Hormonal Markers in Breast Cancer: Coexpression, Relationship with Pathologic Characteristics, and Risk Factor Associations in a Population-Based Study

Abstract

The objective of this study was to evaluate the coexpression patterns of hormonal markers in breast cancer tissue and their relationship with pathologic characteristics and epidemiologic risk factors. We evaluated the expression of 17 markers by immunohistochemistry in 842 invasive breast carcinomas collected in a population-based case-control study conducted in Poland. Based on marker correlations, factor analysis identified four major coexpression patterns ( factors): ''nuclear receptor factor'' [estrogen receptor (ER)-A, progesterone receptor, androgen receptor, cyclin D1, and aromatase], ''estrogen metabolism/ER-B factor'' (ER-B, peroxisome proliferator-activated receptor-;, steroid sulfatase, estrogen sulfonotransferase, and cytochrome P450 1B1), ''HER2 factor'' (human epidermal growth factor receptor 2, E-cadherin, cyclooxygenase-2, aromatase, steroid sulfatase), and ''proliferation factor'' (cytokeratin 5, cytokeratin 5/6, epidermal growth factor receptor, P53). Three of these factors corresponded to molecular subtypes previously defined by expression profiling; however, the estrogen metabolism/ER-B factor seemed to be distinctive. High scores for this factor were associated with high tumor grade (P heterogeneity = 0.02), younger age at menarche (P heterogeneity = 0.04), lower current body mass index among premenopausal women (P heterogeneity = 0.01), and older age at menopause (P heterogeneity = 0.04). High scores for the proliferation factor were also associated with early menarche (P heterogeneity < 0.0001), and in contrast to the estrogen metabolism/ ER-B factor, higher current body mass index among premenopausal women (P heterogeneity = 0.03). Our analysis of hormonal pathway markers independently confirmed several previously defined molecular subtypes identified by gene expression profiling and augmented these findings by suggesting the existence of additional relationships related to ER-B and enzymes involved in hormone metabolism. [Cancer Res 2007;67(21):10608-17]

CYP1B1 Is Not a Major Determinant of the Disposition of Aromatase Inhibitors in Epithelial Cells of Invasive Ductal Carcinoma

“…It should be noted that the number of cases of IDC evaluated in this study was small (n ϭ 29). A recent paper in a population based study (n ϭ 698) on hormonal markers in breast cancer identified a significant correlation ( p Ͻ 0.01, Pearson correlation coefficient ϭ 0.14) between CYP19 and CYP1B1 (Yang et al, 2007). We believe that the likely reason for the difference in results between this study and ours is sample size, with the larger study (Yang et al, 2007) having greater power to detect this correlation.…”

“…A recent paper in a population based study (n ϭ 698) on hormonal markers in breast cancer identified a significant correlation ( p Ͻ 0.01, Pearson correlation coefficient ϭ 0.14) between CYP19 and CYP1B1 (Yang et al, 2007). We believe that the likely reason for the difference in results between this study and ours is sample size, with the larger study (Yang et al, 2007) having greater power to detect this correlation. In another study (Esteban et al, 1992), a significant ( p ϭ 0.04), but inverse correlation between CYP19 and ER immunoreactivity was reported, indicating a likelihood of detecting CYP19 in ER-negative tumors.…”

Triple-Negative Breast Cancer: Risk Factors to Potential Targets

“…Although none of the older epidemiologic studies were designed to identify risk factors by molecular subtype, recent post hoc reanalyses also raise interesting questions about traditional risk factors and whether some risk factors are stronger for one subtype versus another or even have opposite effects in different subtypes. For example, in contradistinction to luminal breast cancer, higher parity and young age at first birth may be risk factors for basal-like breast cancer, whereas lack of breast feeding and early age of menarche may be stronger risk factors than for luminal breast cancers (41,43,44). Given our understanding of breast cancer as a heterogeneous disease, further research will need to focus on examination of individual risk factors within subtypes.…”

Expression and Clinical Significance of Insulin-Like Growth Factor 1 in Lung Cancer Tissues and Perioperative Circulation from Patients with Non-Small-Cell Lung Cancer

“…In each field, 200 cancer cells were counted (10,000 cells total), and the proportion of positive cells was calculated. Semi-quantitation was performed as previously reported 16 . In brief, quantitation was based on the staining intensity and the proportion of positive cells.…”