Breast cancer detection and tumor characteristics in BRCA1 and BRCA2 mutation carriers.

PURPOSE: To describe imaging findings, detection rates, and tumor characteristics of breast cancers in a large series of patients with BRCA1 and BRCA2 mutations to potentially streamline screening strategies. METHODS: An IRB-approved, HIPAA-compliant retrospective analysis of 496 BRCA mutation carriers diagnosed with breast carcinoma from 1999 to 2013 was performed. Institutional database and electronic medical records were reviewed for mammography and MRI imaging. Patient and tumor characteristics including age at diagnosis, tumor histology, grade, receptor, and nodal status were recorded. RESULTS: Tumors in BRCA1 mutation carriers were associated exhibited significantly higher nuclear and histological grade compared to BRCA2 (p < 0.001). Triple-negative tumors were more frequent in BRCA1 mutation carriers, whereas hormone receptor-positive tumors were more frequent in BRCA2 mutation carriers (p < 0.001). BRCA2 mutation carriers more frequently presented with ductal carcinoma in situ (DCIS) alone 14% (35/246) and cancers more frequently exhibiting calcifications (p < 0.001). Mammography detected fewer cancers in BRCA1 mutation carriers compared to BRCA2 (p = 0.04): 81% (186/231) BRCA1 versus 89% (212/237) BRCA2. MRI detected 99% cancers in each group. Mammography detected cancer in two patients with false-negative MRI (1 invasive cancer, 1 DCIS). Detection rates on both mammography and MRI did not significantly differ for women over 40 years and women below 40 years. CONCLUSIONS: Breast cancers in BRCA1 mutation carriers are associated with more aggressive tumor characteristics compared to BRCA2 and are less well seen on mammography. Mammography rarely identified cancers not visible on MRI. Thus, the omission of mammography in BRCA1 mutation carriers screened with MRI can be considered.

Breast MR imaging for the assessment of residual disease following initial surgery for breast cancer with positive margins.

OBJECTIVES: To determine the accuracy of post-operative MR in predicting residual disease in women with positive margins, emphasizing the size thresholds at which residual disease can be confidently identified. METHODS: This IRB-approved HIPAA-compliant retrospective study included 175 patients with MR after positive margins following initial surgery for breast cancer. Two expert readers independently re-evaluated MR images for evidence of residual disease at the surgical cavity and multifocal/multicentric disease. All patients underwent definitive surgery and MR findings were correlated to histopathology. RESULTS: 139/175 (79.4%) patients had residual disease at surgery. Average overall sensitivity, specificity, PPV and NPV for residual disease at the surgical cavity were 73%, 72%, 91% and 45%, respectively. The readers identified 42/45 (93%, reader 1) and 43/45 (95%, reader 2) patients with residual invasive disease at the cavity of ≥5 mm and 22/22 (100%, both readers) patients with disease ≥10 mm. Average sensitivity, specificity, PPV and NPV for unknown multifocal/multicentric disease were 90%, 96%, 93% and 86%, respectively. CONCLUSIONS: Post-operative breast MR can accurately depict ≥5-mm residual disease at the surgical cavity and unsuspected multifocal/multicentric disease. These findings have the potential to lead to more appropriate selection of second surgical procedures in women with positive margins. KEY POINTS: • Post-operative breast MRI accurately defines residual disease of ≥5 mm. • Surgical cavity sensitivities were high for both invasive carcinoma and DCIS. • Post-surgical changes and very small residual disease (<5 mm) may overlap. • Post-operative breast MRI may help planning an accurate re-resection.

Is the assessment of the central skeleton sufficient for osseous staging in breast cancer patients? A retrospective approach using bone scans.

