Mammographic density and molecular subtypes of breast cancer

Background:Gene expression profiling has led to a subclassification of breast cancers independent of established clinical parameters, such as the Sorlie–Perou subtypes. Mammographic density (MD) is one of the strongest risk factors for breast cancer, but it is unknown if MD is associated with molecular subtypes of this carcinoma.Methods:We investigated whether MD was associated with breast cancer subtypes in 110 women with breast cancer, operated in Stockholm, Sweden, during 1994 to 1996. Subtypes were defined using expression data from HGU133A+B chips. The MD of the unaffected breast was measured using the Cumulus software. We used multinomial logistic models to investigate the relationship between MD and Sorlie–Perou subtypes.Results:Although the distribution of molecular subtypes differed in women with high vs low MD, this was statistically non-significant (P=0.249), and further analyses revealed no association between the MD and Sorlie–Perou subtypes as a whole, nor with individual subtypes.Conclusion:These findings suggest that although MD is one of the strongest risk factors for breast cancer, it does not seem to be differentially associated with breast cancer molecular subtypes. However, larger studies with more comprehensive covariate information are needed to confirm these results.

[1]  N. Boyd,et al.  Automated analysis of mammographic densities. , 1996, Physics in medicine and biology.

[2]  Therese Sørlie,et al.  Molecular classification of breast tumors: toward improved diagnostics and treatments. , 2007, Methods in molecular biology.

[3]  W. Willett,et al.  Plasma insulin-like growth factor (IGF) I, IGF-binding protein 3, and mammographic density. , 2000, Cancer research.

[4]  J. Thijssen Local biosynthesis and metabolism of oestrogens in the human breast. , 2004, Maturitas.

[5]  L. Bernstein,et al.  Is There a Difference in the Association between Percent Mammographic Density and Subtypes of Breast Cancer? Luminal A and Triple-Negative Breast Cancer , 2009, Cancer Epidemiology Biomarkers & Prevention.

[6]  Jack Cuzick,et al.  Determinants of percentage and area measures of mammographic density. , 2009, American journal of epidemiology.

[7]  N. Boyd,et al.  Mammographic density, response to hormones, and breast cancer risk. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[8]  K. Kerlikowske,et al.  Breast density, body mass index, and risk of tumor marker-defined subtypes of breast cancer. , 2012, Annals of epidemiology.

[9]  Monica Morrow,et al.  Impact of Breast Density on the Presenting Features of Malignancy , 2010, Annals of Surgical Oncology.

[10]  N F Boyd,et al.  Symmetry of projection in the quantitative analysis of mammographic images , 1996, European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation.

[11]  L. Holmberg,et al.  Gene expression profiling spares early breast cancer patients from adjuvant therapy: derived and validated in two population-based cohorts , 2005, Breast Cancer Research.

[12]  K. Kerlikowske,et al.  Effect of age, breast density, and family history on the sensitivity of first screening mammography. , 1996, JAMA.

[13]  V. McCormack,et al.  Breast Density and Parenchymal Patterns as Markers of Breast Cancer Risk: A Meta-analysis , 2006, Cancer Epidemiology Biomarkers & Prevention.

[14]  R. Tibshirani,et al.  Repeated observation of breast tumor subtypes in independent gene expression data sets , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[15]  Martin Yaffe,et al.  Mammographic density , 2009, Breast Cancer Research.

[16]  Joshy George,et al.  Genetic reclassification of histologic grade delineates new clinical subtypes of breast cancer. , 2006, Cancer research.

[17]  D. Grobbee,et al.  Measurements of Breast Density: No Ratio for a Ratio , 2005, Cancer Epidemiology Biomarkers & Prevention.

[18]  Anne M Kavanagh,et al.  Hormone replacement therapy and accuracy of mammographic screening , 2000, The Lancet.

[19]  L. Tabár,et al.  Effect of Baseline Breast Density on Breast Cancer Incidence, Stage, Mortality, and Screening Parameters: 25-Year Follow-up of a Swedish Mammographic Screening , 2010, Cancer Epidemiology, Biomarkers & Prevention.

[20]  Christian A. Rees,et al.  Molecular portraits of human breast tumours , 2000, Nature.

[21]  T. Sellers,et al.  Mammographic density, breast cancer risk and risk prediction , 2007, Breast Cancer Research.

[22]  N. Boyd,et al.  Mammographic density and breast cancer risk: current understanding and future prospects , 2011, Breast Cancer Research.

[23]  P. Hall,et al.  An expression signature for p53 status in human breast cancer predicts mutation status, transcriptional effects, and patient survival. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[24]  R. Tibshirani,et al.  Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[25]  N Harbeck,et al.  Triple-negative breast cancer--current status and future directions. , 2009, Annals of oncology : official journal of the European Society for Medical Oncology.

[26]  Stephen W Duffy,et al.  Using mammographic density to predict breast cancer risk: dense area or percentage dense area , 2010, Breast Cancer Research.

[27]  Philip M. Long,et al.  Breast cancer classification and prognosis based on gene expression profiles from a population-based study , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[28]  Yudi Pawitan,et al.  Intrinsic molecular signature of breast cancer in a population-based cohort of 412 patients , 2006, Breast Cancer Research.

[29]  M. Lux,et al.  Association of mammographic density with hormone receptors in invasive breast cancers: Results from a case‐only study , 2012, International journal of cancer.

[30]  Carla H van Gils,et al.  Mammographic density and breast cancer risk: the role of the fat surrounding the fibroglandular tissue , 2011, Breast Cancer Research.

[31]  P. Peeters,et al.  The epidemiological profile of women with an interval cancer in the DOM screening programme , 2004, Breast Cancer Research and Treatment.

[32]  Bernard Rosner,et al.  Mammographic breast density and subsequent risk of breast cancer in postmenopausal women according to tumor characteristics. , 2011, Journal of the National Cancer Institute.

[33]  G. Maskarinec,et al.  Comparison of mammographic densities and their determinants in women from Japan and Hawaii , 2002, International journal of cancer.

[34]  W. Foulkes,et al.  A Basal Epithelial Phenotype Is More Frequent in Interval Breast Cancers Compared with Screen Detected Tumors , 2005, Cancer Epidemiology Biomarkers & Prevention.

[35]  N. Boyd,et al.  Mammographic density and the risk and detection of breast cancer. , 2007, The New England journal of medicine.