Rationale and Objectives
To investigate whether quantitative kinetic analysis of lesions and background parenchyma in breast magnetic resonance imaging can elucidate differences between BRCA carriers and sporadic controls with high risk for breast cancer.
Materials and Methods
Fifty-nine BRCA and 59 control cases (49 benign, 10 malignant) were examined in this study. Principal component analysis was applied for quantitative analysis of dynamic signal in background parenchyma (B) and lesion (L) in terms of initial enhancement ratio (IER) and delayed enhancement ratio (DER).
Results
Control B-IER, B-DER, L-IER, and L-DER were higher than BRCA cases in all women and in women with benign lesions; statistically significant differences in B-IER and B-DER (all women: P = 0.02 and P = 0.02, respectively; benign only: P = 0.005 and P = 0.005, respectively). In the control cohort, B-IER and B-DER were higher in the premenopausal women than in the postmenopausal women ( P = 0.013 and 0.003, respectively), but not in the BRCA cohort; this led to significant differences in B-IER and B-DER between the control and the BRCA groups in the premenopausal women ( P = 0.01 and 0.01, respectively) but not in the postmenopausal women.
Conclusion
Results suggest possible differences in the vascular properties of background parenchyma between BRCA carriers and noncarriers and its association with menopausal status.
Introduction
BRCA 1 and BRCA 2 genes are involved in maintaining genome integrity by engaging in DNA repair and cell cycle checkpoint control, and are known as tumor suppressor genes . BRCA gene mutations are relatively common, affecting about 1 in 400 in the general population . Lifetime breast cancer risk in female BRCA mutation carriers is approximately 85% in BRCA 1 mutation carriers and about 45% in BRCA 2 mutation carriers . These women develop aggressive interval tumors that are often high grade, triple-negative breast cancers . Therefore, the American Cancer Society recommends annual screening breast magnetic resonance imaging (MRI), beginning at age 30, in all BRCA mutation carriers .
Recent studies have shown that the background parenchymal enhancement (BPE) from dynamic contrast-enhanced MRI (DCE-MRI) correlates with breast cancer risk . BPE refers to the enhancement of the normal-appearing fibroglandular tissue and is assessed on the contrast-enhanced image at the first time point after contrast agent injection . BPE reflects the vascularity of the breast parenchymal tissue and is sensitive to hormonal changes . BPE has been shown to vary with the menstrual cycle, increase with hormone replacement therapy, and decrease with menopause, antiestrogen therapies, and bilateral salpingo-oophorectomy . To date, no study has investigated possible differences between BPE of BRCA mutation carriers and nonmutation carriers and the effect of menopausal status on the BPE of these cohorts. Assessment of BPE kinetic properties of BRCA mutation carriers in comparison to nonmutation carriers may help better understand the role of BRCA in breast physiology and improve diagnostic accuracy of MRI in this population with an increased risk of familial breast cancer.
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Materials and Methods
Patient Data
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TABLE 1
Patient Characteristics
BRCA Cases Control Cases Malignant Benign Malignant Benign No. of patients 10 49 10 49 Age (years) 53.1 ± 10.03 40.33 ± 10.93 55.2 ± 10.63 41.94 ± 10.46 Estrogen receptor status Positive 4 (40%) N/A 10 (100%) N/A Negative 6 (60%) N/A 0 N/A Progesterone receptor status Positive 4 (40%) N/A 10 (100%) N/A Negative 6 (60%) N/A 0 N/A Premenopausal 2 (20%) 32 (65.3%) 5 (50%) 28 (57.1%) Menopausal 8 (80%) 17 (34.7%) 5 (50%) 21 (42.9%)
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MRI Data Acquisition
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Analysis of BPE Pattern
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Analysis of Breast Lesions
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Statistical Analysis
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Results
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TABLE 2
Radiographic Characteristics
BRCA Cases Control Cases Malignant Benign_P_ Value Malignant Benign_P_ Value No. of patients 10 49 10 49 BPE 0.33 0.39 None 3 (30%) 5 (10.2%) 2 (20%) 4 (8.2%) Mild 4 (40%) 20 (40.8%) 4 (40%) 18 (36.7%) Moderate 3 (30%) 20 (40.8%) 4 (40%) 18 (36.7%) Marked 0 4 (8.2%) 0 9 (18.4%) Mammographic density 0.10 0.15 Predominantly fatty 0 0 0 1 (2.0%) Scattered FGT 4 (40%) 6 (12.2%) 3 (30%) 10 (20.4%) Heterogeneously dense 4 (40%) 28 (57.2%) 7 (70%) 21 (42.9%) Extremely dense 2 (20%) 15 (30.6%) 0 17 (34.7%) Lesion kinetic curve 0.08 0.47 Type I 1 (10%) 24 (49%) 4 (40%) 24 (48.9%) Type II 7 (70%) 19 (38.8%) 6 (60%) 21 (42.9%) Type III 2 (20%) 6 (12.2%) 0 4 (8.2%) Lesion size 0.30 0.65 ≥2 cm 5 (50%) 16 (32.7%) 4 (40%) 16 (32.7%) <2 cm 5 (50%) 33 (67.3%) 6 (60%) 33 (67.3%) Lesion type 0.42 0.37 NME 8 (80%) 29 (59.2%) 8 (80%) 28 (57.1%) Mass 2 (20%) 17 (34.7%) 2 (20%) 18 (36.8%) Focus 0 3 (6.1%) 0 3 (6.1%)
BPE, background parenchymal enhancement; FGT, fibroglandular tissue; NME, non–mass-like enhancement.
The P values are from Fisher exact test (two groups) or the chi-square test (≥3 groups).
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Discussion
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Conclusions
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