Deciphering clinical significance of BCL11A isoforms and protein expression roles in triple-negative breast cancer subtype.

PURPOSE: Triple negative breast cancer (TNBC) is an aggressive clinical tumor, accounting for about 25% of breast cancer (BC) related deaths. Chemotherapy is the only therapeutic option to treat TNBC, hence a detailed understanding of the biology and its categorization is required. To investigate the clinical relevance of BCL11A in TNBC subtype, we focused on gene and protein expression and its mutational status in a large cohort of this molecular subtype. METHODS: Gene expression profiling of BCL11A and its isoforms (BCL11A-XL, BCL11A-L and BCL11A-S) has been determined in Luminal A, Luminal B, HER2-enriched and TNBC subtypes. BCL11A protein expression has been analyzed by immunohistochemistry (IHC) and its mutational status by Sanger sequencing. RESULTS: In our study, BCL11A was significantly overexpressed in TNBC both at transcriptional and translational levels compared to other BC molecular subtypes. A total of 404 TNBCs were selected and examined showing a high prevalence of BCL11A-XL (37.3%) and BCL11A-L (31.4%) isoform expression in TNBC, associated with a 26% of BCL11A protein expression levels. BCL11A protein expression predicts scarce LIV (HR = 0.52; 95% CI, 0.29-0.92, P = 0.03) and AR downregulation (HR = 0.37; 95% CI, 0.16-0.88; P = 0.02), as well as a higher proliferative index in TNBC cells. BCL11A-L expression is associated with more aggressive TNBC histological types, such as medullary and metaplastic carcinoma. CONCLUSION: Our finding showed that BCL11A protein expression acts as an unfavorable prognostic factor in TNBC patients, especially in non luminal TNBCs subgroups. These results may yield a better treatment strategy by providing a new parameter for TNBC classification.

Scintimammography with dedicated breast camera in unifocal and multifocal/multicentric primary breast cancer detection: a comparative study with SPECT.

The aim of this study was to assess the usefulness of planar scintimammography (SM) with a high-resolution dedicated breast camera (DBC) compared to SPECT in unifocal and multifocal/multicentric primary breast cancer (BC) detection. DBC planar SM and conventional SPECT were acquired using 99mTc-tetrofosmin as radiotracer in 85 consecutive patients suspect for BC at conventional imaging and clinical examination. Scintigraphic data were related to histology in all cases. BC was proven in 74/85 patients, unifocal in 56/74 cases and multifocal/multicentric in 18/74; 90 carcinomas were ascertained. Benign lesions were found in 12 cases, including one who also had BC in the contralateral breast. DBC planar SM and SPECT were true-positive in 72/74 and in 70/74 BC patients, respectively, and globally detected 96.7% and 92.2% of carcinomas. DBC and SPECT sensitivity were, respectively, 90.3% and 80.6% in

Breast cancer axillary lymph node metastasis detection by a high-resolution dedicated breast camera: a comparative study with SPECT and pinhole SPECT.

We evaluated the usefulness of (99m)Tc-tetrofosmin planar scintigraphy acquired with a high-resolution (HR) dedicated breast camera in comparison with conventional single-photon emission computed tomography (SPECT) and pinhole-SPECT (P-SPECT) in breast cancer (BC) axillary lymph node metastasis detection in a consecutive series of 76 BC patients, 28 of whom had axillary lymph node metastases, including 9 positive at clinical examination. HR planar scintigraphy was true positive in only 7 patients with >3 palpable metastases (sensitivity: 25%), while SPECT was true positive in 23 of 28 cases (sensitivity: 82.1%) and P-SPECT in 25 of 28 (sensitivity: 89.3%). SPECT was false negative in 5 patients with nonpalpable 3 metastatic nodes. SPECT should be preferred, significantly improving the sensitivity of planar scintigraphy, especially when using a pinhole collimator.

The usefulness of 99mTc-tetrofosmin SPECT scintimammography in the detection of small size primary breast carcinomas.

The aim of this study was to evaluate the usefulness of supine 99mTc-tetrofosmin SPECT in the detection of small size breast carcinomas (BC), for which planar scintimammography has showed a low sensitivity. We studied 93 patients with breast lesions

Breast scintigraphy with breast-specific γ-camera in the detection of ductal carcinoma in situ: a correlation with mammography and histologic subtype.