OBJECTIVE: By analyzing bone scans we aimed to determine whether the assessment of the central skeleton is sufficient for osseous staging in breast cancer patients. This might be of interest for future staging modalities, especially positron emission tomography/computed tomography, usually sparing the peripheral extremities, as well as the skull. MATERIALS AND METHODS: In this retrospective study, a total of 837 bone scans for initial staging or restaging of breast cancer were included. A total of 291 bone scans in 172 patients were positive for bone metastases. The localization and distribution of the metastases were re-evaluated by two readers in consensus. The extent of the central skeleton involvement was correlated to the incidence of peripheral metastases. RESULTS: In all 172 patients bone metastases were seen in the central skeleton (including the proximal third of humerus and femur). In 34 patients (19.8 %) peripheral metastases of the extremities (distally of the proximal third of humerus and femur) could be detected. Sixty-four patients (37.2 %) showed metastases of the skull. Summarizing the metastases of the distal extremities and skull, 79 patients (45.9 %) had peripheral metastases. None of the patients showed peripheral metastases without any affliction of the central skeleton. The incidence of peripheral metastases significantly correlated with the extent of central skeleton involvement (p<0.001). CONCLUSIONS: Regarding bone scans, an isolated metastatic spread to the peripheral skeleton without any manifestation in the central skeleton seems to be the exception. Thus, the assessment of the central skeleton should be sufficient in osseous breast cancer staging and restaging. However, in case of central metastases, additional imaging of the periphery should be considered for staging and restaging.

Overexpression of CD36 and acyl-CoA synthetases FATP2, FATP4 and ACSL1 increases fatty acid uptake in human hepatoma cells.

BACKGROUND: Understanding the mechanisms of long chain fatty acid (LCFA) uptake in hepatic cells is of high medical importance to treat and to prevent fatty liver disease (FLD). ACSs (Acyl-CoA synthetases) are a family of enzymes that catalyze the esterification of fatty acids (FA) with CoA. Recent studies suggest that ACS enzymes drive the uptake of LCFA indirectly by their enzymatic activity and could promote special metabolic pathways dependent on their localization.The only protein located at the plasma membrane which has consistently been shown to enhance FA uptake is CD36. AIMS: The current study investigated whether ACSs and CD36 could regulate hepatic LCFA uptake. METHODS AND RESULTS: FATP2 and FATP4 were both localized to the ER of HuH7 and HepG2 cells as shown by double immunofluorescence in comparison to marker proteins. ACSL1 was located at mitochondria in both cell lines. Overexpression of FATP2, FATP4 and ACSL1 highly increased ACS activity as well as the uptake of [3H]-oleic acid and fluorescent Bodipy-C12 (B12) fatty acid. Quantitative FACS analysis showed a correlation between ACS expression levels and B12 uptake. FATP2 had the highest effect on B12 uptake of all proteins tested. CD36 was mainly localized at the plasma membrane. Whereas [3H]-oleic acid uptake was increased after overexpression, CD36 had no effect on B12 uptake. CONCLUSION: Uptake of LCFA into hepatoma cells can be regulated by the expression levels of intracellular enzymes. We propose that ACS enzymes drive FA uptake indirectly by esterification. Therefore these molecules are potential targets for treatment of nonalcoholic fatty liver disease (NAFLD) or steatohepatitis (NASH).

Simultaneous Multislice Diffusion-Weighted Imaging of the Kidneys at 3 T.

PURPOSE: The aim of this study was to compare respiratory-triggered diffusion-weighted imaging with simultaneous-multislice acceleration (SMS-RT-DWI) to a standard free-breathing echoplanar DWI (s-DWI) for 3 T renal imaging with respect to image quality and artifacts. MATERIALS AND METHODS: A total of 40 patients who had undergone renal magnetic resonance imaging were included in this retrospective analysis of a prospectively planned cohort study. All examinations were performed on a 3 T whole-body magnetic resonance system. Both s-DWI and SMS-RT-DWI were obtained and images were independently reviewed by 2 radiologists on a 5-point Likert scale with respect to overall preference and image quality, renal edge and parenchymal sharpness, cortico-medullary differentiation, and sequence-related artifacts. Furthermore, discernibility of renal lesions was assessed. The signal-to-noise ratio (SNR) was measured from SNR maps. The derived mean apparent diffusion coefficients were also compared. Qualitative parameters were assessed with the Wilcoxon rank-sum test, and quantitative parameters, with the Student t test. RESULTS: Overall image quality, renal edge, and parenchymal sharpness of SMS-RT-DWI were rated as superior to s-DWI by the readers, with fewer sequence-related artifacts (P < 0.01 for all). Lesion discernibility was significantly improved for SMS-RT-DWI (P < 0.01). Both readers preferred SMS-RT-DWI to s-DWI in all cases (40/40). The acquisition time for SMS-RT-DWI was 30% shorter than for s-DWI. Mean SNR heterogeneity of SMS-RT-DWI at b = 800 s/mm was statistically significantly lower than s-DWI, whereas mean SNR was significantly higher for SMS-RT-DWI. Mean apparent diffusion coefficient values from both sequences were comparably homogeneous throughout the kidneys. CONCLUSION: Simultaneous multislice DWI of the kidney at 3 T with respiratory triggering yields substantially improved image quality and lesion discernibility compared with standard single-shot echoplanar DWI with a 30% reduction in scan acquisition time.

