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.

Adding 3D automated breast ultrasound to mammography screening in women with heterogeneously and extremely dense breasts: Report from a hospital-based, high-volume, single-center breast cancer screening program.

PURPOSE: The aim of this study was to evaluate the impact of the 3D automated breast ultrasound (3D ABUS) when added to full field digital screening mammography (FFDSM), on breast cancer detection and recall rates in asymptomatic women with dense breasts examined in a high-volume breast cancer screening mammography center. METHODS AND MATERIAL: 1668 asymptomatic women, age 40-74 years, with heterogeneously dense parenchyma (ACR3) or extremely dense breast (ACR4) were included in the study. FFDSM was performed using standard craniocaudal (CC) and mediolateral oblique (MLO) views followed by anteroposterior (AP); lateral (LAT) and medial (MED) acquisitions of 3D ABUS in both breasts. All mammograms were double read by two dedicated breast radiologists. The 3D ABUS was read by the first radiologist immediately after reading the mammograms. The second reader looked at the 3D ABUS only if there was a need for consensus discussion because of unclear or abnormal mammograms or 3D ABUS. RESULTS: The combined FFDSM and 3D ABUS generated a total of 6.6 cancers per 1000 women screened (95% CI: 3.0, 10.2; p<0.001) compared with 4.2 cancers per 1000 women screened (95% CI) for FFDSM alone. The difference in yield was an additional 2.4 detected cancers per 1000 women screened (95% CI: 0.6, 4.8; p<0.001). The corresponding recall rate per 1000 women screened was 13.8 (95% CI: 9.0, 19.8) for FFDSM alone and 22.8 for combined FFDSM and ABUS (95% CI: 16.2, 30.0), yielding a difference of an additional 9.0 recalls per 1000 women screened (95% CI: 3.0, 15.0; p=0.004). CONCLUSION: The addition of 3D ABUS to FFDSM in women with ACR3 or ACR4 breast density significantly improved invasive breast cancer detection rate with an acceptable recall increase.

Imaging surveillance programs for women at high breast cancer risk in Europe: Are women from ethnic minority groups adequately included? (Review).

Women from ethnic minority groups, including immigrants and refugees are reported to have low breast cancer (BC) screening rates. Active, culturally-sensitive outreach is vital for increasing participation of these women in BC screening programs. Women at high BC risk and who belong to an ethnic minority group are of special concern. Such women could benefit from ongoing trials aimed at optimizing screening strategies for early BC detection among those at increased BC risk. Considering the marked disparities in BC survival in Europe and its enormous and dynamic ethnic diversity, these issues are extremely timely for Europe. We systematically reviewed the literature concerning European surveillance studies that had imaging in the protocol and that targeted women at high BC risk. The aim of the present review was thereby to assess the likelihood that women at high BC risk from minority ethnic groups were adequately included in these surveillance programs. Twenty-seven research groups in Europe reported on their imaging surveillance programs for women at increased BC risk. The benefit of strategies such as inclusion of magnetic resonance imaging and/or more intensive screening was clearly documented for the participating women at increased BC risk. However, none of the reports indicated that sufficient outreach was performed to ensure that women at increased BC risk from minority ethnic groups were adequately included in these surveillance programs. On the basis of this systematic review, we conclude that the specific screening needs of ethnic minority women at increased BC risk have not yet been met in Europe. Active, culturally-sensitive outreach is needed to identify minority women at increased BC risk and to facilitate their inclusion in on-going surveillance programs. It is anticipated that these efforts would be most effective if coordinated with the development of European-wide, population-based approaches to BC screening.

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.

Effects of short-term estradiol and norethindrone acetate treatment on the breasts of normal postmenopausal women.

