Assessing the malignancy of suspicious breast microcalcifications: the role of contrast enhanced mammography.

PURPOSE: To assess the role of contrast-enhanced mammography (CEM) in predicting the malignancy of breast calcifications. MATERIAL AND METHODS: We retrospectively evaluated patients with suspicious calcifications (BIRADS 4) who underwent CEM and stereotactic vacuum-assisted biopsy (VAB) at our institution. We assessed the sensitivity (SE), specificity (SP), positive predictive value (PPV) and negative predictive value (NPV) of CEM in predicting malignancy of microcalcifications with a 95% confidence interval; we performed an overall analysis and a subgroup analysis stratified into group A-low risk (BIRADS 4a) and group B-medium/high risk (BIRADS 4b-4c). We then evaluated the correlation between enhancement and tumour proliferation index (Ki-67) for all malignant lesions. RESULTS: Data from 182 patients with 184 lesions were collected. Overall the SE of CEM in predicting the malignancy of microcalcifications was 0.70, SP was 0.85, the PPV was 0.82, the NPV was 0.76 and AUC was 0.78. SE in group A was 0.89, SP was 0.89, PPV was 0.57, NPV was 0.98 and AUC was 0.75. SE in group B was 0.68, SP was 0.80, PPV was 0.87, NPV was 0.57 and AUC was 0.75. Among malignant microcalcifications that showed enhancement (N = 52), 61.5% had Ki-67 ≥ 20% and 38.5% had low Ki-67 values. Among the lesions that did not show enhancement (N = 22), 90.9% had Ki-67 < 20% and 9.1% showed high Ki-67 values 20%. CONCLUSIONS: The absence of enhancement can be used as an indicative parameter for the absence of disease in cases of low-suspicious microcalcifications, but not in intermediate-high suspicious ones for which biopsy remains mandatory and can be used to distinguish indolent lesions from more aggressive neoplasms, with consequent reduction of overdiagnosis and overtreatment.

Magnetic Localization of Breast Lesions: A Large-Scale European Evaluation in a National Cancer Institute.

INTRODUCTION: For decades the standard for preoperative breast lesions' localization has been wire localization. In recent years the options for nonwired localization have significantly expanded and include radioactive seeds, radar reflectors, radiofrequency identification tags and magnetic seeds. The aim of our study is to evaluate on a large scale the performance of preoperative magnetic seed localization of nonpalpable breast lesions. MATERIAL AND METHODS: We prospectively collected data on all patients undergoing image-guided magnetic seed localization from September 2019 to December 2022. We analyzed imaging findings, histological results, and type of surgery. The primary outcome was the successful localization rate. Secondary outcomes were the successful placement rate, the ease of percutaneous positioning, the procedural complications, and the reintervention rate. RESULTS: A total of 1123 magnetic seeds were placed in 1084 patients by 4 radiologists under ultrasound (1053) or stereotactic (70) guidance. All seeds were detectable transcutaneously in all breasts sizes and at all depths by 7 surgeons with a success rate of 100%. A total of 97.5% seeds were correctly placed into the target lesions (only 2.5% were dislocated). All radiologists have shown good compliance during the procedure, and there were no complications or safety issues. The reoperation rate was 5.1%. CONCLUSIONS: Image-guided localization with magnetic seeds is an easy, safe, reliable, and effective method for localizing nonpalpable breast lesions. Both radiologists and surgeons agreed that the technology was intuitive to use and that it can be widely applied in preoperative localization in breast units.

Guiding vacuum-assisted biopsy in prone position: digital breast tomosynthesis vs stereotactic.

PURPOSE: To compare the performance of prone digital breast tomosynthesis (DBT)-vacuum-assisted biopsy (VAB) with prone stereotactic-guided VAB (sVAB), focusing on time of procedure, number of expositions, average glandular dose, and complications. METHODS: The institutional review board approved this retrospective study and informed consent was waived. From July 2015 to January 2017, 306 patients with 306 suspicious mammographic findings (BI-RADS ⩾4) underwent mammography-guided biopsy, prone sVAB, or prone DBT-VAB. Student t test, chi-square, and multivariate regression statistics were used. RESULTS: During the study period, 155 prone sVAB procedures in 155 patients (mean age, 56 years; age range, 39-84 years) and 151 DBT-VABs in 151 patients (mean age, 57 years; age range, 33-84 years) were performed. Mean procedure time was shorter with DBT-VAB versus sVAB (14.5 versus 17.4 minutes, respectively; p < 0.001), and fewer images were acquired with DBT-VAB versus sVAB (8 vs 11, respectively; p < 0.001); the average glandular dose was significantly lower in DBT-VAB versus sVAB (11.8 mGy versus 18 mGy, respectively; p < 0.001). There were no differences in the distribution of histologic results (p = 0.74) or breast density (p = 0.09) between the two groups. No major complications were observed in either group. CONCLUSION: Performance of prone DBT-VAB was superior to prone sVAB because it allowed a faster procedure with fewer radiologic expositions and lower radiation dose.

