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- BRCA1/2 (1)
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Background
BRCA1 and, more commonly, BRCA2 mutations are associated with increased risk of male breast cancer (MBC). However, only a paucity of data exists on the pathology of breast cancers (BCs) in men with BRCA1/2 mutations. Using the largest available dataset, we determined whether MBCs arising in BRCA1/2 mutation carriers display specific pathologic features and whether these features differ from those of BRCA1/2 female BCs (FBCs).
Methods
We characterised the pathologic features of 419 BRCA1/2 MBCs and, using logistic regression analysis, contrasted those with data from 9675 BRCA1/2 FBCs and with population-based data from 6351 MBCs in the Surveillance, Epidemiology, and End Results (SEER) database.
Results
Among BRCA2 MBCs, grade significantly decreased with increasing age at diagnosis (P = 0.005). Compared with BRCA2 FBCs, BRCA2 MBCs were of significantly higher stage (P for trend = 2 × 10−5) and higher grade (P for trend = 0.005) and were more likely to be oestrogen receptor–positive [odds ratio (OR) 10.59; 95 % confidence interval (CI) 5.15–21.80] and progesterone receptor–positive (OR 5.04; 95 % CI 3.17–8.04). With the exception of grade, similar patterns of associations emerged when we compared BRCA1 MBCs and FBCs. BRCA2 MBCs also presented with higher grade than MBCs from the SEER database (P for trend = 4 × 10−12).
Conclusions
On the basis of the largest series analysed to date, our results show that BRCA1/2 MBCs display distinct pathologic characteristics compared with BRCA1/2 FBCs, and we identified a specific BRCA2-associated MBC phenotype characterised by a variable suggesting greater biological aggressiveness (i.e., high histologic grade). These findings could lead to the development of gender-specific risk prediction models and guide clinical strategies appropriate for MBC management.
We show that the topological Kitaev spin liquid on the honeycomb lattice is extremely fragile against the second-neighbor Kitaev coupling K\(_2\), which has recently been shown to be the dominant perturbation away from the nearest-neighbor model in iridate Na\(_2\)IrO\(_3\), and may also play a role in \(\alpha\)-RuCl\(_3\) and Li\(_2\)IrO\(_3\). This coupling naturally explains the zigzag ordering (without introducing unrealistically large longer-range Heisenberg exchange terms) and the special entanglement between real and spin space observed recently in Na\(_2\)IrO\(_3\). Moreover, the minimal K\(_1\) - K\(_2\) model that we present here holds the unique property that the classical and quantum phase diagrams and their respective order-by-disorder mechanisms are qualitatively different due to the fundamentally different symmetries of the classical and quantum counterparts.