Breast Parenchymal Enhancement Research Articles

Assessing Quantitative Parenchymal Features at Baseline Dynamic Contrast-enhanced MRI and Cancer Occurrence in Women with Extremely Dense Breasts.

Background Automated identification of quantitative breast parenchymal enhancement features on dynamic contrast-enhanced (DCE) MRI scans could provide added value in assessment of breast cancer risk in women with extremely dense breasts. Purpose To automatically identify quantitative properties of the breast parenchyma on baseline DCE MRI scans and assess their association with breast cancer occurrence in women with extremely dense breasts. Materials and Methods This study represents a secondary analysis of the Dense Tissue and Early Breast Neoplasm Screening trial. MRI was performed in eight hospitals between December 2011 and January 2016. After segmentation of fibroglandular tissue, quantitative features (including volumetric density, volumetric morphology, and enhancement characteristics) of the parenchyma were extracted from baseline MRI scans. Principal component analysis was used to identify parenchymal measures with the greatest variance. Multivariable Cox proportional hazards regression was applied to assess the association between breast cancer occurrence and quantitative parenchymal features, followed by stratification of significant features into tertiles. Results A total of 4553 women (mean age, 55.7 years ± 6 [SD]) with extremely dense breasts were included; of these women, 122 (3%) were diagnosed with breast cancer. Five principal components representing 96% of the variance were identified, and the component explaining the greatest independent variance (42%) consisted of MRI features relating to volume of enhancing parenchyma. Multivariable analysis showed that volume of enhancing parenchyma was associated with breast cancer occurrence (hazard ratio [HR], 1.09; 95% CI: 1.01, 1.18; P = .02). Additionally, women in the high tertile of volume of enhancing parenchyma showed a breast cancer occurrence twice that of women in the low tertile (HR, 2.09; 95% CI: 1.25, 3.61; P = .005). Conclusion In women with extremely dense breasts, a high volume of enhancing parenchyma on baseline DCE MRI scans was associated with increased occurrence of breast cancer as compared with a low volume of enhancing parenchyma. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Grimm in this issue.

Association of breast cancer risk, density, and stiffness: global tissue stiffness on breast MR elastography (MRE).

Quantify in vivo biomechanical tissue properties in various breast densities and in average risk and high-risk women using Magnetic Resonance Imaging (MRI)/MRE and examine the association between breast biomechanical properties and cancer risk based on patient demographics and clinical data. Patients with average risk or high-risk of breast cancer underwent 3.0T breast MR imaging and elastography. Breast parenchymal enhancement (BPE), density (from most recent mammogram), stiffness, elasticity, and viscosity were recorded. Within each breast density group (non-dense versus dense), stiffness, elasticity, and viscosity were compared across risk groups (average versus high). Separately for stiffness, elasticity, and viscosity, a multivariable logistic regression model was used to evaluate whether the MRE parameter predicted risk status after controlling for clinical factors. 50 average risk and 86 high-risk patients were included. Risk groups were similar in age, density, and menopausal status. Among patients with dense breasts, mean stiffness, elasticity, and viscosity were significantly higher in high-risk patients (N = 55) compared to average risk patients (N = 34; all p < 0.001). Stiffness remained a significant predictor of risk status (OR = 4.26, 95% CI [1.96, 9.25]) even after controlling for breast density, BPE, age, and menopausal status. Similar results were seen for elasticity and viscosity. A structurally based, quantitative biomarker of tissue stiffness obtained from MRE is associated with differences in breast cancer risk in dense breasts. Tissue stiffness could provide a novel prognostic marker to help identify high-risk women with dense breasts who would benefit from increased surveillance and/or risk reduction measures.

Relationship between degree of breast MRI background parenchymal enhancement and breast cancer subtype.

