Introduction
Methods
Study populations and data collection
Analytic sample
The NCI Clinical Genetics Branch’s Breast Imaging Study
The NCI/NNMC Susceptibility to Breast Cancer Study
Assessment of mammographic density
Computerized assessment of mammographic parenchymal patterns
Radiographic texture analysis (RTA) of computer-extracted features
Statistical analyses
Selection of participants for the training and testing datasets
Stepwise feature selection using linear discriminant analysis
Merging of computer-extracted features
Performance evaluation and related statistical analyses
Results
Distribution of patient characteristics in the training and testing datasets
Training dataset (n = 177) | Testing dataset (n = 60) | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Variable | Non-carriers (n = 70) | UnaffectedBRCA1/2carriers (n = 107) | P-value for mutation carriers versus non-carriers | Non-carriers (n = 30) | UnaffectedBRCA1/2carriers (n = 30) | P-value for mutation carriers versus non-carriers | P-value2 | P-value3 | ||||
Mean (SD) | Range | Mean (SD) | Range | P-value fromt-test | Mean (SD) | Range | Mean (SD) | Range | P-value fromt-test | P-value fromt-test | ||
Age, years | 48.8 (9.6) | 25, 79 | 37.7 (8.5) | 22, 55 |
<0.0001
| 47.2 (10.1) | 25, 74 | 37.8 (8.9) | 25, 55 |
0.0003
| 0.44 | 0.95 |
Body mass index1 | 26.2 (5.7) | 18.0, 45.5 | 25.5 (5.4) | 17.9, 48.2 | 0.41 | 27.3 (6.7) | 18.3, 49.5 | 25.9 (5.9) | 19.5, 40.0 | 0.37 | 0.38 | 0.74 |
Percent mammographic density, unadjusted | 32.2 (15.2) | 3.5, 76.3 | 37.6 (14.7) | 2.8, 70.8 |
0.02
4
| 30.7 (14.7) | 2.0, 53.7 | 35.5 (14.2) | 4.8, 68.4 | 0.214 | 0.66 | 0.47 |
Number
|
%
*
|
Number
|
%
*
|
P
-value from chi square
5
|
Number
|
%
*
|
Number
|
%
*
|
P
-value from chi square
5
|
P
-value from chi square
5
| ||
White, non-Hispanic | 63 | 90.0 | 107 | 100.0 |
0.001
| 25 | 83.3 | 30 | 100.0 | 0.05 | 0.35 | 1.00 |
College graduate | 52 | 74.3 | 83 | 77.6 | 0.62 | 21 | 70.0 | 22 | 73.3 | 0.77 | 0.66 | 0.63 |
Ever smoked | 17 | 24.3 | 35 | 32.7 | 0.23 | 13 | 43.3 | 8 | 26.7 | 0.18 | 0.06 | 0.53 |
Age at menarche, years | 0.78 | 0.87 | 0.96 | 0.40 | ||||||||
<12 | 10 | 14.5 | 13 | 12.3 | 5 | 16.7 | 6 | 20.0 | ||||
12 to 13 | 42 | 60.9 | 70 | 66.0 | 18 | 60.0 | 16 | 53.3 | ||||
≥14 | 17 | 24.6 | 23 | 21.7 | 7 | 23.3 | 8 | 26.7 | ||||
Missing | 1 | 1 | ||||||||||
Parous | 52 | 74.3 | 61 | 57.0 |
0.02
| 24 | 80.0 | 13 | 43.3 |
0.004
| 0.54 | 0.18 |
Age at first birth, years | 0.09 |
0.02
| 0.27 | 0.62 | ||||||||
<30 | 36 | 51.4 | 41 | 38.3 | 19 | 63.3 | 10 | 33.3 | ||||
≥30 or nulliparous | 34 | 48.6 | 66 | 61.7 | 11 | 36.7 | 20 | 66.7 | ||||
Ever used oral contraceptives | 51 | 72.9 | 96 | 89.7 |
0.004
| 24 | 80.0 | 26 | 86.7 | 0.49 | 0.45 | 0.64 |
Menopausal status |
<0.0001
| 0.08 | 0.59 | 0.83 | ||||||||
Premenopausal | 44 | 64.7 | 60 | 56.1 | 16 | 57.1 | 19 | 63.3 | ||||
Postmenopausal, natural | 4 | 5.9 | 6 | 5.6 | 4 | 14.3 | 2 | 6.7 | ||||