UNLABELLED: Ductal carcinoma in situ (DCIS) is a subtype of breast cancer encountered increasingly in clinical practice because of the widespread use of screening mammography. In the present study, we evaluated the usefulness of breast-specific γ-camera (BSGC) scintigraphy in DCIS identification, describing the scintigraphic findings and their correlation with mammography and histologic subtype. METHODS: Thirty-three women, aged 41-81 y, with surgically proven DCIS were retrospectively reviewed. Before surgery, all patients underwent breast scintigraphy using a high-resolution semiconductor-based BSGC, starting 10 min after intravenous injection of 740 MBq of (99m)Tc-tetrofosmin. All patients had previously undergone mammography. A definitive histologic diagnosis was obtained in all cases after scintigraphy, and the scintigraphic findings were correlated with mammography and histologic subtype. RESULTS: Mammography was positive in 30 of 33 patients (sensitivity, 90.9%), showing calcifications in 22 of 30 (73.3%), masses in 3 of 30 (10%), and masses plus calcifications in the remaining 5 of 30 (16.7%). Scintigraphy was positive in 31 of 33 patients (sensitivity, 93.9%), showing patchy irregular uptake in patients with calcifications and focal uptake in masses; sensitivity was higher in low- to intermediate-grade DCIS than in intermediate/high- and high-grade DCIS (100% vs. 91.3%), but the difference was not statistically significant. Two comedo-type DCIS (one 20-mm intermediate/high-grade and one 15-mm high-grade) with heterogeneously or highly dense breasts at mammography and one papillary low/intermediate-grade DCIS associated with Paget disease were true positive only at scintigraphy. Moreover, scintigraphy better assessed disease extent than did mammography in 5 additional patients. Two comedo-type DCIS (one 6-mm intermediate/high-grade and one 15-mm high-grade) were true positive only at mammography. The difference in sensitivity between scintigraphy and mammography was not statistically significant. The combined use of mammography and scintigraphy achieved 100% sensitivity. CONCLUSION: BSGC scintigraphy proved to be a highly sensitive diagnostic tool in the detection of DCIS, irrespective of histologic subtype, and with a scintigraphic pattern of uptake that correlated well with mammography findings. In our series, BSGC scintigraphy demonstrated a slightly higher sensitivity than mammography and a better assessment of local disease extent. Thus, BSGC scintigraphy should represent a useful adjunctive tool in breast cancer diagnosis.

The clinical impact of breast scintigraphy acquired with a breast specific γ-camera (BSGC) in the diagnosis of breast cancer: incremental value versus mammography.

We investigated the clinical impact of breast scintigraphy acquired with a breast specific γ-camera (BSGC) in the diagnosis of breast cancer (BC) and assessed its incremental value over mammography (Mx). A consecutive series of 467 patients underwent BSGC scintigraphy for different indications: suspicious lesions on physical examination and/or on US/MRI negative at Mx (BI-RADS 1 or 3), characterization of lesions suspicious at Mx (BI-RADS 4), preoperative staging in lesions highly suggestive of malignancy at Mx (BI-RADS 5). Definitive histopathological findings were obtained in all cases after scintigraphy: 420/467 patients had BC, while 47/467 patients had benign lesions. The scintigraphic data were correlated to Mx BI-RADS category findings and to histology. The incremental value of scintigraphy over Mx was calculated. Scintigraphy was true-positive in 97.1% BC patients, detecting 96.2% of overall tumor foci, including 91.5% of carcinomas ≤10 mm, and it was true-negative in 85.1% of patients with benign lesions. Scintigraphy gave an additional value over Mx in 141/467 cases (30.2%). In particular, scintigraphy ascertained BC missed at Mx in 31 patients with BI-RADS 1 or 3, including 26 patients with heterogeneously/high dense breast (19/26 with tumors ≤10 mm) and detected additional clinically occult ipsilateral or controlateral tumor foci (all <10 mm) or the in situ component sited around invasive tumors in 77 BC patients with BI-RADS 4 or 5, changing surgical management in 18.2% of these cases; moreover, scintigraphy ruled out malignancy in 33 patients with BI-RADS 4. BSGC scintigraphy proved a highly sensitive diagnostic tool, even in small size carcinoma detection, while maintaining a high specificity. The procedure increased both the sensitivity of Mx, especially in dense breast and in multifocal/multicentric disease, and the specificity as well as it better defined local tumor extension, thus guiding the surgeon to a more appropriate surgical treatment.

