Our speculation is that, in more aggressive BC samples, an alteration in polyamine metabolism alters the level of expression of hsa-let-7c, which in turn regulates the pluripotency capacity of the cancer stem cell population.
Based on the observation that frequent genomic alterations underlie a more aggressive cancer phenotype, we asked if such an effect could be detectable as an increase in the randomness of local gene expression patterns.
This apparently selective effect of EGFR polymorphisms might be due to the lower genomic instability of luminal A tumors in relation to other subtypes, which present more aggressive phenotypes due to superposed molecular alterations [ 43].
Tobacco might induce additional genetic alterations leading to a more aggressive phenotype.
The assumption of a constant population size may describe pre-malignant tissues in which genetic and epigenetic alterations lead to diversity before more aggressive clones arise.
Combinations of genetic alterations making an individual tumour more aggressive are highly likely to vary from case to case, depending upon histology, aetiology and other factors.
Molecular biological research has revealed that alcohol and its metabolites trigger many genetic and epigenetic alterations, 35, 36) leading to more aggressive biological behavior, cancer progression, and alcohol-associated reduced immune surveillance.
An alternative hypothesis is that the processes of breast involution that occurs following delivery, similar to wound healing where angiogenesis, inflammation and extracellular matrix alterations are activated, results in more aggressive breast cancer biology [ 48].
The HER2 gene is amplified in 15-20% of breast cancers and this molecular alteration carries with it a more aggressive clinical course [ 2- 4].
We here asked whether the presence of tumor necrosis, as a morphologic marker of tissue hypoxia [ 39], was associated with alterations in cell adhesion molecules and more aggressive melanoma features.
