Molecular Breast Imaging in Patients with Suspicious Calcifications

Objective We evaluated the accuracy of molecular breast imaging (MBI)—a nuclear medicine technique that employs dedicated dual-detector, cadmium zinc telluride gamma cameras to image the functional uptake of a radiopharmaceutical (typically Tc-99m sestamibi) in the breast—in patients with suspicious calcifications on mammography. Methods Women scheduled for stereotactic biopsy of calcifications detected on 2D digital mammography were prospectively enrolled to undergo MBI before biopsy. Molecular breast imaging was performed with injection of Tc-99m sestamibi and a dual-detector, cadmium zinc telluride gamma camera. Positive findings on either modality were biopsied. High-risk and malignant biopsy findings were excised. Results In 71 participants, 76 areas of calcifications were recommended for biopsy after mammography, and 24 (32%) were malignant, including 20 cases of ductal carcinoma in situ (DCIS) and 4 cases of invasive ductal cancer. Prebiopsy MBI was positive in 17 of the 76 (22%) calcifications, including 10 of 20 (50%) DCISs and 2 of 4 (50%) invasive cancers. The median pathologic size for MBI–positive cancers was 1.5 cm (range 0.5–3.2 cm) compared with 0.9 cm (range 0.1–2.0 cm) for MBI–negative cancers (P = 0.09). Non-mass uptake on MBI led to additional biopsies of 6 sites in 6 patients, and 2 of 6 (33%) MBI–detected incidental lesions showed malignancy; both DCIS contralateral to the mammographically detected calcifications. The overall per-lesion positive and negative predictive values of MBI in this prebiopsy setting were 61% (14 of 23) and 80% (47 of 59), respectively. Conclusion Molecular breast imaging has insufficient negative predictive value to identify calcifications in which biopsy could be avoided. However, among women presenting for biopsy of suspicious calcifications, MBI revealed additional sites of mammographically occult breast cancer. To avoid biopsy of suspicious calcifications on mammography, negative findings on MBI should not be used.

CYTOKINE-PRODUCING RESOURCE OF IMMUNOCOMPETENT BLOOD CELLS IN BREAST TUMORS AND PRECANCEROUS CHANGES OF MAMMARY GLAND

At present, only ductal carcinoma in situ is included into the group of precancerous lesions of mammary ducts, according to International Agency for the Study of Cancer. However, based on recent publications, in addition to ductal carcinoma in situ, sclerosing adenosis, intraductal proliferative lesions and radial scar may be also attributed to precancerous changes. A variety of both benign and malignant events in mammary gland, the features of neoplastic growth and age of the patients require new approaches to study of carcinogenic events in mammary gland. As based on the known role of cytokines in genesis of malignancies, the aim of the study was to evaluate the cytokine-producing resource of immunocompetent blood cells in malignant, benign and precancerous mammary disorders. To assess the cytokine-producing resource of immunocompetent blood cells in the patients, we studied quantitative effects of polyclonal activators upon production of cytokines by immunocompetent blood cells of patients with invasive ductal cancer representing a histological type of adenocarcinoma (group I), and patients with non-malignant breast neoplasias (group II). At subsequent step, the patients with non-malignant neoplasms of the breast were divided into a subgroup of patients with only fibroadenoma and mastopathy (group III), and a group which included patients with precancerous diseases, i.e., sclerosing adenosis and interductal proliferates (group IV). Concentrations of IL-2, IL-6, IL-8, IL-10, IL-17, IL-18, IL-1β, IL-1ra, TNFα, IFNγ, G-CSF, GM-CSF, VEGF, and MCP-1 were determined by solid-phase enzyme immunoassay. When comparing groups I and II, we revealed higher influence of polyclonal activators upon production of G-CSF and GM-CSF in patients with invasive ductal cancer. When comparing the influence of polyclonal activation for cytokine production in patients of I and III groups, higher values were registered in patients with invasive ductal cancer (production of IL-2, G-CSF, and GM-CSF), and in patients with fibroadenoma and mastopathy (IL-18, and TNFαproduction). When comparing patients of groups I and IV, higher indexes of the polyclonal activator effects were found only for IL-1ra, G-CSF, and VEGF production in invasive ductal cancer. When comparing the indexes of polyclonal activator influence upon cytokine production of groups III and IV, higher values were obtained in patients with benign changes for the following cytokines: IL-8, IL-18, IL-1β, IL-1ra and TNFα, in contrast to patients with sclerosing adenosis and proliferates. The lower indexes of polyclonal activating effects upon the production of a number of cytokines in patients with precancerous changes, as compared to patients with malignant and benign breast tumors, do not indicate a decreased functional activity of immunocompetent blood cells. However, those may be due to high level of spontaneous cytokine production in sclerosing adenosis and interductal proliferates.