Sentinel node biopsy in early breast cancer: lessons learned from more than 1000 cases at a single institution.

AIMS: The aims of this paper are to report the development of sentinel node biopsy (SNB) in breast cancer at a single institution and to discuss the relevant issues on SNB still to be elucidated. PATIENTS AND METHODS: From 1998 to 2010, 1021 SNBs with frozen section examination were carried out in patients with breast cancer. In the early period (1998-2002) SNB was always combined with axillary lymph node dissection (ALND). From 2002 onwards, only patients with a positive SNB result underwent ALND (late period). The characteristics of patients with infiltrating carcinoma (IC) and ductal carcinoma in situ (DCIS) and the histological status of the sentinel nodes were examined. The survival outcomes of node-negative patients were compared between patients submitted to SNB and ALND (ALND group) during the early period and patients who underwent only SNB during the late period (SNB group). RESULTS: The sentinel node was identified intraoperatively in 98.3% of cases. During the early period the overall accuracy of SNB was 97.0%. During the late period, 700 patients with IC and 140 with DCIS underwent SNB. In the IC group, 149 patients (21.3%) had sentinel node macrometastases and 36 (5.1%) micrometastases; of that subgroup, 21 underwent ALND and no other metastatic lymph nodes were found, and 15 underwent SNB only. Axillary recurrences were observed in 4 patients (0.77%) with negative SNB; none of these were among the patients with micrometastatic SNB. Two patients (1.4%) with DCIS had a positive SNB. In node-negative patients the 5-year overall survival was 96.7% in the ALND group and 96.5% in the SNB group (P = 0.63). The 5-year disease-free survival was 93.8% and 93.2% in the ALND and SNB groups, respectively (P = 0.77). CONCLUSIONS: Overall and disease-free survival in patients with a negative SNB result and no further axillary surgery were equal to those in patients with negative ALND. Intraoperative assessment of the sentinel node in expert hands has a low false-negative rate and allows immediate ALND in patients with sentinel node metastases, avoiding the need for a second operation. ALND for sentinel node micrometastases may be safely omitted in most patients with early stage breast cancer.

The role of planar scintimammography with high-resolution dedicated breast camera in the diagnosis of primary breast cancer.

Planar scintimammography (SM) acquired with a conventional gamma camera has proved a useful complementary tool to mammography (Mx) in breast cancer (BC) diagnosis, but with unsatisfactory sensitivity in small size carcinomas. In this study we assessed the role of planar SM with a high-resolution dedicated breast camera (DBC) in BC diagnosis, comparing the results with those of Mx.A consecutive series of 145 patients scheduled for biopsy for suspected BC underwent Tc-99m tetrofosmin planar SM using a newly developed DBC. Scintigraphic data were compared with Mx findings and correlated to histology.Histopathologic analysis revealed 165 lesions: 143 malignant and 22 benign. SM detected 139/143 carcinomas (overall sensitivity: 97.2%) and was true negative in 19/22 benign lesions (overall specificity: 86.4%). SM sensitivity was 91% in < or =10-mm carcinomas. SM was more accurate than Mx in 42/145 cases (29%), detecting cancer in 9 patients with Mx indeterminate for dense breasts (8/9 tumors were <10 mm), assessing additional tumor foci (all <10 mm) in 5 points with multifocal disease and correctly classifying 28 patients with inconclusive mammographic findings as affected by cancer or by benign disease. Mx was more accurate than SM in 3 patients, in each detecting 1 subcentimeter BC false negative on SM.DBC planar SM seems a highly sensitive diagnostic tool in the detection of BC, even when small in size, and in the assessment of multifocal disease. A wider employment of this procedure is thus suggested, especially in indeterminate or inconclusive mammographic findings to improve sensitivity and specificity of Mx.