In a case-controls study of 579 women with primary incident breast cancer and 574 controls matched on age and time of blood collection, we examined serum concentrations of 25OHD at diagnosis or enrollment, with a particular focus on associations with breast cancer prognostic characteristics, specifically, tumor histologic grade, ER status, and molecular subtypes characterized by ER, PR and HER2.
For example, ER + tumors generally fall into the luminal A and B molecular subtypes, characterized by expression of the ER as well as cytokeratins typically expressed by luminal epithelial cells [ 1, 3].
Renal cell carcinomas (RCCs) with Xp11 translocation (Xp11 RCC) constitute a distinctive molecular subtype characterized by chromosomal translocations involving the Xp11.2 locus, resulting in gene fusions between the TFE3 transcription factor with a second gene (usually ASPSCR1, PRCC, NONO, or SFPQ).
When the molecular subtypes were characterized according to tumor characteristics, treatment and HRT use, quite a complex pattern emerged (Table 4).
To determine molecular subtypes we characterized over 200 tumor specimens obtained from Egypt by performing ER, PR, Her2, CK5/6, EGFR and Ki67 immunohistochemistry. Our study demonstrated that the Luminal A subtype, associated with favorable prognosis, was found in nearly 45% of cases examined.
The subtypes characterized by molecular genetic typing methods provide a greater power and ability to differentiate strains than previous methods, such as comparisons of patterns of drug resistance or phage-typing (4, 5).
Evidence is accumulating to suggest that breast cancer is a collection of biologically distinct disease subtypes characterized by unique gene expression profiles, molecular or protein markers, and that exhibit variable clinical behavior, prognosis, and response to therapies [ 9, 10, 18- 21].
Breast cancer comprises many different subtypes characterized by distinguishing factors such as cell type of origin, grade and molecular specificities such as Ki-67 levels and receptor status.
Breast cancer can be classified according to molecular and histological subtypes with the most aggressive behavior usually being attributed to the triple negative (TN) subtypes, characterized with loss of estrogen, progesterone, and Her2 receptor expressions [ 1– 3].
Five molecular subtypes were identified, characterized by WNT signaling (A; 9 cases), SHH signaling (B; 15 cases), expression of neuronal differentiation genes (C and D; 16 and 11 cases, respectively) or photoreceptor genes (D and E; both 11 cases).
Over a decade ago, the first large-scale gene expression profiling studies in breast cancer demonstrated that breast cancers consist of a number of "intrinsic" or "molecular" subtypes that are characterized by similarities in gene expression patterns [ 6].
