Comparing the diagnostic accuracy, reading time, and inter-rater agreement of breast MRI abbreviated and full protocols: a multi-reader study.

BACKGROUND: Earlier studies have shown that abbreviated protocol magnetic resonance imaging (AB-MRI) has similar diagnostic accuracy as the full protocol (Full MRI). PURPOSE: To compare the diagnostic accuracy, reading time, and inter-rater agreement of AB-MRI to Full MRI among women without known increased familial risk of breast cancer or prior biopsy. MATERIAL AND METHODS: In total, 395 MRI examinations were included in this study. Three readers were blinded to all patient information. The AB-MRI and Full MRI were read separately and in a different random order for each of the readers. Scores 1-2 were considered test negative while scores 3-5 were test positive. A positive reference test was the diagnosis of malignancy; a negative reference test was the absence of a diagnosis of breast cancer within a two-year follow-up. We used a generalized estimating equations approach to compare sensitivity and specificity between the two protocols. We used t-tests to compare the average reading time and Krippendorff's alpha to compare inter-rater agreement. RESULTS: MRI examinations of 395 women (median age=56 years) were evaluated. For AB-MRI and Full MRI, respectively, the sensitivity was 93.0% (95% CI=90.6-95.0) vs. 92.0% (95% CI=89.4-94.1), the specificity was 91.7% (95% CI=90.3-92.9) vs. 94.3% (95% CI=93.2-95.3), average reading time was 67 vs. 126 s, and the inter-rater agreement 0.79 vs. 0.83. The difference in sensitivity was not statistically significant (P=0.840), but the difference in specificity was significant (P=0.003). CONCLUSION: AB-MRI has similar sensitivity, but somewhat lower specificity. The average reading time for the abbreviated protocol is lower, as is inter-rater agreement.

The association between breast cancer risk factors and background parenchymal enhancement at dynamic contrast-enhanced breast MRI.

BACKGROUND: Background parenchymal enhancement (BPE) of normal tissue at breast magnetic resonance imaging is suggested to be an independent risk factor for breast cancer. Its association with established risk factors for breast cancer is not fully investigated. PURPOSE: To study the association between BPE and risk factors for breast cancer in a healthy, non-high-risk screening population. MATERIAL AND METHODS: We measured BPE and mammographic density and used data from self-reported questionnaires in 214 healthy women aged 43-74 years. We estimated odds ratios for the univariable association between BPE and risk factors. We then fitted an adjusted model using logistic regression to evaluate associations between BPE (high vs. low) and risk factors, including mammographic breast density. RESULTS: The majority of women had low BPE (84%). In a multivariable model, we found statistically significant associations between BPE and age (P = 0.002) and BMI (P = 0.03). We did find a significant association between systemic progesterone medication and BPE, but due to small numbers, the results should be interpreted with caution. The adjusted odds ratio for high BPE was 3.1 among women with density D (compared to B) and 2.1 for density C (compared to B). However, the association between high BPE and density was not statistically significant. We did not find statistically significant associations with any other risk factors. CONCLUSION: Our study confirmed the known association of BPE with age and BMI. Although our results show a higher likelihood for high BPE with increasing levels of mammographic density, the association was not statistically significant.

Assessment of early response biomarkers in relation to long-term survival in patients with HER2-negative breast cancer receiving neoadjuvant chemotherapy plus bevacizumab: Results from the Phase II PROMIX trial.

Pathologic complete response (pCR) is a predictor for favorable outcome after neoadjuvant treatment in early breast cancer. Modulation of gene expression may also provide early readouts of biological activity and prognosis, offering the possibility for timely response-guided treatment adjustment. The role of early transcriptional changes in predicting response to neoadjuvant chemotherapy plus bevacizumab was investigated. One-hundred-and-fifty patients with large, operable and locally advanced HER2-negative breast cancer received epirubicin and docetaxel, with the addition of bevacizumab. Patients underwent tumor biopsies at baseline, after Cycle 2 and at the time of surgery. The primary end point, pCR, and its relation with the secondary endpoints event-free survival (EFS), overall survival (OS) and gene expression profiles, are reported. The pCR rate was 13% (95% CI 8.6-20.2), with significantly more pCRs among triple-negative [28% (95% CI 14.8-45.4)] than among hormone receptor positive (HR+) tumors [9% (95% CI 4.6-16.3); (OR = 3.9 [CI = 1.5-10.3])]. pCR rates were not associated with EFS or OS. PAM50 subtypes significantly changed after Cycle 2 (p = 0.03) and an index of absolute changes in PAM50 correlations between these time-points was associated with EFS [HR = 0.62 (CI = 0.3-1.1)]. In univariable analyses, signatures for angiogenesis, proliferation, estrogen receptor signaling, invasion and metastasis, and immune response, measured after Cycle 2, were associated with pCR in HR+ tumors. Evaluation of changes in molecular subtypes and other signatures early in the course of neoadjuvant treatment may be predictive of pCR and EFS. These factors may help guide further treatment and should be considered when designing neoadjuvant trials.