To observe the distribution of magnetic resonance imaging (MRI) breast parenchymal enhancement (BPE) among different breast cancer subtypes and to explore the relationship between the BPE and the breast cancer tumor type. A total of 150 consecutive patients with breast cancer underwent breast dynamic enhanced scanning image. According to the expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2) and Ki-67, the molecular subtypes were classified into Luminal-A, Luminal-B, HER-2 over- expression, and triple-negative breast cancer. The BPE of the whole breast was evaluated and categorized as minimal, mild, moderate, or marked according to the breast imaging reporting and data system (BI-RADS). The relationship between the distribution of BPE and the breast cancer subtypes was analyzed. In patients with mild BPE, the incidence of Luminal-B breast cancer was significantly increased, and there were statistical differences among the Luminal-B and the luminal-A, the HER-2 over-expressed type, and the triple-negative type (all P<0.01). In the marked BPE patients, the proportion of triple negative breast cancer was the highest, and there was statistical difference among the triple-negative type and the Luminal-A, the Luminal-B, and the HER-2 over-expression types (all P<0.05). The BPE can be served as an additional risk stratification index in the targeted screening of breast cancer type, which can offer reference value in the clinical diagnose and individualized treatment.

Preoperative breast MR imaging in newly diagnosed breast cancer: Comparison of outcomes based on mammographic modality, breast density and breast parenchymal enhancement

PurposeTo compare the role of MR for assessment of extent of disease in women newly diagnosed with breast cancer imaged with digital mammography (DM) alone versus digital breast tomosynthesis (DBT). MethodsRetrospective review was conducted of 401 consecutive breast MR exams (10/1/2013–7/31/2015) from women who underwent preoperative MR for newly diagnosed breast cancer by either DM or DBT, leaving 388 exams (201 DM and 187 DBT). MR detection of additional, otherwise occult, disease was stratified by modality, breast density, and background parenchymal enhancement. A true-positive finding was defined as malignancy in the ipsilateral-breast >2 cm away from the index-lesion or in the contralateral breast. Results50 additional malignancies were detected in 388 exams (12.9%), 37 ipsilateral and 13 contralateral. There was no difference in the MR detection of additional disease in women imaged by either DM versus DBT (p = 0.53). In patients with DM, there was no significant difference in the rate of MR additional cancer detection in dense versus non-dense breasts (p = 0.790). However, in patients with DBT, MR detected significantly more additional sites of malignancy in dense compared to non-dense breasts (p = 0.017). There was no difference in false-positive MR exams (p = 0.470) for DM versus DBT. For both DM and DBT cohorts, higher MR background parenchymal enhancement was associated with higher false-positive (p = 0.040) but no significant difference in true-positive exams. ConclusionsAmong patients with DBT imaging at cancer diagnosis, women with dense breasts appear to benefit more from preoperative MR than non-dense women. In women imaged only with DM, MR finds additional malignancy across all breast densities.

Contralateral parenchymal enhancement on breast MRI before and during neoadjuvant endocrine therapy in relation to the preoperative endocrine prognostic index

ObjectivesTo investigate whether contralateral parenchymal enhancement (CPE) on MRI during neoadjuvant endocrine therapy (NET) is associated with the preoperative endocrine prognostic index (PEPI) of ER+/HER2− breast cancer.MethodsThis retrospective observational cohort study included 40 unilateral ER+/HER2− breast cancer patients treated with NET. Patients received NET for 6 to 9 months with MRI response monitoring after 3 and/or 6 months. PEPI was used as endpoint. PEPI is based on surgery-derived pathology (pT- and pN-stage, Ki67, and ER-status) and stratifies patients in three groups with distinct prognoses. Mixed effects and ROC analysis were performed to investigate whether CPE was associated with PEPI and to assess discriminatory ability.ResultsThe median patient age was 61 (interquartile interval: 52, 69). Twelve patients had PEPI-1 (good prognosis), 15 PEPI-2 (intermediate), and 13 PEPI-3 (poor). High pretreatment CPE was associated with PEPI-3: pretreatment CPE was 39.4% higher on average (95% CI = 1.3, 91.9%; p = .047) compared with PEPI-1. CPE decreased after 3 months in PEPI-2 and PEPI-3. The average reduction was 24.4% (95% CI = 2.6, 41.3%; p = .032) in PEPI-2 and 29.2% (95% CI = 7.8, 45.6%; p = .011) in PEPI-3 compared with baseline. Change in CPE was predictive of PEPI-1 vs PEPI-2+3 (AUC = 0.77; 95% CI = 0.57, 0.96).ConclusionsCPE during NET is associated with PEPI-group in ER+/HER2− breast cancer: a high pretreatment CPE and a decrease in CPE during NET were associated with a poor prognosis after NET on the basis of PEPI.Key Points• Change in contralateral breast parenchymal enhancement on MRI during neoadjuvant endocrine therapy distinguished between patients with a good and intermediate/poor prognosis at final pathology.• Patients with a poor prognosis at final pathology showed higher baseline parenchymal enhancement on average compared to patients with a good prognosis.• Patients with an intermediate/poor prognosis at final pathology showed a higher average reduction in parenchymal enhancement after 3 months of neoadjuvant endocrine therapy.