Circulating miRNAs as Novel Non-Invasive Biomarkers to Aid the Early Diagnosis of Suspicious Breast Lesions for Which Biopsy Is Recommended.

In population-based screens, tissue biopsy remains the standard practice for women with imaging that suggests breast cancer. We examined circulating microRNAs as minimally invasive diagnostic biomarkers to discriminate malignant from benign breast lesions. miRNAs were analyzed by OpenArray in a retrospective cohort of plasma samples including 100 patients with malignant (T), 89 benign disease (B), and 99 healthy donors (HD) divided into training and testing sets and a prospective cohort (BABE) of 289 women with suspicious imaging findings who underwent tissue biopsy. miRNAs associated with disease status were identified by univariate analysis and then combined into signatures by multivariate logistic regression models. By combining 16 miRNAs differentially expressed in the T vs. HD comparison, 26 signatures were also able to significantly discriminate T from B disease. Seven of them, involving 5 specific miRNAs (miR-625, miR-423-5p, miR-370-3p, miR-181c, and miR-301b), were statistically validated in the testing set. Among the 7 signatures, the discriminatory performances of 5 were confirmed in the prospective BABE Cohort. This study identified 5 circulating miRNAs that, properly combined, distinguish malignant from benign breast disease in women with a high likelihood of malignancy.

Automated breast ultrasound compared to hand-held ultrasound in surveillance after breast-conserving surgery.

PURPOSE: To investigate the agreement between automated breast ultrasound (ABUS) and hand-held ultrasound (HHUS) in surveillance of women with a history of breast cancer in terms of recurrences or new ipsilateral or contralateral breast cancer. METHODS: The institutional review board approved this retrospective study and informed consent was waived. From April to June 2016, women with dense breasts undergoing annual surveillance with mammography and HHUS after breast-conserving surgery were offered supplemental ABUS (Invenia). HHUS was performed by a breast radiologist and ABUS by a trained technician. Images were reviewed by 2 breast radiologists. A per-patient BI-RADS category was independently assigned in all cases and categories were dichotomized into negative (1, 2, 3) and positive (4, 5). Cohen κ, McNemar, and Wilcoxon statistics were used. Final pathology was used as reference standard for malignant lesions. RESULTS: A total of 154 women (mean age 62±11 years) were enrolled. Time from surgery was a mean of 8±6 years. Cancer prevalence was 4/154 (2.6%). Interreader agreement for ABUS was 1. Intermethod interreader agreement for HHUS and ABUS was substantial for BI-RADS categories (κ = 0.785) and for dichotomic assessment (κ = 0.794). There was no difference in dichotomic assignment between 2 readers (p = 0.5) but a significant difference in assigning BI-RADS categories (p < 0.05). CONCLUSIONS: A substantial agreement resulted between HHUS and ABUS in surveillance of women with a previous history of breast cancer. In particular, ABUS recognized all cancers detected by HHUS and could play a role in first-level surveillance of women at intermediate risk.

Contrast-enhanced mammography in the evaluation of breast calcifications: preliminary experience.

AIM: To evaluate the presence of contrast enhancement at the site of calcifications on contrast-enhanced mammography (CEM) and histopathologic results at vacuum-assisted biopsy (VAB), and to examine the association with lesion size and immunohistochemical characteristics, in order to assess disease aggressiveness in malignant lesions. METHODS: A total of 34 patients with 36 clusters of suspicious calcifications (BI-RADS 4) were investigated with CEM before the scheduled VAB. We evaluated the presence or absence of enhancement, histologic diagnosis, and, in case of malignant lesions, their size and the expression of Ki-67. RESULTS: In our case series, 15/36 (41.7%) lesions were malignant. In 7 cases, contrast enhancement was found at the site of calcifications. Data about size of lesions and immunohistochemical characterization were not available for all malignant cases. In 5 cases with CEM enhancement, all lesions were >5 mm and overexpressing Ki-67 (>20%); in 6 cases with no contrast enhancement, the lesions were <5 mm and with low Ki-67 values (<20%). CONCLUSION: Our preliminary study provides indications on the ability of CEM to recognize neoplasms larger than 5 mm, with high proliferative index (Ki-67 >20%), and frequently human epidermal growth factor receptor 2-positive. Our preliminary results suggest that CEM could detect aggressive malignancies. This could be the starting point for planning further studies with larger numbers of cases, in an attempt to reduce overdiagnosis and consequent overtreatment.