Contrast-enhanced ultrasound (CEUS) in assessing early response among patients with invasive breast cancer undergoing neoadjuvant chemotherapy.

Background One of the big challenges in onco-radiology is to find a reliable imaging method that may predict early response during the first cycles of any neoadjuvant chemotherapy. Purpose To evaluate the use of real-time harmonic contrast-enhanced ultrasound (CEUS) in predicting early response in breast cancer tumors under neoadjuvant chemotherapy (NAC) treatment. Material and Methods Nineteen consecutive patients with invasive breast cancer were evaluated with a bolus dose of 2.4 mL contrast agent using CEUS, before and after two cycles of epirubicin and docetaxel. The lognormal function was used for quantitative analysis of kinetic data to evaluate early response. Results There was statistically significant difference in time-to-peak ( tp) between responders and non-responders (two sample t-test, P = 0.027) where tp was significantly longer at the week 5 than at the baseline scan among responders when compared to non-responders. Conclusion In-flow of intravascular contrast agent in tumors is significantly slower in responders at real-time harmonic CEUS, and might be effectively used for the evaluation of early response to chemotherapy in invasive breast cancer. However, further investigations in a larger and more heterogeneous population should be performed to corroborate the reliability of the method.

Comparison of handheld ultrasound and automated breast ultrasound in women recalled after mammography screening.

Background Automated breast volume scanner (ABVS) is an ultrasound (US) device with a wide scanner that sweeps over a large area of the breast and the acquired transverse images are sent to a workstation for reconstruction and review. Whether ABVS is as reliable as handheld US is, however, still not established. Purpose To compare the sensitivity and specificity of ABVS to handheld breast US for detection of breast cancer, in the situation of recall after mammography screening. Material and Methods A total of 113 women, five with bilateral suspicious findings, undergoing handheld breast US due to a suspicious mammographic finding in screening, underwent additional ABVS. The methods were assessed for each breast and each detected lesion separately and classified into two categories: breasts with mammographic suspicion of malignancy and breasts with a negative mammogram. Results Twenty-six cancers were found in 25 women. In the category of breasts with a suspicious mammographic finding (n = 118), the sensitivity of both handheld US and ABVS was 88% (22/25). The specificity of handheld US was 93.5% (87/93) and ABVS was 89.2% (83/93). In the category of breasts with a negative mammography (n = 103), the sensitivity of handheld US and ABVS was 100% (1/1). The specificity of handheld US was 100% (102/102) and ABVS was 94.1% (96/102). Conclusion ABVS can potentially replace handheld US in the investigation of women recalled from mammography screening due to a suspicious finding. Due to the small size of our study population, further investigation with larger study populations is necessary before the implementation of such practice.

Contrast-enhanced ultrasound using real-time contrast harmonic imaging in invasive breast cancer: comparison of enhancement dynamics with three different doses of contrast agent.

