Mammary collagen architecture and its association with mammographic density and lesion severity among women undergoing image-guided breast biopsy

Bodelon, Clara; Mullooly, Maeve; Pfeiffer, Ruth M.; Fan, Shaoqi; Abubakar, Mustapha; Lenz, Petra; Vacek, Pamela M.; Weaver, Donald L.; Herschorn, Sally D.; Johnson, Jason M.; Sprague, Brian L.; Hewitt, Stephen; Shepherd, John; Malkov, Serghei; Keely, Patricia J.; Eliceiri, Kevin W.; Sherman, Mark E.; Conklin, Matthew W.; Gierach, Gretchen L.

doi:10.1186/s13058-021-01482-z

Table 1 Associations of collagen fiber characteristics with histologic tissue composition metrics and radiologic mammographic density measures among women undergoing diagnostic breast biopsy

From: Mammary collagen architecture and its association with mammographic density and lesion severity among women undergoing image-guided breast biopsy

	All subjects (138 women, 243 ROI) β (95% CI)	p Value	Controls (73 women, 133 ROI) β (95% CI)	p Value	Cases (65 women, 110 ROI) β (95% CI)	p Value
Tissue composition
Percent stroma on slide
Fiber characteristic
Average length (μm)	0.09 (− 0.14, 0.32)	0.462	0.15 (− 0.21, 0.50)	0.421	− 0.02 (− 0.29, 0.24)	0.869
Median straightness	− 0.14 (− 0.38, 0.10)	0.255	− 0.03 (− 0.43, 0.37)	0.875	− 0.24 (− 0.51, 0.03)	0.076
Average width (μm)	− 0.12 (− 0.37, 0.12)	0.323	− 0.15 (− 0.50, 0.20)	0.402	− 0.12 (− 0.41, 0.17)	0.403
Median alignment (in 44.91 μm × 44.91 μm)	0.07 (− 0.18, 0.32)	0.588	0.21 (− 0.18, 0.60)	0.297	− 0.12 (− 0.41, 0.16)	0.387
Density (number of fibers/100 μm²)	0.57 (0.31, 0.84)	2.0 × 10^–5	0.65 (0.33, 0.98)	7.9 × 10^–5	0.45 (0.05, 0.85)	0.027
Median orientation (°)	0.06 (− 0.25, 0.37)	0.717	− 0.14 (− 0.65, 0.38)	0.6	0.27 (− 0.07, 0.61)	0.124
Percent epithelium on slide
Fiber characteristic
Average length (μm)	− 0.17 (− 0.35, 0.02)	0.078	− 0.02 (− 0.23, 0.19)	0.867	− 0.35 (− 0.64, − 0.07)	0.016
Median straightness	− 0.25 (− 0.44, − 0.06)	0.012	− 0.06 (− 0.30, 0.18)	0.610	− 0.41 (− 0.68, − 0.13)	3.6 × 10^–3
Average width (μm)	− 0.14 (− 0.32, 0.04)	0.129	0.02 (− 0.17, 0.21)	0.855	− 0.4 (− 0.70, − 0.10)	9.6 × 10^–3
Median alignment (in 44.91 μm × 44.91 μm)	0.01 (− 0.15, 0.18)	0.885	0.06 (− 0.10, 0.22)	0.439	− 0.06 (− 0.38, 0.25)	0.692
Density (number of fibers/100 μm²)	− 0.12 (− 0.28, 0.04)	0.150	− 0.12 (− 0.30, 0.06)	0.193	− 0.14 (− 0.40, 0.13)	0.302
Median orientation (°)	0.17 (− 0.07, 0.4)	0.169	− 0.10 (− 0.32, 0.13)	0.392	0.41 (0.06, 0.75)	0.021
Percent fat on slide
Fiber characteristic
Average length (μm)	0.05 (− 0.23, 0.32)	0.745	− 0.11 (− 0.45, 0.23)	0.537	0.22 (− 0.21, 0.66)	0.309
Median straightness	0.32 (0.02, 0.61)	0.034	0.09 (− 0.30, 0.49)	0.645	0.51 (0.10, 0.91)	0.014