Evaluation of a new image reconstruction method for digital breast tomosynthesis: effects on the visibility of breast lesions and breast density.

OBJECTIVE: To compare image quality and breast density of two reconstruction methods, the widely-used filtered-back projection (FBP) reconstruction and the iterative heuristic Bayesian inference reconstruction (Bayesian inference reconstruction plus the method of total variation applied, HBI). METHODS: Thirty-two clinical DBT data sets with malignant and benign findings, n = 27 and 17, respectively, were reconstructed using FBP and HBI. Three experienced radiologists evaluated the images independently using a 5-point visual grading scale and classified breast density according to the American College of Radiology Breast Imaging-Reporting And Data System Atlas, fifth edition. Image quality metrics included lesion conspicuity, clarity of lesion borders and spicules, noise level, artifacts surrounding the lesion, visibility of parenchyma and breast density. RESULTS: For masses, the image quality of HBI reconstructions was superior to that of FBP in terms of conspicuity,clarity of lesion borders and spicules (p < 0.01). HBI and FBP were not significantly different in calcification conspicuity. Overall, HBI reduced noise and supressed artifacts surrounding the lesions better (p < 0.01). The visibility of fibroglandular parenchyma increased using the HBI method (p < 0.01). On average, five cases per radiologist were downgraded from BI-RADS breast density category C/D to A/B. CONCLUSION: HBI significantly improves lesion visibility compared to FBP. HBI-visibility of breast parenchyma increased, leading to a lower breast density rating. Applying the HBIR algorithm should improve the diagnostic performance of DBT and decrease the need for additional imaging in patients with dense breasts. ADVANCES IN KNOWLEDGE: Iterative heuristic Bayesian inference (HBI) image reconstruction substantially improves the image quality of breast tomosynthesis leading to a better visibility of breast carcinomas and reduction of the perceived breast density compared to the widely-used filtered-back projection (FPB) reconstruction. Applying HBI should improve the accuracy of breast tomosynthesis and reduce the number of unnecessary breast biopsies. It may also reduce the radiation dose for the patients, which is especially important in the screening context.

The Assessment of Background Parenchymal Enhancement (BPE) in a High-Risk Population: What Causes BPE?

OBJECTIVE: To investigate promoting factors for background parenchymal enhancement (BPE) in MR mammography (MRM). METHODS: 146 patients were retrospectively evaluated, including 91 high-risk patients (50 BRCA patients, 41 patients with elevated lifetime risk). 56 screening patients were matched to the high-risk cases on the basis of age. The correlation of BPE with factors such as fibroglandular tissue (FGT), age, menopausal status, breast cancer, high-risk precondition as well as motion were investigated using linear regression. RESULTS: BPE positively correlated with FGT (P<.001) and negatively correlated with menopausal status (P<.001). Cancer did not show an effect on BPE (P>.05). A high-risk precondition showed a significant impact on the formation of BPE (P<.05). However, when corrected for motion, the correlation between BPE and a high-risk precondition became weak and insignificant, and a highly significant association between BPE and motion was revealed (P<.01). CONCLUSION: BPE positively correlated with FGT and negatively correlated with age. Cancer did not have an effect on BPE. A high-risk precondition appears to have a negative effect on BPE. However, when corrected for motion, high-risk preconditions became insignificant. Technical as well as physiological influences seem to play an important role in the formation of BPE.

Value of Additional Digital Breast Tomosynthesis for Preoperative Staging of Breast Cancer in Dense Breasts.

AIM: This retrospective study was initiated to determine the diagnostic value of additional preoperative breast tomosynthesis (DBT) for breast cancer staging in dense breasts. PATIENTS AND METHODS: Sixty-six patients (69 breasts) with findings of American College of Radiology category 3 or 4 with Breast Imaging Reporting and Data System 5, 6 or 0 were included. All patients underwent digital mammography and additional DBT. RESULTS: A total of 40/69 (58%) cancers were detected on both mammography and DBT, 23 (33.3%) were only seen on DBT (p=0.0001); 6/69 (8.7%) carcinomas were not detected by either method, of which three were invasive lobular carcinomas. Sensitivity for multifocal/multicentric disease was significantly higher on DBT (12/19, 63.2%) compared to mammography (4/19, 21.1%) (p=0.02), specificity was comparable (96.0% vs. 90.0%). Multifocal/multicentric disease was not detected on mammography nor DBT in 7/19 (36.8%) patients, including three invasive lobular carcinomas. CONCLUSION: DBT may significantly improve preoperative breast cancer staging in patients with dense breasts compared to conventional mammography alone. Nevertheless, limitations have to be expected in the case of invasive lobular carcinoma.