Postmenopausal, surgical | 9 | 13.2 | 40 | 37.4 | 4 | 14.3 | 9 | 30.0 | ||||
Postmenopausal, unknown | 11 | 16.2 | 1 | 0.9 | 4 | 14.3 | 0 | 0.0 | ||||
Missing | 2 | 0 | 2 | 0 | ||||||||
Menopausal hormone therapy | 0.97 | 0.31 | 0.95 | 0.30 | ||||||||
Never | 48 | 68.6 | 74 | 69.2 | 20 | 66.7 | 25 | 83.3 | ||||
Former | 10 | 14.3 | 16 | 15.0 | 5 | 16.7 | 2 | 6.7 | ||||
Current | 12 | 17.1 | 17 | 15.9 | 5 | 16.7 | 3 | 10.0 | ||||
Breast biopsy prior to enrollment | 21 | 30.0 | 26 | 24.3 | 0.40 | 5 | 16.7 | 7 | 23.3 | 0.52 | 0.16 | 0.91 |
Descriptive characteristics of selected computer-extracted features
Correlation with percent mammographic density (n = 237) | Correlation with age (n = 237) | Non-carriers (n = 100) | UnaffectedBRCA1/2carriers (n = 137) | |||||||
---|---|---|---|---|---|---|---|---|---|---|
Feature type and number | Feature1 | Definition | r* | P-value | r* | P-value | Mean (SD) | Range | Mean (SD) | Range |
Gray-level magnitude-based features:
| ||||||||||
M1 | AVE | Average gray value within ROI; higher values correspond to denser region |
0.31
|
<0.0001
| 0.01 | 0.89 | 139.6 (26.1) | 69.0, 223.5 | 134.1 (28.9) | 59.0, 242.0 |
M2 | MinCDF | Gray value corresponding to the 5% region cutoff on cumulative density function; higher values correspond to denser region |
-0.13
|
0.04
|
0.23
|
0.0005
| 98.0 (23.6) | 35.0, 162.0 | 78.1 (27.3) | 15.0, 210.0 |
M3 | Balance | Ratio of (95% CDF-AVE) to (AVE-5% CDF); related to skewness; values less than one correspond to having an ROI that is skewed toward relatively denser values |
-0.32
|
<0.0001
| -0.04 | 0.49 | 1.07 (0.42) | 0.45, 3.31 | 1.11 (0.40) | 0.38, 2.33 |
Texture-based features:
| ||||||||||
T1 | Energy | Measure of image homogeneity; higher values correspond to being more homogeneous |
-0.30
|
<0.0001
|
0.19
|
0.003
| 0.004 (0.011) | 0.0, 0.109 | 0.003 (0.004) | 0.0, 0.028 |
T2 | MaxF (COOC) | Largest number of a gray value pair in the co-occurrence matrix; measure of image homogeneity; higher values correspond to being more homogeneous |
-0.24
|
0.0002
|
0.15
|
0.02
| 0.012 (0.024) | 0.001, 0.239 | 0.010 (0.017) | 0.001, 0.145 |
Relationships between computer-extracted mammographic features and BRCA1/2 mutation status: original training and testing datasets
Training dataset* | Testing dataset | Testing dataset results | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Description | Number of non-carriers | Number of carriers | Odds ratio | 95% CI | P-value | Odds ratio | 95% CI | P-value | OR | 95% CI | P-value | AUC | SE |
Unadjusted
|
Adjusted for age
|
Adjusted for age and PMD
| |||||||||||
Percent mammographic density (PMD) alone | 30 | 30 | 1.022 | (0.99, 1.06) | 0.21 | 1.002 | (0.96, 1.04) | 0.96 | N/A | 0.59 | 0.07 | ||
Features alone1 | 30 | 30 |
2.00
3
|
(1.59, 2.51)
|
0.02
|
1.93
3
|
(1.53, 2.42)
|
0.03
|
1.93
3
|
(1.54, 2.43)
|
0.03
| 0.68 | 0.07 |
Features1 + PMD | 30 | 30 |
2.10
3
|
(1.67, 2.65)
|
0.01
|
2.03
3
|
(1.62, 2.56)
|
0.03
| N/A | 0.72 | 0.07 |