Comparison of Segmentation Methods in Assessing Background Parenchymal Enhancement as a Biomarker for Response to Neoadjuvant Therapy.

Breast parenchymal enhancement (BPE) has shown association with breast cancer risk and response to neoadjuvant treatment. However, BPE quantification is challenging, and there is no standardized segmentation method for measurement. We investigated the use of a fully automated breast fibroglandular tissue segmentation method to calculate BPE from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for use as a predictor of pathologic complete response (pCR) following neoadjuvant treatment in the I-SPY 2 TRIAL. In this trial, patients had DCE-MRI at baseline (T0), after 3 weeks of treatment (T1), after 12 weeks of treatment and between drug regimens (T2), and after completion of treatment (T3). A retrospective analysis of 2 cohorts was performed: one with 735 patients and another with a final cohort of 340 patients, meeting a high-quality benchmark for segmentation. We evaluated 3 subvolumes of interest segmented from bilateral T1-weighted axial breast DCE-MRI: full stack (all axial slices), half stack (center 50% of slices), and center 5 slices. The differences between methods were assessed, and a univariate logistic regression model was implemented to determine the predictive performance of each segmentation method. The results showed that the half stack method provided the best compromise between sampling error from too little tissue and inclusion of incorrectly segmented tissues from extreme superior and inferior regions. Our results indicate that BPE calculated using the half stack segmentation approach has potential as an early biomarker for response to treatment in the hormone receptor–negative and human epidermal growth factor receptor 2–positive subtype.

Breast MRI background parenchymal enhancement as an imaging bridge to molecular cancer sub-type