BACKGROUND: In the last few years new potential applications have been developed for contrast-enhanced ultrasound (CEUS) and the management of breast diseases, but there is still some debate concerning the optimal dose to evaluate breast lesions, especially as a diagnostic tool. PURPOSE: To compare different CEUS doses of injected contrast agent in order to establish an optimal dose for the diagnosis of invasive breast cancer. MATERIAL AND METHODS: In Group A we compared the bolus dose of 1.2 mL vs. 2.4 mL and in Group B we compared the bolus dose of 2.4 mL vs. 4.8 mL (26 and 25 invasive carcinomas, respectively). CEUS was performed in real-time contrast harmonic imaging (CHI) using a L9-3 MHz probe. All examinations were recorded in a contrast side/side imaging mode loop for 120 s. Wash-in and wash-out patterns of the contrast agent were analyzed with advanced US quantification software and kinetic curves were used for statistical analysis. RESULTS: In Group B (2.4 mL vs. 4.8 mL), more and stronger correlation was found among kinetic parameters (area under the curve, P < 0.00001; lognormal model parameters, µ, P = 0.0007 and σ, P < 0.0001; mean transit time, P < 0.0001; model-based wash-out ratios, W21m, P = 0.0002; W50m, P = 0.0001; time-to-peak, P = 0.005) as compared to Group A (1.2 mL vs. 2.4 mL). CONCLUSION: The optimal way to evaluate kinetic features of invasive breast tumors using real-time CEUS is with an injection of contrast agent of either 2.4 mL or 4.8 mL.

Correlation of contrast-enhanced ultrasound kinetics with prognostic factors in invasive breast cancer.

OBJECTIVES: To correlate contrast-enhanced ultrasound (CEUS) kinetic parameters with traditional and molecular prognostic factors in invasive breast cancer. METHODS: Seventy-five invasive breast cancers were evaluated with contrast harmonic imaging after the injection of a bolus dose of 2.4 ml sulphur hexafluoride microbubble contrast agent. The lognormal function was used for quantitative analysis of kinetic data. These parameters correlated with traditional prognostic factors (tumour size, histological type, tumour grade, axillary lymph node status) and immunohistochemical biomarkers (ER, PR and HER2 status). RESULTS: Statistically significant correlation was found between time-to-peak and tumour grade (P value = 0.023), PR status (P value = 0.042) and axillary node status (P value = 0.025). Wash-out ratio, measured at 21 s was significantly associated with ER status (P value = 0.042) and PR status (P value = 0.026). CONCLUSIONS: Invasive breast carcinomas exhibiting earlier peak enhancement and faster elimination of microbubble contrast agent at CEUS are found to be associated with established predictors of poor prognosis.

Differentiation between benign and malignant breast tumors using kinetic features of real-time harmonic contrast-enhanced ultrasound.

BACKGROUND: Contrast-enhanced ultrasound (CEUS) has gained interest because of its ability to gather vascular information in diverse organs. There is still a subject of debate concerning its value in breast lesions, especially as a differential diagnostic tool. PURPOSE: To investigate whether kinetic parameters of CEUS can differentiate between malignant and benign breast lesions. MATERIAL AND METHODS: We evaluated 75 malignant and 21 benign lesions in the breast or axilla. Contrast harmonic imaging (CHI) US was performed after the injection of a bolus dose of 2.4 mL of Sono Vue® (Bracco, Milano, Italy). The following parameters were calculated for kinetic analysis: initial slope, time to peak enhancement, wash-out ratios W(21) and W(50) (relative decrease in signal intensity from the peak enhancement to 21 s and 50 s, respectively). RESULTS: A significant difference was found between the benign and malignant lesions in time-to-peak (P value <0.05) and wash-out ratios W(21) (P value <0.001) and W(50) (P value <0.001). The mean time-to-peak was 9.3 s for malignant and 14.6 s for benign lesions. The mean signal drop from peak to signal intensity measured at 50 s was 85% for malignant and 66% for benign lesions. There was no difference in absolute values of peak signal intensity and initial slope. The most significant difference between standardized benign and malignant wash-out curves was found at 21 s but statistical significance was reached in the range of 14-50 s. CONCLUSION: Real-time CEUS can evolve into a new non-invasive option for differentiate malignant from benign breast lesions.

High velocity pulse biopsy device enables controllable and precise needle insertion and high yield tissue acquisition.

