TY - JOUR
T1 - Mammary collagen architecture and its association with mammographic density and lesion severity among women undergoing image-guided breast biopsy
AU - Bodelon, Clara
AU - Mullooly, Maeve
AU - Pfeiffer, Ruth M.
AU - Fan, Shaoqi
AU - Abubakar, Mustapha
AU - Lenz, Petra
AU - Vacek, Pamela M.
AU - Weaver, Donald L.
AU - Herschorn, Sally D.
AU - Johnson, Jason M.
AU - Sprague, Brian L.
AU - Hewitt, Stephen
AU - Shepherd, John
AU - Malkov, Serghei
AU - Keely, Patricia J.
AU - Eliceiri, Kevin W.
AU - Sherman, Mark E.
AU - Conklin, Matthew W.
AU - Gierach, Gretchen L.
N1 - Funding Information:
Open Access funding provided by the National Institutes of Health (NIH). This study was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics of the National Cancer Institute and National Cancer Institute federal funds awarded under Contract No. HHSN261200800001E to SAIC-Frederick, Inc. Breast Cancer Research Stamp Funds and cooperative agreement U01CA70013 (P. Vacek, D. Weaver) and 1R21CA157254 (J. Shepherd, A. Mahmoudzadeh) and RO1 CA199996 (M. Conklin, P. Keely, K. Eliceiri) from the National Cancer Institute funded some of the data collection and image analysis for this study. Grant Number M01 RR000109 from the National Center for Research Resources funded the blood processing at the University of Vermont’s General Clinical Research Center. The efforts of Drs. Sprague, Vacek, and Weaver were supported in part by cooperative agreement U01CA196383 and U54CA163303 from the National Cancer Institute. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - Background: Elevated mammographic breast density is a strong breast cancer risk factor with poorly understood etiology. Increased deposition of collagen, one of the main fibrous proteins present in breast stroma, has been associated with increased mammographic density. Collagen fiber architecture has been linked to poor outcomes in breast cancer. However, relationships of quantitative collagen fiber features assessed in diagnostic biopsies with mammographic density and lesion severity are not well-established. Methods: Clinically indicated breast biopsies from 65 in situ or invasive breast cancer cases and 73 frequency matched-controls with a benign biopsy result were used to measure collagen fiber features (length, straightness, width, alignment, orientation and density (fibers/µm2)) using second harmonic generation microscopy in up to three regions of interest (ROIs) per biopsy: normal, benign breast disease, and cancer. Local and global mammographic density volumes were quantified in the ipsilateral breast in pre-biopsy full-field digital mammograms. Associations of fibrillar collagen features with mammographic density and severity of biopsy diagnosis were evaluated using generalized estimating equation models with an independent correlation structure to account for multiple ROIs within each biopsy section. Results: Collagen fiber density was positively associated with the proportion of stroma on the biopsy slide (p < 0.001) and with local percent mammographic density volume at both the biopsy target (p = 0.035) and within a 2 mm perilesional ring (p = 0.02), but not with global mammographic density measures. As severity of the breast biopsy diagnosis increased at the ROI level, collagen fibers tended to be less dense, shorter, straighter, thinner, and more aligned with one another (p < 0.05). Conclusions: Collagen fiber density was positively associated with local, but not global, mammographic density, suggesting that collagen microarchitecture may not translate into macroscopic mammographic features. However, collagen fiber features may be markers of cancer risk and/or progression among women referred for biopsy based on abnormal breast imaging.
AB - Background: Elevated mammographic breast density is a strong breast cancer risk factor with poorly understood etiology. Increased deposition of collagen, one of the main fibrous proteins present in breast stroma, has been associated with increased mammographic density. Collagen fiber architecture has been linked to poor outcomes in breast cancer. However, relationships of quantitative collagen fiber features assessed in diagnostic biopsies with mammographic density and lesion severity are not well-established. Methods: Clinically indicated breast biopsies from 65 in situ or invasive breast cancer cases and 73 frequency matched-controls with a benign biopsy result were used to measure collagen fiber features (length, straightness, width, alignment, orientation and density (fibers/µm2)) using second harmonic generation microscopy in up to three regions of interest (ROIs) per biopsy: normal, benign breast disease, and cancer. Local and global mammographic density volumes were quantified in the ipsilateral breast in pre-biopsy full-field digital mammograms. Associations of fibrillar collagen features with mammographic density and severity of biopsy diagnosis were evaluated using generalized estimating equation models with an independent correlation structure to account for multiple ROIs within each biopsy section. Results: Collagen fiber density was positively associated with the proportion of stroma on the biopsy slide (p < 0.001) and with local percent mammographic density volume at both the biopsy target (p = 0.035) and within a 2 mm perilesional ring (p = 0.02), but not with global mammographic density measures. As severity of the breast biopsy diagnosis increased at the ROI level, collagen fibers tended to be less dense, shorter, straighter, thinner, and more aligned with one another (p < 0.05). Conclusions: Collagen fiber density was positively associated with local, but not global, mammographic density, suggesting that collagen microarchitecture may not translate into macroscopic mammographic features. However, collagen fiber features may be markers of cancer risk and/or progression among women referred for biopsy based on abnormal breast imaging.
KW - Breast diseases
KW - Breast neoplasms
KW - Breast pathology
KW - Collagen fibers
KW - Mammographic density
KW - Second harmonic generation imaging
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U2 - 10.1186/s13058-021-01482-z
DO - 10.1186/s13058-021-01482-z
M3 - Article
C2 - 34753492
AN - SCOPUS:85118778399
VL - 23
JO - Breast Cancer Research
JF - Breast Cancer Research
SN - 1465-5411
IS - 1
M1 - 105
ER -