Prognostic Value of "Prepectoral Edema" in MR-mammography.

BACKGROUND/AIM: Previous studies have indicated a highly significant correlation between invasive tumors and accompanying prepectoral edema (PE) in MR-mammography (MRM). The aim of the present study was to identify prognostic factors associated with PE as a diagnostic sign. MATERIALS AND METHODS: A total of 1,109 consecutive MRM exams were included in this study. Exclusion criteria were previous operation, biopsy, intervention, chemotherapy, hormone replacement therapy (HRT) or previous mastitis. One hundred and sixty-two patients with 180 lesions were evaluated and histologically correlated. Diagnostic evaluations were performed by four experienced radiologists in consensus. RESULTS: One hundred and eighty lesions included 104 malignant lesions (93 invasive and 11 non-invasive) and 76 benign lesions. PE was detected significantly more frequently in presence of lymphangiosis carcinomatosa ((53.8%; 14/26) vs. (9.8%; 4/41)) (p<0,000). PE significantly correlates with positive axillary nodal status ((19.4% (12/62) vs. 44.4% (12/27)) (p=0.020), as well as pathologic enhancement of the pectoral muscle (5.4% (5/93) vs. 22.7% (20/88)) (p=0,015). PE significantly correlates with higher tumor grading (G3) (33.9% vs. 13.9%) (p<0.05). There was no significant difference in a positive vs. negative estrogen (p=0.681) and progesterone (p=0.751) and/or human epidermal growth factor receptor-2 (HER-2) (p=0.726) receptor status accompanied by PE. CONCLUSION: The presence of PE may be a strong prognostic indicator for lymphatic spread and the cancerous infiltration of lymph nodes. It is also associated with the infiltration of the pectoral muscle, as well as high tumor grading. There is no correlation between prepectoral edema and positive tumor receptor status.

The value of "constant sharpness" as a diagnostic sign in MR-Mammography.

PURPOSE: To examine "constant lesion sharpness" as a morphological diagnostic sign in the differential diagnosis between benign and malignant lesions. MATERIAL AND METHODS: This prospective study had institutional review board approval and was HIPAA compliant. In total 1014 consecutive patients were examined (mean age 55 years ± 13 years) and evaluated in our University hospital towards the morphological shape of the lesion borders. The "Constant sharpness Sign" was defined as a lesion remaining continuously sharp for the duration of the dynamic scan. Inclusion criteria were unclear findings (e.g. BIRADS III/IV), Preoperative staging (BRIDAS IV/V), and referred patients from local clinic of gynecology. Exclusion criteria were MRM-examination ≤1 year before, status after surgery and/or biopsy, chemotherapy and/or radiation therapy. Reference Standard was histological verification. Images were diagnosed by two experienced radiologists in consensus, blinded to the standard of reference. RESULTS: 1014 patients with 1084 lesions (436 benign, 648 malignant lesions) were included into the study. 41.5% of benign lesions and 6.8% (181/436) of malignant lesions displayed a constant sharpness as an accompanying morphological sign (P < 0.001). This resulted in a sensitivity of 41.5%, specificity of 93.2%, a positive likelihood ratio of 6.1%, a negative likelihood ratio of 0.63 and an odd's ratio of 9,7%. SUMMARY AND CONCLUSION: The constant sharpness sign seems to be an accurate predictor of benign breast lesions, which may help to increase the accuracy of MRM as a morphological sign.

Impact of Tumor Localization and Method of Preoperative Biopsy on Sentinel Lymph Node Mapping After Periareolar Nuclide Injection.