Minimally invasive biopsies are a cornerstone of breast cancer management with ultrasound being the preferred guidance modality. New developments in breast cancer management and advances in imaging technologies bring new challenges to current biopsy methodologies. A new biopsy device (NeoNavia® biopsy system, 14 G) was developed. It incorporates a pneumatic needle insertion mechanism that is intended to provide better control of needle progression and enable stepwise insertion without noticeable deformation or displacement of surrounding tissue as visualized under ultrasound. A new method of tissue acquisition was designed to achieve a sampling yield higher than standard methodologies. Needle dynamics was assessed on a specifically designed test bed and sampling performance was compared to a Magnum® biopsy instrument (Bard, Covington, GA, USA) in representative tissue models. The histological quality of samples obtained ex-vivo was evaluated. A pneumatic pulse was measured to accelerate the needle to a maximum velocity of 21.2 ±â€¯2.5 m/s on a stroke length of 2.5 mm, achieving significantly higher acceleration, maximum velocity and power than current biopsy devices. Mean weight of samples obtained by the NeoNavia device were 3.5, 4.6, and 4.3 times higher when sampling was performed in turkey breast, calf thymus and swine pancreas, respectively, as compared to samples obtained with the Magnum instrument. Ex-vivo analysis indicates that the method of tissue acquisition has no apparent negative impact on the histopathologic quality of obtained samples.

Integrin receptor imaging of breast cancer: a proof-of-concept study to evaluate 99mTc-NC100692.

UNLABELLED: The present study was a proof-of-concept study to provide an initial indication of the efficacy and safety of imaging malignant breast tumors using (99m)Tc-NC100692. The agent is a small peptide with high affinity for integrin receptors that are upregulated and expressed preferentially on proliferating endothelial cells. METHODS: Sixteen patients with suggestive mammographic findings and 4 patients with benign lesions were included. The "standard of truth" was based on the histopathologic diagnosis of the recruited patients. All subjects received up to 75 microg of (99m)Tc-NC100692 with an average (99m)Tc activity of 694 MBq (range, 561-747 MBq). Safety endpoints were treatment-emergent adverse events (AEs) and changes in a limited physical examination, electrocardiogram (ECG) recordings, blood biochemistry, hematology, coagulation, vital signs, and urine analysis after administration of (99m)Tc-NC100692 and throughout the 24-h follow-up. Static images and SPECT were acquired between 40 min and 2.5 h after injection of the agent. Two experienced nuclear medicine physicians read the images in a nonblinded fashion. RESULTS: Nineteen of 22 malignant lesions were detected using (99m)Tc-NC100692 scintigraphy. Twenty lesions confirmed as malignant by histopathology were seen on mammography or ultrasound. Two additional lesions were identified from histopathology alone. Safety parameters evaluated through the follow-up period of 2.5 h included clinical laboratory tests, vital signs, and ECG. Five of 20 subjects experienced nonserious AEs, and all AEs were classified as mild. One subject experienced an AE (dysgeusia) possibly related to administration of (99m)Tc-NC100692. This AE was mild and lasted only for a few minutes. No deaths, serious AEs, or withdrawals due to AEs occurred during the study. CONCLUSION: Nineteen of 22 malignant lesions (86%) were clearly detected via scintigraphic imaging after administration of (99m)Tc-NC100692. Overall, the efficacy data in subjects with suspected breast lesions suggest that (99m)Tc-NC100692 scintigraphy may be effective in detecting malignant lesions. The use of (99m)Tc-NC100692 in subjects with breast cancer is safe and well tolerated. Further studies are warranted to assess the clinical potential of (99m)Tc-NC100692.

Feasibility study on the treatment of small breast carcinoma using percutaneous US-guided preferential radiofrequency ablation (PRFA).

The purpose of this study was to determine the safety and efficacy of percutaneous ultrasound (US) guided preferential radiofrequency ablation (PRFA) of unifocal human invasive breast carcinoma with largest radiological diameters of up to 16 mm. Thirty-three patients were enrolled in a study to be treated prior to scheduled partial mastectomy. A needle-shaped treatment electrode, successively developed in two different sizes, was placed into the center of the lesions using ultrasound guidance. A temperature of 85 degrees C was maintained for 10 min. The analysis of the resected specimen was performed using conventional histopathological methods with the aim to determine the size of the lesion as well as the potential viability of tumor cells. Of the 33 patients enrolled 31 were treated. In 26 (84%) patients a complete ablation of the tumor was achieved. Ultrasound guided preferential radiofrequency ablation of small breast carcinoma is feasible and patient friendly. The success rate depends on accurate preoperative diagnostic imaging as well as an exact position of the needle electrode.