Associations of mammographic breast density with breast stem cell marker-defined breast cancer subtypes
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High mammographic breast density is a strong, well-established breast cancer risk factor. Whether stem cells may explain high breast cancer risk in dense breasts is unknown. We investigated the association between breast density and breast cancer risk by the status of stem cell markers CD44, CD24, and ALDH1A1 in the tumor.
We included 223 women with primary invasive or in situ breast cancer and 399 age-matched controls from Mayo Clinic Mammography Study. Percent breast density (PD), absolute dense area (DA), and non-dense area (NDA) were assessed using computer-assisted thresholding technique. Immunohistochemical analysis of the markers was performed on tumor tissue microarrays according to a standard protocol. We used polytomous logistic regression to quantify the associations of breast density measures with breast cancer risk across marker-defined tumor subtypes.
Of the 223 cancers in the study, 182 were positive for CD44, 83 for CD24 and 52 for ALDH1A1. Associations of PD were not significantly different across t marker-defined subtypes (51% + vs. 11–25%: OR 2.83, 95% CI 1.49–5.37 for CD44+ vs. OR 1.87, 95% CI 0.47–7.51 for CD44−, p-heterogeneity = 0.66; OR 2.80, 95% CI 1.27–6.18 for CD24+ vs. OR 2.44, 95% CI 1.14–5.22 for CD24−, p-heterogeneity = 0.61; OR 3.04, 95% CI 1.14–8.10 for ALDH1A1+ vs. OR 2.57. 95% CI 1.30–5.08 for ALDH1A1−, p-heterogeneity = 0.94). Positive associations of DA and inverse associations of NDA with breast cancer risk were similar across marker-defined subtypes.
We found no evidence of differential associations of breast density with breast cancer risk by the status of stem cell markers. Further studies in larger study populations are warranted to confirm these associations.
KeywordsMammographic breast density Breast cancer risk Breast stem cell markers CD44 CD24 ALDH1A1
This study was funded by the University of Florida Cancer Center through the Florida Consortium of National Cancer Institute Centers Program at the University of Florida (Bridge Funding to L.Y.); and Mayo Clinic Breast SPORE (NCI P50 CA116201) and National Cancer Institute (R01 CA128931; R01 CA140286). The authors would like to thank Ms. Elaine Dooley for performing immunohistochemical analyses for this study.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Research involving human participants and/or animals
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
This study was compliant with the U.S. Health Insurance Portability and Accountability Act and was approved by the Mayo Clinic Institutional Review Board (IRB) which issued a waiver of informed consent as well as the University of Florida IRBs. The Mayo Clinic patients provided a general authorization for use of medical record information for research purposes.
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