BACKGROUND: To evaluate whether tumor localization and method of preoperative biopsy affect sentinel lymph node (SLN) detection after periareolar nuclide injection in breast cancer patients. METHODS AND FINDINGS: 767 breast cancer patients were retrospectively included. For lymphscintigraphy periareolar nuclide injection was performed and the SLN was located by gamma camera. Patient and tumor characteristics were correlated to the success rate of SLN mapping. SLN marking failed in 9/61 (14.7%) patients with prior vacuum-assisted biopsy and 80/706 (11.3%) patients with prior core needle biopsy. Individually evaluated, biopsy method (p = 0.4) and tumor localization (p = 0.9) did not significantly affect the SLN detection rate. Patients with a vacuum-assisted biopsy of a tumor in the upper outer quadrant had a higher odds ratio of failing in SLN mapping (OR 3.8, p = 0.09) compared to core needle biopsy in the same localization (OR 0.9, p = 0.5). CONCLUSIONS: Tumor localization and preoperative biopsy method do not significantly impact SLN mapping with periareolar nuclide injection. However, the failure risk tends to rise if vacuum-assisted biopsy of a tumor in the upper outer quadrant is performed.

Is "prepectoral edema" a morphologic sign for malignant breast tumors?

RATIONALE AND OBJECTIVES: A variety of morphologic and kinetic signs of benign or malignant breast lesions contribute to a final diagnosis and differential diagnosis in magnetic resonance (MR) mammography (MRM). As a new sign, prepectoral edema (PE) in patients without any history of previous biopsy, operation, radiation, or chemotherapy was detected during routine breast MR examinations. The purpose of this study was to retrospectively evaluate the role of this morphologic sign in the differential diagnosis of breast lesions. MATERIALS AND METHODS: Between January 2005 and October 2006, a total of 1109 consecutive MRM examinations have been performed in our institution. In this study, only patients who would later be biopsied or operated in our own hospital were included. They had no previous operation, biopsy, intervention, chemotherapy, hormone replacement therapy, or previous mastitis. In total, 162 patients with 180 lesions were included, histologically correlated later-on by open biopsy (124 patients and 136 lesions) or core biopsy (38 patients and 44 lesions). The evaluations were performed by four experienced radiologists in consensus. RESULTS: One hundred eighty evaluated lesions included 104 malignant lesions (93 invasive and 11 noninvasive cancers) and 76 benign lesions. PE was detected in 2.6% of benign lesions (2 of 76), in none of the Ductal cacinoma in situ (DCIS) cases (0 of 11), and in 25.8% of malignant lesions (24 of 93; P < .000). PE was found significantly more frequently in presence of malignant tumors >2 cm in diameter (48.5%, 17 of 35 vs. 13.8%, 8 of 58; P < .001). PE was not statistically associated to malignant tumor type, presence or absence of additional DCIS, and number of lesions. This resulted in the following diagnostic parameters for PE as an indicator for malignancy: sensitivity of 19.3%, specificity of 97.3%, positive predictive value (PPV) of 92.3%, negative predictive value of 48%, and accuracy of 57.7%. CONCLUSIONS: In case of occurrence, the "PE sign" seems to be a specific indicator for malignant tumors with a high PPV, independent from its entity.

Characteristics of axillary lymph nodes apparent on dynamic contrast-enhanced breast MRI in healthy women.

The study was initiated to characterize and better understand the natural characteristics of axillary lymph nodes (LNs) apparent on dynamic breast magnetic resonance imaging (MRI). The most important finding in 71 subjects that included healthy women was that 41% showed strong enhanced axillary LNs. The dynamic curves of these LNs revealed an initial mean signal increase of 197% (±58%), all of them with a following plateau (34%) or washout (66%). Our study points out that the previous understanding of contrast enhancement in breast lesions should be taken with care when assessing axillary LNs. This has to be considered especially in preoperative breast MRI.

First description of MR mammographic findings in the tumor bed after intraoperative radiotherapy (IORT) of breast cancer.

The aim was to investigate changes in the tumor bed on magnetic resonance mammography (MRM) after intraoperative radiotherapy (IORT) and whether they would limit the diagnostic value of posttherapeutic MRM. We retrospectively investigated 36 patients undergoing MRM after IORT (median interval 2.8 years, range 0.4-7.1). Wound cavities with fat necrosis were common after IORT (81%). They were associated with persisting contrast enhancement, i.e., enhancement was mostly seen irrespective of the posttherapeutic interval. It normally presented as rim enhancement and did not cause any diagnostic uncertainty if viewed together with other tissue characteristics. We do not expect a limited diagnostic value of MRM after IORT.