Postmenopausal mammographic breast density and subsequent breast cancer risk according to selected tissue markers.
BACKGROUND
This study aimed to determine if associations of pre-diagnostic percent breast density, absolute dense area, and non-dense area with subsequent breast cancer risk differ by the tumour's molecular marker status.


METHODS
We included 1010 postmenopausal women with breast cancer and 2077 matched controls from the Nurses' Health Study (NHS) and the Nurses' Health Study II (NHS II) cohorts. Breast density was estimated from digitised film mammograms using computer-assisted thresholding techniques. Information on breast cancer risk factors was obtained prospectively from biennial questionnaires. Polychotomous logistic regression was used to assess associations of breast density measures with tumour subtypes by the status of selected tissue markers. All tests of statistical significance were two sided.


RESULTS
The association of percent density with breast cancer risk appeared to be stronger in ER- as compared with ER+ tumours, but the difference did not reach statistical significance (density ⩾50% vs <10% odds ratio (OR)=3.06, 95% confidence interval (CI) 2.17-4.32 for ER+; OR=4.61, 95% CI 2.36-9.03 for ER-, Pheterogeneity=0.08). Stronger positive associations were found for absolute dense area and CK5/6- and EGFR- as compared with respective marker-positive tumours (Pheterogeneity=0.002 and 0.001, respectively). Stronger inverse associations of non-dense area with breast cancer risk were found for ER- as compared with ER+ tumours (Pheterogeneity=0.0001) and for AR+, CK5/6+, and EGFR+ as compared with respective marker-negative tumours (Pheterogeneity=0.03, 0.005, and 0.009, respectively). The associations of density measures with breast cancer did not differ by progesterone receptor and human epidermal growth factor receptor 2 status.


CONCLUSIONS
Breast density influences the risk of breast cancer subtypes by potentially different mechanisms.
Department of Epidemiology, College of Public Health and Health Professions and College of Medicine, University of Florida, 2004 Mowry Road, Gainesville, FL 32610, USA.
Lusine
L
Yaghjyan
Department of Epidemiology, Harvard School of Public Health, 181 Longwood Avenue, Boston, MA 02115, USA.|Department of Medicine Solna, Clinical Epidemiology Unit, Karolinska Institutet, 171 76 Solna, Stockholm, Sweden.
Andreas
A
Pettersson
Division of Public Health Sciences, Department of Surgery, Washington University in St Louis School of Medicine, 660S. Euclid Avenue, St Louis, MO 63110, USA.|Institute for Public Health, Washington University in St Louis, St Louis, MO, USA.
Graham A
GA
Colditz
Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.
Laura C
LC
Collins
Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.
Stuart J
SJ
Schnitt
Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.
Andrew H
AH
Beck
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA.
Bernard
B
Rosner
Department of Health Sciences Research, Mayo Clinic College of Medicine, Charlton 6-239, 200 First Street Southwest, Rochester, MN 55905, USA.
Celine
C
Vachon
Department of Epidemiology, Harvard School of Public Health, 181 Longwood Avenue, Boston, MA 02115, USA.|Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA.
Rulla M
RM
Tamimi
D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism*; D000071060:Breast Density; D001943:Breast Neoplasms / Q000150:complications / Q000209:etiology* / Q000378:metabolism; D016022:Case-Control Studies; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D042361:Mammary Glands, Human / Q000002:abnormalities* / Q000378:metabolism; D008875:Middle Aged; D017698:Postmenopause; D011446:Prospective Studies; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012307:Risk Factors
D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C512478:EGFR protein, human; D066246:ErbB Receptors