to define whether MaBCs harbor somatic genetic alterations in genes frequently altered in FBCs. Experimental Design All MaBCs were estrogen receptor-positive and all but two were HER2 negative. 59 MaBCs were subtyped by immunohistochemistry and tumor-normal pairs were microdissected and subjected to massively parallel sequencing targeting all exons of 241 genes frequently mutated in FBCs or DNA-repair related. The repertoires of somatic mutations and copy number alterations of MaBCs were compared to that of subtype-matched FBCs. Results 29% and 71% of MaBCs were immunohistochemically classified as luminal A-like or luminal B-like, respectively. MaBCs displayed a heterogeneous repertoire of somatic genetic alterations that to some extent recapitulated that of estrogen receptor (ER)-positive/HER2-negative FBCs, including recurrent mutations affecting PIK3CA (20%) and GATA3 (15%). ER-positive/HER2-negative MaBCs, however, less frequently harbored 16q losses, and PIK3CA and TP53 mutations than ER-positive/HER2-negative FBCs. In addition, MaBCs were found to be significantly enriched for mutations affecting DNA repair-related genes. Conclusion MaBCs less frequently harbor somatic genetic alterations typical of ER-positive/HER2-negative FBCs, such as PIK3CA and TP53 mutations and losses of 16q, suggesting that at least a subset of MaBCs are driven by a distinct repertoire of somatic changes. Given the genomic differences, caution may be needed in the application of biological and therapeutic findings from studies of FBCs to MaBCs.

Aims Somatic mutations in exon 2 of the MED12 gene have been identified in 60% of breast fibroadenomas (FAs). The aim of this study was to define whether phyllodes tumors (PTs) would harbor MED12 somatic mutations in a way akin to FAs. Methods and results A collection of 73 fibroepithelial tumors (including 26 FAs, 25 benign PTs, 9 borderline PTs and 13 malignant PTs) from 64 patients was retrieved from the authors' institution. Sections from FFPE blocks were microdissected to ensure an enrichment in neoplastic stromal elements of >70%. DNA samples extracted from tumor and matched normal tissues were subjected to Sanger sequencing of exon 2 of the MED12 gene. MED12 exon 2 somatic mutations, including 28 somatic single nucleotide variants and 19 insertions and deletions, were found in 65%, 88%, 78% and 8% of FAs, benign PTs, borderline PTs and malignant PTs, respectively. Malignant PTs significantly less frequently harbored MED12 exon 2 somatic mutations than FAs, benign and borderline PTs. Conclusions Although MED12 exon 2 somatic mutations likely constitute the driver genetic event of most FAs, benign and borderline PTs, our results suggest that the majority of malignant PTs may be driven by other genetic/epigenetic alterations.