How Does the Display Luminance Level Affect Detectability of Breast Microcalcifications and Spiculated Lesions in Digital Breast Tomosynthesis (DBT) Images?

RATIONALE AND OBJECTIVES: This study evaluates the influence of the calibrated luminance level of medical displays in the detectability of microcalcifications and spiculated lesions in digital breast tomosynthesis images. MATERIALS AND METHODS: Four models of medical displays with calibrated maximum and minimum luminance, respectively, ranging from 500 to 1000 cd/m2 and from 0.5 to 1.0 cd/m2, were investigated. Forty-eight studies were selected by a senior radiologist: 16 with microcalcifications, 16 with spiculated lesions, and 16 without lesions. All images were anonymized and blindly evaluated by one senior and two junior radiologists. For each study, lesion presence or absence and localization statements, interpretative difficulty level, and overall quality were reported. Cohen's kappa statistic was computed between monitors and within or between radiologists to estimate the reproducibility in correctly identifying lesions; for multireader-multicase analysis, the weighted jackknife alternative free-response receiver operating characteristic statistical tool was applied. RESULTS: Intraradiologist reproducibility ranged from 0.75 to 1.00. Interreader as well as reader-truth agreement values were >0.80 and higher with the two 1000 cd/m2 luminance displays than with the lower luminance displays for each radiologist. Performances in the detectability of breast lesions were significantly greater with the 1000 cd/m2 luminance displays when compared to the display with the lowest luminance value (P value <0.001). CONCLUSIONS: Our findings highlight the role of display luminance level on the accuracy of detecting breast lesions.

Performance and role of the breast lesion excision system (BLES) in small clusters of suspicious microcalcifications.

PURPOSE: To assess the diagnostic performance of the BLES as a biopsy tool in patients with ≤ 1 cm clusters of BIRADS 4 microcalcifications, in order to possibly avoid surgical excision in selected patients. MATERIALS: This is a retrospective study of 105 patients undergone to stereotactic breast biopsy with the BLES. It excises a single specimen containing the whole mammographic target, allowing better histological assessment due to preserved architecture. RESULTS: Our case series consists of 41 carcinomas (39%) and 64 benign lesions (61%). Cancer involved the specimen margins in 20/41 cases (48.8%) or was close to them (≤ 1 mm) in 14 cases (34.1%); margins were disease-free in only 7 DCIS (17.1%). At subsequent excision of 39/41 malignant cases, underestimation occurred for 5/32 DCIS (15.6%), residual disease was found in 15/39 cancers (38.5%) and no cancer in 19/39 cases (48.7%). For DCIS cases, no residual disease occurred for 66.7% G1-G2 cases and for 35.3% G3 cases (P=0.1556) as well as in 83.3%, 40.0% and 43.8% cases respectively for negative, close and positive BLES margins (P=0.2576). CONCLUSIONS: The BLES is a good option for removal of small clusters of breast microcalcifications, giving better histological interpretation, lower underestimation rates and possibly reducing the need of subsequent surgical excision in selected patients.

Mammographic findings after reshaping with autoprosthesis in women undergoing contralateral breast reconstruction and mastectomy.

AIMS AND BACKGROUND: Breast reduction and mastopexy combined with inferior dermo-lipo-glandular flap (autoprosthesis) gives good breast shape, long-term projection, and upper pole fullness. We assess the impact on breast oncologic surveillance compared to other techniques. METHODS: A total of 105 patients who underwent mastectomy and reconstruction were divided into 3 groups of 35 patients each: groups 1 and 2 include patients with contralateral breast symmetrization performed with and without autoprosthesis technique, respectively. Group 3 is a control group without contralateral breast reshaping. On mammography, edema, skin thickening, architectural distortion, and calcifications were recorded, as well as further diagnostic examinations, biopsies, and surgical treatments required. RESULTS: Statistically significant differences (p<0.001) in the first follow-up mammography between groups 1 and 2 were stromal edema (6% vs 51%) and architectural distortion (74% vs 63%). The latest findings meant architectural distortion also have significant difference (p<0.001) in the last mammography (79% vs 66%). Microcalcification has statistically significant difference (p<0.001) in the latest postsurgical mammography, increased in group 1. Skin thickening had a similar course in either group. Mammography follow-up was not impaired in most cases notwithstanding the parenchyma distortion as compared with mammography after breast-conserving surgery. Four core biopsies were performed in both groups: 3 new breast cancers and 1 benign epithelial hyperplasia were found. CONCLUSIONS: No difficulties were found impairing mammographic evaluation in patients treated with autoprosthesis as compared to other techniques.