OBJECTIVE: The aim of this study was to evaluate among postmenopausal women the effects of a 3-month treatment with estradiol (E2) alone or in combination with norethindrone acetate (NA) on expression of hormone receptors and proliferation in the breast as well as on lipids and climacteric symptoms. METHODS: Sixty healthy postmenopausal women were computer-randomized into two groups, with one group receiving 1 mg of E2 and the other group receiving 1 mg of E2 and 0.5 mg of NA daily for 12 weeks. Before and after treatment, middle-needle biopsies were obtained for histology and investigation of the expression levels of estrogen receptors (ERs; ER-α and ER-ß), progesterone receptors (PRs; PR-A and PR-B), androgen receptor (AR), the proliferation marker Ki67, and collagen. Climacteric symptoms were recorded, and serum was collected to measure lipoprotein levels. RESULTS: Fifty-six women finished the 12-week study. Proliferating cells (Ki67-positive) were very rare in all but a few of the untreated women. There were proliferating cells in both E2- and E2/NA-treated groups; however, these were not widespread and limited to nests of cells that amounted to 2% of the total epithelial cells. Some of these nests were positive for human epithelial growth factor receptor 2. Treatments caused no marked changes in the expression of ER-α, ER-ß, or AR. However, both treatments resulted in an increase in PR-A and PR-B expressions. The presence of collagen was clearly associated with a mammographic diagnosis of dense breasts, but neither hormone treatment affected breast density. Both E2 and E2/NA treatments were effective in relieving hot flashes and sweating without adverse effects on blood pressure, weight, and liver, kidney, and thyroid functions. A decrease in cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol was induced by E2/NA but not by E2. CONCLUSIONS: This short-term prospective study shows that E2 and estrogen-progestogen treatment can up-regulate PRs but do not significantly affect ERs, AR, proliferation, or breast density.

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.

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.

Isoflavone treatment for acute menopausal symptoms.

OBJECTIVE: The onset of climacteric symptoms (hot flashes and night sweats) is the primary reason for perimenopausal women to start hormone therapy. The association of a lower incidence of postmenopausal symptoms with high intake of soybeans in Asian women suggests that phytoestrogens are an alternative to estrogen therapy. The main effective compounds in soybean are isoflavones, which have a higher binding affinity to estrogen receptor beta than to estrogen receptor alpha. The aim of present study was to evaluate the effects of isoflavone treatment in postmenopausal women. DESIGN: This was a double-blind prospective study. Sixty healthy postmenopausal women were randomly assigned by computer into two groups to receive 60 mg isoflavones or placebo daily for 3 months. Before and after treatment, climacteric symptoms were recorded; serum was collected to measure the levels of lipoprotein lipids, estradiol, and follicle-stimulating hormone; and biopsy specimens from endometrium and breast were analyzed to investigate the expression level of steroid receptors and proliferation. Endometrial thickness was measured by ultrasound. RESULTS: Fifty-one women finished the 12-week study. In women receiving 60 mg isoflavones daily, hot flashes and night sweats were reduced by 57% and 43%, respectively. The treatment did not change the levels of circulating estradiol or follicle-stimulating hormone. Immunohistochemical staining of endometrial and breast biopsy specimens revealed that isoflavones did not affect expression levels of steroid receptors; estrogen receptors alpha, beta, and betacx; progesterone receptors A and B; or the proliferation marker Ki67. No side effects on body weight or lipoprotein lipids were observed. CONCLUSIONS: This short-term prospective study implies that isoflavones could be used to relieve acute menopausal symptoms.

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.

Different methods for the detection of small changes in uptake between single-photon emission computed tomography (SPECT) examinations: 99mTc-sestamibi in chemotherapy for breast tumours.