Average width (μm)	0.14 (− 0.15, 0.42)	0.352	0.06 (− 0.30, 0.41)	0.755	0.27 (− 0.19, 0.74)	0.249
Median alignment (in 44.91 μm × 44.91 μm)	− 0.03 (− 0.32, 0.25)	0.815	− 0.2 (− 0.59, 0.19)	0.318	0.18 (− 0.25, 0.60)	0.416
Density (number of fibers/100 μm²)	− 0.49 (− 0.76, − 0.21)	6.6 × 10^–4	− 0.49 (− 0.80, − 0.18)	2.1 × 10^–3	− 0.45 (− 0.92, 0.02)	0.059
Median orientation (°)	− 0.23 (− 0.56, 0.10)	0.167	0.09 (− 0.38, 0.55)	0.708	− 0.53 (− 0.94, − 0.12)	0.011
MD measures
Global mammographic density
% FGV
Fiber characteristic
Average length (μm)	− 0.04 (− 0.29, 0.21)	0.775	− 0.09 (− 0.49, 0.31)	0.654	6.9 × 10^–3 (− 0.28, 0.30)	0.963
Median straightness	0.14 (− 0.12, 0.4)	0.283	0.04 (− 0.43, 0.51)	0.873	0.23 (− 0.05, 0.50)	0.102
Average width (μm)	− 0.11 (− 0.36, 0.14)	0.394	− 0.29 (− 0.64, 0.07)	0.114	0.16 (− 0.13, 0.45)	0.272
Median alignment (in 44.91 μm × 44.91 μm)	− 3.0 × 10^–3 (− 0.24, 0.24)	0.980	0.07 (− 0.29, 0.43)	0.704	− 0.1 (− 0.39, 0.19)	0.517
Density (number of fibers/100 μm²)	0.23 (− 0.07, 0.52)	0.139	0.28 (− 0.14, 0.70)	0.193	0.15 (− 0.26, 0.56)	0.465
Median orientation (°)	− 0.06 (− 0.41, 0.3)	0.752	0.04 (− 0.49, 0.56)	0.894	− 0.1 (− 0.57, 0.36)	0.657
Dense volume
Fiber characteristic
Average length (μm)	0.12 (− 0.41, 0.65)	0.658	0.28 (− 0.48, 1.04)	0.466	− 0.07 (− 0.8, 0.67)	0.860
Median straightness	− 0.09 (− 0.61, 0.42)	0.723	0.39 (− 0.49, 1.27)	0.382	− 0.5 (− 1.07, 0.08)	0.092
Average width (μm)	0.12 (− 0.46, 0.7)	0.688	0.73 (− 5.5 × 10^–3, 1.47)	0.052	− 0.84 (− 1.54, − 0.15)	0.018
Median alignment (in 44.91 μm × 44.91 μm)	− 0.02 (− 0.5, 0.46)	0.927	− 0.2 (− 0.92, 0.52)	0.578	0.2 (− 0.36, 0.77)	0.482
Density (number of fibers/100 μm²)	− 0.12 (− 0.63, 0.4)	0.664	0.2 (− 0.52, 0.93)	0.585	− 0.54 (− 1.21, 0.14)	0.119
Median orientation (°)	− 0.1 (− 0.88, 0.69)	0.810	0.87 (− 0.13, 1.87)	0.087	− 0.7 (− 1.63, 0.23)	0.138
Local mammographic density of the biopsy target
% FGV
Fiber characteristic
Average length (μm)	− 0.02 (− 0.28, 0.23)	0.852	− 0.14 (− 0.54, 0.27)	0.506	0.07 (− 0.20, 0.35)	0.597
Median straightness	0.11 (− 0.16, 0.37)	0.433	− 0.07 (− 0.54, 0.41)	0.784	0.25 (− 0.03, 0.52)	0.077
Average width (μm)	− 0.17 (− 0.45, 0.11)	0.230	− 0.29 (− 0.69, 0.11)	0.155	0.01 (− 0.31, 0.34)	0.931
Median alignment (in 44.91 μm × 44.91 μm)	0.07 (− 0.18, 0.32)	0.571	0.12 (− 0.26, 0.49)	0.542	0.02 (− 0.29, 0.32)	0.921
Density (number of fibers/100 μm²)	0.32 (0.02, 0.61)	0.035	0.41 (− 0.01, 0.83)	0.056	0.20 (− 0.18, 0.58)	0.309
Median orientation (°)	− 0.09 (− 0.44, 0.26)	0.612	− 0.04 (− 0.60, 0.52)	0.886	− 0.10 (− 0.52, 0.32)	0.630
Dense volume
Fiber characteristic