Breast Cancer Case Using Tamoxifen during Pregnancy: A Case Report and Literature Review

<p>This is a case of 32 years old nulliparous female who was diagnosed in November 2004 as a case of carcinoma of the right breast , luminal A , (Estrogen Receptor positive Progesterone receptor negative, Her 2 negative, Ki67 10 %), poorly differentiated invasive ductal cancer, TNM stage,T2 N0 MO. She had a wide local excision and axillary clearance. As she is a case of low risk early stage luminal A breast cancer; she was not given chemotherapy, instead she had a course of external irradiation and was put on Tamoxifen (Astra Zeneca, 20 mg daily), and was advised not to get pregnant during this treatment,but she got pregnant and delivered normally a healthy infant, although Tamoxifen is potentially teratogenic.</p>

Histogram analysis of volume-based apparent diffusion coefficient in breast cancer

Background Breast cancer is a heterogeneous disease. Recent studies showed that apparent diffusion coefficient (ADC) values have various association with tumor aggressiveness and prognosis. Purpose To evaluate the value of histogram analysis of ADC values obtained from the whole tumor volume in invasive ductal cancer (IDC) and ductal carcinoma in situ (DCIS). Material and Methods This retrospective study included 201 patients with confirmed DCIS (n = 37) and IDC (n = 164). The IDC group was divided into two groups based on the presence of a DCIS component: IDC–DCIS (n = 76) and pure IDC (n = 88). All patients underwent preoperative breast magnetic resonance imaging (MRI) with diffusion-weighted images at 3.0 T. Histogram parameters of cumulative ADC values, skewness, and kurtosis were calculated and statistically analyzed. Results The differences between DCIS, IDC–DCIS, and pure IDC were significant in all percentiles of ADC values, in descending order of DCIS, IDC–DCIS, and pure IDC. IDC showed significantly lower ADC values than DCIS, and ADC50 was the best indicator for discriminating IDC from DCIS, with a threshold of 1.185 × 10–3 mm2/s (sensitivity of 82.9%, specificity of 75.7%). However, multivariate analysis of obtained ADC values showed no significant differences between DCIS, IDC–DCIS, and pure IDC ( P > 0.05). Conclusion Volume-based ADC values showed association with heterogeneity of breast cancer. However, there was no additional diagnostic performance in histogram analysis for differentiating between DCIS, IDC–DCIS, and pure IDC.

Cytokine profiles of tumor supernatants in invasive ductal cancer and fibroadenoma of the breast and its relationship with VEGF-A expression in the tumors

Interrelations between cytokines, produced by invasive ductal carcinoma (IDC) and fibroadenoma (FA) of the breast, and angiogenic growth factor VEGF-A, expressed in IDC and FA, were investigated. The analysis of the cytokine profiles of IDC and FA was performed by cultivation of tumor biopsy specimens in vitro. Testing of the cytokine-producing reserve of the tumors for production of VEGF-A was conducted by culturing samples of IDC and FA in a medium containing polyclonal activator (a complex of phytohemagglutinin, concanavalin A, and lipopolysaccharide). Levels of cytokines and growth factors (IL-2, IL-6, IL-8, IL-10, IL-17, IL-18, IL-1β, IL-1Ra, TNF-α, IFN-γ, G-CSF, GM-CSF, VEGF-A) and MCP-1 (monocyte chemoattractant protein-1) in tumor supernatants were determined by an ELISA. Expression of VEGF-A was analyzed in tumor biopsy specimens by immunohistochemical analysis. In the IDC supernatants, the concentrations of IL-17, IL-18, and IFN-γ were higher and the concentrations of IL-10 and MCP-1 were lower in comparison with the FA supernatants. We observed negative correlations between the macrophage infiltration and VEGF-A concentration in the IDC supernatants (r = −0.508; P = 0.011) and between VEGF-A expression and the IDC vascularization degree (r = −0.423, P = 0.039). Spontaneous expression of VEGF-A in samples of IDC significantly exceeded the VEGF-A expression in FA. There was no difference between IDC and FA in VEGF-A expression after treatment with the polyclonal activators. Our results indicate that greater malignancy may have a paradoxical effect that is controlled by cytokines and characterized by weakening of tumor angiogenesis during overproduction of VEGF-A. These findings point to complex mechanisms of positive and negative regulation of tumor angiogenesis by cytokines that are produced by the tumor and by cells in its microenvironment, whose cytokine profiles may change at different stages of tumor progression.