PurposeTo evaluate the distribution of MRI breast parenchymal enhancement (BPE) among different breast cancer subtypes searching for any significant difference in terms of immunohistochemical and receptorial patterns (Estrogen Receptor -ER, Progesterone Receptor - PR, Human Epidermal Growth Factor Receptor 2 - HER2). Methods82 consecutive patients affected by breast cancer underwent breast DCE-MRI. Two radiologists retrospectively evaluated all subtracted MR enhanced images for classifying BPE. ER, PR and HER2 expression was assessed by immunohistochemical analysis. ER and PR status was evaluated using Allred score (positive values: score ≥3). The intensity of the cerbB-2 staining was scored as 0, 1+, 2+, or 3+ (positive values: ≥ 3+; negative:0 and 1+; 2+ value assessed with silver in-situ hybridization). Patients were classified into five categories based on cancer subtypes: Luminal A, Luminal B HER2 negative, Luminal B HER2 positive, HER2 positive non luminal, triple negative. The χ2 test was used for evaluating the significance of BPE type distribution into the five groups of tumor subtypes and the distribution of the five breast cancer subtypes among every single BPE type. The correlation of BPE with factors such as age, menopausal status and lesion diameter was investigated using multivariate regression analysis and logistic regression. Cohen's kappa statistics was used in order to assess inter-observer agreement for classifying BPE. Results6/82 cases were Luminal A-like (7.3%), 42/82 Luminal B-like (HER2-) (51.2%), 12/82 Luminal B-like (HER2+) (14.6%), 4/82 Non Luminal (HER+) (4.9%), 18/82 Triple Negative (ductal) (22%). 16/82 cases showed minimal BPE, 28/82 mild BPE, 22/82 moderate BPE, 16/82 marked BPE. Mild BPE pattern was significantly more prevalent (p = 0.0001) than other BPE types only in the luminal B (HER-) tumors. Moderate and marked BPE prevailed over minimal and mild, in triple negatives. Among all patients with mild BPE, luminal B (HER2-) tumors were significantly higher (p = 0.0001). Among all patients with marked BPE, triple negative subtypes were significantly higher (p = 0.0074). No significant confounder to BPE qualitative evaluation was found (p = 0.39). The inter-rater agreement in evaluating BPE patterns on MRI was almost perfect with Cohen’s k = 0.83. ConclusionsBPE could play a crucial role as an imaging bridge to molecular breast cancer subtype allowing an additional risk stratification in the field of breast MRI and targeted screening tests. Luminal B (HER2-) tumors could prevail in case of mild BPE on CE-MRI examinations and TN tumors in patients with marked BPE. Further studies on larger series are needed to confirm this hypothesis.

Comparison of background parenchymal enhancement and fibroglandular density at breast magnetic resonance imaging between BRCA gene mutation carriers and non-carriers

ObjectiveHigh background parenchymal enhancement and amount of fibroglandular tissue on breast magnetic resonance imaging are related to increased breast cancer risk. This study sought to compare these parameters between BRCA mutation carriers and non-carriers and to evaluate the potential implications of the findings for short term follow-up. Materials and Methods: Magnetic resonance imaging studies of known BRCA mutation carriers, were compared to age-matched non-carrier studies performed in the same center during the same period. The groups were compared for qualitative background parenchymal enhancement and amount of fibroglandular tissue using the Breast Imaging Reporting and Data System (BI-RADS). ResultsBreast parenchymal enhancement was high in up to one-third of the cohort: 22% of carriers and 33% of controls (p = 0.013). These results were sustained on separate analysis of menstrual-cycle-timed examinations. Amount of fibroglandular tissue was high in most cases: 62% of carriers and 75% of controls (p = 0.004). A BI-RADS final assessment score of 3 was more common in patients with high parenchymal enhancement, especially controls. ConclusionBRCA mutation carriers demonstrated lower levels of breast parenchymal enhancement and amount of fibroglandular tissue than age-matched non-carriers. These differences are probably influenced by hormonal status, as well as highlight different risks in distinctive subgroups of breast cancer (hormone-enriched, mutation-associated defective DNA damage repair), affecting considerations of preventive medical treatment. Differences in the indications for imaging between the carrier and non-carrier groups (screening for mutations and breast cancer evaluation, respectively) probably accounted for the higher rate of BI-RADS 3 in the control group.

Identification of Preoperative Magnetic Resonance Imaging Features Associated with Positive Resection Margins in Breast Cancer: A Retrospective Study.

