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. 2021 Nov 9;23:105. 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

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