Has color Doppler a role in the evaluation of mammary lesions?

Has color Doppler a role in the evaluation of mammary lesions? A schematic review of color Doppler diagnostic criteria, indicating a benign or malignant lesion, are described.Malignant tumors have a tendency to show increased vascularization, but avascular tumors may be found as well as hypervascular benign tumors.Number of vessels, blood-flow velocity, and intra-tumoral vessel resistance assessed by color Doppler ultrasonography don't permit clear differentiation between malignant and benign tumors, but intra-tumoral blood-flow analysis well correlates with aggressiveness and histological grade of the mass, so a preoperative assessment using Color Doppler may give preliminary prognostic informations useful for therapeutic planning.Color Doppler ultrasound may be valuable also in assessing the efficacy of neoadjuvant chemotherapy and in particular of antiangiogenesis treatments.Color Doppler ultrasound has many other useful applications in the evaluation of diseases of the female and male breast, that are reviewed in the paper.Color Doppler however is not conceived as a stand-alone examination, but associated with B-mode ultrasound that is quite effective as a diagnostic tool, often not requiring Doppler informations.

Role of sonoelastography in non-palpable breast lesions.

The purpose of this study was to evaluate the diagnostic utility of sonoelastography in differentiating benign from malignant non-palpable breast lesions. A total of 293 BI-RADS 3-5 (Breast Imaging Reporting And Data System) impalpable breast lesions in 278 women was evaluated with B-mode ultrasound (US) and subsequently with sonoelastography (SE) before performing US-guided biopsy. Among the 293 lesions (size up to 2 cm), 110 (37.5%) were histologically malignant and 183 (62.5%) benign. Lesions that were malignant or showed atypical ductal hyperplasia were referred for surgical excision, as well as 32 benign lesions showing discordance between US/SE results and histology. All other benign lesions had US follow-up at 6/12 months, showing stability. Overall performance of SE was lower than US, with sensitivity and specificity of 80% and 80.9%, respectively, for SE as compared with 95.4% and 87.4% for US. Statistical analysis showed no improvement in the joint use of SE and US over the use of US alone, whose performance, however, was very high in our study. SE is a simple, fast and non-invasive diagnostic method that may be a useful aid to US for less experienced radiologists in the assessment of solid non-palpable breast lesions, especially BI-RADS 3, where specificity was higher (88.7%).

MRI in the early detection of breast cancer in women with high genetic risk.

AIMS AND BACKGROUND: Women with BRCA1 or BRCA2 germline mutations have an elevated risk of developing breast and/or ovarian cancer. Because of the early onset of the disease, screening of this group of women should start at an earlier age than in the general population. The association of breast magnetic resonance imaging (BMRI) and ultrasonography (US) with mammography (MX) and clinical breast examination (CBE) in the regular surveillance of these individuals has been proposed and seems to improve the early detection of breast cancer. METHODS: Within a multicenter study started by the Istituto Superiore di Sanità (Rome), at the Istituto Nazionale Tumori of Milan (INT) we enrolled 116 women at high genetic risk for breast cancer; they were either BRCA1 or BRCA2 mutation carriers or had a strong family history of breast cancer. They underwent CBE, MX, US and BMRI once a year. RESULTS: Between June 2000 and April 2005, at INT 12 cancers were detected among the 116 screened individuals (10%). In this subgroup, 1 patient refused BMRI and in 2 cases US was not performed. With BMRI we found 11 cancers and 6 of them were detectable only by this technique. In these 6 cases, the size of the disease was less than 1 cm and MX was false negative due to irregularly nodular parenchyma in 4 cases and scar tissue or prosthesis in the other 2. US was not performed in 2 cases and was false negative in 4 cases. Three false positive results were found with BMRI: 1 case was considered suspect but related to hormonal influences; 1 case with the same pattern was sent for second-look US, which gave a negative result and BMRI review after 6 months showed normalization of the parenchyma; in the third case histology revealed the presence of adenosis. No false positive results were registered for MX. CONCLUSIONS: The aim of secondary prevention is the detection of cancer at its earliest stage. BMRI screening in women with BRCA1 or BRCA2 mutations or at high familiar risk appears to be highly sensitive and may detect mammographically occult disease. The accuracy of MR imaging is higher than that of conventional imaging but the technique is flawed by a lower specificity. In order to avoid unnecessary biopsies we believe that the combination of BMRI and conventional imaging can be very useful in screening women with a high genetic risk of breast cancer, especially with second-look evaluation by means of US when BMRI yields the only positive diagnostic result. Second-look US has been demonstrated to be of critical importance both in recognizing false positive BMRI results and in guiding biopsies, when necessary.