ObjectiveTo determine which preoperative breast magnetic resonance imaging (MRI) findings and clinicopathologic features are associated with positive resection margins at the time of breast-conserving surgery (BCS) in patients with breast cancer.Materials and MethodsWe reviewed preoperative breast MRI and clinicopathologic features of 120 patients (mean age, 53.3 years; age range, 27–79 years) with breast cancer who had undergone BCS in 2015. Tumor size on MRI, multifocality, patterns of enhancing lesions (mass without non-mass enhancement [NME] vs. NME with or without mass), mass characteristics (shape, margin, internal enhancement characteristics), NME (distribution, internal enhancement patterns), and breast parenchymal enhancement (BPE; weak, strong) were analyzed. We also evaluated age, tumor size, histology, lymphovascular invasion, T stage, N stage, and hormonal receptors. Univariate and multivariate logistic regression analyses were used to determine the correlation between clinicopathological features, MRI findings, and positive resection margins.ResultsIn univariate analysis, tumor size on MRI, multifocality, NME with or without mass, and segmental distribution of NME were correlated with positive resection margins. Among the clinicopathological factors, tumor size of the invasive breast cancer and in situ components were significantly correlated with a positive resection margin. Multivariate analysis revealed that NME with or without mass was an independent predictor of positive resection margins (odds ratio [OR] = 7.00; p < 0.001). Strong BPE was a weak predictor of positive resection margins (OR = 2.59; p = 0.076).ConclusionNon-mass enhancement with or without mass is significantly associated with a positive resection margin in patients with breast cancer. In patients with NME, segmental distribution was significantly correlated with positive resection margins.

Contrast enhancement kinetics of normal breast parenchyma in dynamic MR mammography: effects of menopausal status, oral contraceptives, and postmenopausal hormone therapy

To investigate effects of menopausal status, oral contraceptives (OC), and postmenopausal hormone therapy (HT) on normal breast parenchymal contrast enhancement (CE) and non-mass-like enhancing areas in magnetic resonance mammography (MRM). A total of 459 female volunteers (mean age 49.1 ± 12.5 years) underwent T1-weighted 3D MRM 1-5 min after bolus injection of gadobutrol. Quantitative analysis was performed in normal breast parenchyma by manually tracing regions of interest and calculating percentage CE. Semiquantitative analysis was performed in non-mass-like enhancing areas, and signal intensity changes were characterised by five predefined kinetic curve types. The influence of OC (n = 69) and HT (n = 24) on CE was studied using random effects models. Breast parenchymal enhancement was significantly higher in premenopausal than in postmenopausal women (P < 0.001). CE decreased significantly with the use of OC (P = 0.01), while HT had negligible effects (P = 0.52). Prevalence of kinetic curve types of non-mass-like enhancement differed strongly between pre- and postmenopausal women (P < 0.0001), but was similar in OC users and non-OC users (P = 0.61) as well as HT users and non-HT users (P = 0.77). Normal breast parenchymal enhancement and non-mass-like enhancing areas were strongly affected by menopausal status, while they were not affected by HT use and only moderately by OC use. Breast parenchymal enhancement at MR mammography is stronger in premenopausal than postmenopausal women. The prevalence of strong enhancing non-mass-like areas is greater before menopause. Such enhancing non-mass-like areas may impair lesion detection in premenopausal women. Breast parenchymal enhancement is only marginally affected by hormone use. Discontinuation of hormone use before MR mammography may be unnecessary.

The effect of acute aromatase inhibition on breast parenchymal enhancement in magnetic resonance imaging

The breast is highly hormonally sensitive especially to the sex steroid hormone estrogen. Both physiological and iatrogenic steroid hormone modifications could affect how the breast tissue may appear in breast imaging techniques. We hypothesized that estrogen deprivation therapy could reduce breast nonspecific enhancement on magnetic resonance imaging (MRI). This study was a prospective pilot phase II clinical trial. The study was approved by Health Canada and the institutional research ethics board, and participants signed informed consent forms. Sixteen healthy postmenopausal women were enrolled, and 14 completed the study. Baseline breast MRI was done followed 1 month later by administration of a high-dose aromatase inhibitor (letrozole 12.5 mg/day) for 3 successive days before a second breast MRI. Background breast parenchymal enhancement was compared between the pretreatment and posttreatment studies. There was a statistically significant reduction of the average background breast enhancement after treatment with aromatase inhibitors compared with baseline MRI. Of particular interest, specific areas of benign breast enhancement were reduced after aromatase inhibitor treatment. No significant adverse effects were recorded using this relatively high dose of the aromatase inhibitors. This preliminary study provided evidence that aromatase inhibitors could reduce the parenchymal background enhancement of benign breast tissue during MRI and may improve the specificity of the technique.