AIM: This study was undertaken to evaluate different methods for the detection of small changes in uptake between single-photon emission computed tomography (SPECT) examinations in the same individual. No standard exists for making digital evaluations at single-photon examinations. For this purpose, we employed a patient cohort from a previous study assessing the response to neoadjuvant chemotherapy for breast cancer using Tc-hexakis-2-methoxyisobutylisonitrile (Tc-sestamibi). METHODS: The tumour uptake in 29 women with locally advanced breast cancer was examined using Tc-sestamibi and SPECT before neoadjuvant chemotherapy and, on average, 19 days after one chemotherapy cycle. The histology of the finally resected tumour confirmed a therapeutic response. Different assessments of the uptake, various levels of background activity subtraction and different reference tissues for relative activity calculations were used. The tumour uptake and activity of the reference tissues were also related to the administered activity. RESULTS: Different definitions of tumour activity had little influence. Relating the tumour uptake to a large portion of the abdomen, as well as visual evaluation, showed a therapeutic response. Comparison with the administered activity showed that the apparent responses were due to an increased activity of the reference tissues. Referring the tumour uptake to the administered activity truly depicted a therapeutic response. CONCLUSIONS: A critical attitude is necessary when making digital evaluations at SPECT. Digital data may seem more relevant than they really are. Relative comparisons may be unreliable. It may be necessary to develop standardized methods for this purpose.

99mTc-exametazime as a breast tumor-seeking agent: comparison with 99mTc-sestamibi.

UNLABELLED: (99m)Tc-sestamibi is commonly used for mammoscintigraphy. Occasional uptake of (99m)Tc-exametazime in various tumors has been described. In this study, an intraindividual comparison of these 2 radiopharmaceuticals for mammoscintigraphy was made. METHODS: A kinetic study (30 min) in the lateral prone view of 20 breast tumors (> or =1 cm) in 20 women was conducted with (99m)Tc-exametazime. Thereafter, 21 breast tumors (> or =1 cm) in 21 women were examined with both agents (2 patients were included in both groups) under identical conditions (interval, 2-7 d). In the latter group, the tumor-to-background breast activity ratio and the tumor uptake normalized to the administered activity (cps/MBq) at 10 min after injection were calculated and compared for both agents. RESULTS: All tumors (43 tumors in 39 patients) were visualized with (99m)Tc-exametazime. There was also one instance of false-positive uptake using this agent. The uptake phase lasted approximately 10 min. Thereafter, the activity was practically stable. (99m)Tc-Sestamibi failed to depict 4 tumors. On the group level, the tracers did not differ in tumor-to-background activity ratio or normalized tumor uptake. Intraindividual agreement in tumor-to-background ratios between the tracers was moderate (intraclass correlation coefficient = 0.49). CONCLUSION: Uptake of (99m)Tc-exametazime in breast tumors > or = 1 cm seems to be comparable with that of (99m)Tc-sestamibi at a group level. The specificity is unknown. There is a restricted intraindividual agreement between the tracers, confirming different uptake mechanisms. This may open up possibilities for assessing different tumor characteristics in vivo, especially since the uptake of both agents is based on mechanisms believed to be involved in resistance to antineoplastic drugs.

Sentinel node scintigraphy in breast cancer using a dual tracer technique.

AIM: In order to depict the anatomy and improve the localization, sentinel node scintigraphy in breast cancer was combined with intravenous administration of pertechnetate. As this may reduce the detectability of weak 'hot spots', the number of lymph nodes detected at scintigraphy and at surgery in one group of patients was compared with that obtained in another group that had not received pertechnetate. PATIENTS AND METHODS: The number of 'hot spots' at frontal and lateral views in 47 female patients at scintigraphy performed 2-3 h after subcutaneous injection of radiocolloid together with 25 MBq pertechnetate i.v. was compared in retrospect with that of 41 female patients who had not received pertechnetate. The number of lymph nodes detected at surgery using a hand-held gamma probe together with blue dye in the two groups was also compared. The washout kinetics of pertechnetate was studied in 10 patients. RESULTS: There was no difference in the number of detected lymph nodes at any comparison. The kinetics study revealed a decreasing activity with time after correction for physical decay. CONCLUSION: Administration of a 25 MBq pertechnetate i.v. in order to improve the anatomical localization at sentinel node scintigraphy in breast cancer does not reduce the detectability of radioactive lymph nodes.