Average length (μm)	− 0.07 (− 0.21, 0.08)	0.352	− 0.11 (− 0.31, 0.08)	0.258	− 0.02 (− 0.22, 0.19)	0.876
Median straightness	− 0.09 (− 0.23, 0.05)	0.220	− 0.04 (− 0.26, 0.18)	0.726	− 0.13 (− 0.32, 0.06)	0.180
Average width (μm)	− 0.08 (− 0.23, 0.08)	0.351	− 0.1 (− 0.32, 0.12)	0.366	− 0.03 (− 0.25, 0.19)	0.771
Median alignment (in 44.91 μm × 44.91 μm)	0.04 (− 0.11, 0.19)	0.625	0.09 (− 0.13, 0.32)	0.431	− 0.03 (− 0.21, 0.15)	0.747
Density (number of fibers/100 μm²)	− 0.04 (− 0.19, 0.12)	0.656	− 0.11 (− 0.34, 0.13)	0.384	0.06 (− 0.14, 0.26)	0.575
Median orientation (°)	0.11 (− 0.12, 0.33)	0.347	0.15 (− 0.17, 0.46)	0.355	0.06 (− 0.26, 0.37)	0.715
Local mammographic density in a peri− lesional 2 mm ring
% FGV
Fiber characteristic
Average length (μm)	− 8.3 × 10^–3 (− 0.28, 0.26)	0.952	− 0.14 (− 0.56, 0.28)	0.505	0.11 (− 0.19, 0.42)	0.471
Median straightness	0.17 (− 0.11, 0.44)	0.246	− 0.05 (− 0.54, 0.44)	0.851	0.34 (0.05, 0.63)	0.022
Average width (μm)	− 0.14 (− 0.43, 0.14)	0.328	− 0.31 (− 0.72, 0.10)	0.134	0.11 (− 0.23, 0.46)	0.511
Median alignment (in 44.91 μm × 44.91 μm)	0.06 (− 0.20, 0.33)	0.632	0.12 (− 0.27, 0.51)	0.555	− 4.1 × 10^–3 (− 0.33, 0.32)	0.98
Density (number of fibers/100 μm²)	0.35 (0.05, 0.64)	0.020	0.42 (− 0.01, 0.85)	0.057	0.25 (− 0.11, 0.62)	0.17
Median orientation (°)	− 0.09 (− 0.46, 0.27)	0.614	− 0.04 (− 0.62, 0.53)	0.881	− 0.12 (− 0.57, 0.34)	0.613
Dense volume
Fiber characteristic
Average length (μm)	− 0.02 (− 0.08, 0.04)	0.529	− 0.04 (− 0.14, 0.06)	0.385	4.7 × 10^–3 (− 0.06, 0.07)	0.884
Median straightness	− 0.01 (− 0.08, 0.05)	0.726	− 0.01 (− 0.12, 0.10)	0.850	− 0.01 (− 0.09, 0.07)	0.754
Average width (μm)	− 0.03 (− 0.10, 0.04)	0.438	− 0.03 (− 0.13, 0.07)	0.579	− 0.03 (− 0.11, 0.06)	0.541
Median alignment (in 44.91 μm × 44.91 μm)	0.02 (− 0.05, 0.08)	0.602	0.02 (− 0.07, 0.12)	0.607	7 × 10^–3 (− 0.07, 0.09)	0.863
Density (number of fibers/100 μm²)	7.9 × 10^–3 (− 0.07, 0.08)	0.832	− 3.1 × 10^–3 (− 0.12, 0.11)	0.958	0.02 (− 0.06, 0.10)	0.603
Median orientation (°)	0.04 (− 0.05, 0.12)	0.384	0.07 (− 0.07, 0.22)	0.323	0.01 (− 0.09, 0.11)	0.804

Bold indicate statistically signficant associations
Based on generalized estimating equation (GEE) models with independent correlation structure
Outcomes of the models were the square root of either the tissue composition or the MD measure. Collagen fiber characteristics were the independent variables of the models. Models also included the diagnosis of the ROIs and the case–control status of the woman. β is per 1− standard deviation of the fiber characteristic
MD: Mammographic density; FGV: Fibroglandular volume

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