Differences in Risk Factors for Breast Cancer Molecular Subtypes in a Population-Based Study

• Published in: Cancer epidemiology, biomarkers & prevention Vol. 16; no. 3; pp. 439 - 443
• Main Authors: YANG, Xiaohong R, SHERMAN, Mark E, ZATONSKI, Witold, CARTUN, Richard, MANDICH, Daniza, RYMKIEWICZ, Grzegorz, LIGAJ, Marcin, LUKASZEK, Stanislaw, KORDEK, Radzisaw, GARCIA-CLOSAS, Montserrat, RIMM, David L, LISSOWSKA, Jolanta, BRINTON, Louise A, PEPLONSKA, Beata, HEWITT, Stephen M, ANDERSON, William F, SZESZENIA -DABROWSKA, Neonila, BARDIN-MIKOLAJCZAK, Alicja
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01-03-2007
• Subjects: Adult; Aged; Biological and medical sciences; breast cancer; Breast Neoplasms - classification; Breast Neoplasms - epidemiology; Female; Gynecology. Andrology. Obstetrics; Humans; Mammary gland diseases; Medical sciences; Middle Aged; Models, Statistical; molecular subtype; Neoplasm Invasiveness; Poland - epidemiology; Population Surveillance; population-based study; Prognosis; risk factor; Risk Factors; tissue microarray (TMA); Tumors; Poland; Human; erbB2 Gene; Breast cancer; Malignant tumor; Case control study; Gene expression; Epidemiology; Human Epidermal growth factor Receptor 2; Mammary gland diseases; Cancerology; C-Onc gene; Risk factor; Genetics; Public health; Comparative study; Protooncogene
• ISSN: 1055-9965; 1538-7755
• DOI: 10.1158/1055-9965.EPI-06-0806

Analysis of gene expression data suggests that breast cancers are divisible into molecular subtypes which have distinct clinical
features. This study evaluates whether pathologic features and etiologic associations differ among molecular subtypes. We
evaluated 804 women with invasive breast cancers and 2,502 controls participating in a Polish Breast Cancer Study. Immunohistochemical
stains for estrogen receptor α, progesterone receptor, human epidermal growth factor receptors (HER2 and HER1), and cytokeratin
5 were used to classify cases into five molecular subtypes: luminal A, luminal B, HER2-expresing, basal-like, and unclassified.
Relative risks were estimated using adjusted odds ratios and 95% confidence intervals. We observed that compared with the
predominant luminal A tumors (69%), other subtypes were associated with unfavorable clinical features at diagnosis, especially
HER2-expressing (8%) and basal-like (12%) tumors. Increasing body mass index significantly reduced the risk of luminal A tumors
among premenopausal women (odds ratios, 0.71; 95% confidence intervals, 0.57-0.88 per five-unit increase), whereas it did
not reduce risk for basal-like tumors (1.18; 0.86-1.64; P heterogeneity = 0.003). On the other hand, reduced risk associated with increasing age at menarche was stronger for basal-like (0.78; 0.68-0.89
per 2-year increase) than luminal A tumors (0.90; 0.95-1.08; P heterogeneity = 0.0009). Although family history increased risk for all subtypes (except for unclassified tumors), the magnitude of the
relative risk was highest for basal-like tumors. Results from this study have shown that breast cancer risk factors may vary
by molecular subtypes identified in expression studies, suggesting etiologic, in addition to clinical, heterogeneity of breast
cancer. (Cancer Epidemiol Biomarkers Prev 2007;16(3):439–43)