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The purpose of this study was to assess the relationship of mammographic breast density (BD) and cell proliferation/focal adhesion kinase activation–seeking radiotracer technetium 99m pentavalent dimercaptosuccinic acid ( 99m Tc(V)-DMSA) uptake in women with different breast histologies, that is, mild epithelial hyperplasia (MEH), florid epithelial hyperplasia (FEH), mixed ductal carcinoma in situ with invasive ductal carcinoma (DCIS + IDC), and pure IDC. Fifty-five women with histologically confirmed mammary pathologies were submitted preoperatively to mammography and 99m Tc(V)-DMSA scintimammography. The percentage and intensity of 99m Tc(V)-DMSA uptake and the percentage of BD were calculated by computer-assisted methods and compared (t-test) between the breast pathologies. In breasts with increased BD, FEH and DCIS + IDC were found. On the contrary, pure IDC and MEH were identified in breasts with significantly lower BD values. In breasts with increased 99m Tc(V)-DMSA area and intensity of uptake, FEH was the main lesion found compared to all other histologies. Linear regression analysis between BD and 99m Tc(V)-DMSA uptake area and intensity revealed significant coefficients of correlation (r 5 .689, p , .001 and r 5 .582, p , .001, respectively). Increased BD correlates with the presence of FEH and mixed DCIS + IDC but not with pure IDC or MEH. Its close relationship to 99m Tc(V)-DMSA, which also showed an affinity to FEH, indicates that stromal microenvironment may constitute a specific substrate leading to progression to different subtypes of cancerous lesions originating from different pathways.

78 Background: The aim of this study was to assess the variation of the serum neo-angiogenic neuropeptide CGRP in patients with benign and malignant breast lesions and to evaluate its possible correlation with mammographic findings. Methods: Our study included forty eight women with histologically confirmed breast lesions: mild epithelial hyperplasia (MEH): n=12, florid epithelial hyperplasia (FEH): n=5, atypical hyperplasia (AH): n=4, ductal carcinoma in situ (DCIS): n=5, mixed in situ with invasive ductal carcinoma (DCIS+IDC): n=9 and pure IDC: n=13. Serum CGRP levels were measured by RIA methods and compared among the various groups by Mann-Whitney test. Mammographic breasy density (BD%) was calculated using computer-assisted methods and was correlated with serum CGRP concentration by applying linear regression analysis. Results: Serum CGRP concentration (mean±SD: pg/mL) in the various groups, was: MEH: 96.8±22.5, FEH: 135.5±33.5, AH: 139±44.4, DCIS: 131.4±37.5, DCIS+IDC: 1167.5±927.5, pure IDC: 198±82. DCIS+IDC lesions presented statistically significantly higher serum CGRP levels (versus: MEH p Conclusions: Statistically increased serum CGRP concentration was determined in women with DCIS+IDC lesions. The significant correlation between serum CGRP levels and BD, enhances the suggestion that DCIS+IDC represents a distinct pathological entity, associated with an interactive mechanism between BD and serum CGRP expression. Therefore, serum CGRP levels could constitute a future useful preoperative index of the nature or type of suspicious mammographic lesions, in order to schedule the appropriate therapeutic treatment, and potentially propounds the perspective of adjunctive therapeutic administration of anti-CGRP peptides.

Aim: To assess neoangiogenesis in relation to breast density (BD), calcitonin gene related peptide (CGRP), cell proliferation seeking radiotracer 99mTc-(V)DMSA uptake (SMM) in invasive ductal associated with extensive in situ carcinoma (DCIS + IDC) and in pure invasive breast carcinoma (IDC). Methods: 20 patients with histologically confirmed mixed DCIS + IDC (n=10) and pure IDC (n=10) were submitted preoperatively to mammography and scintimammography. The percentage of breast density (BD) and the percentage of tracer uptake (SMM) were calculated with computer assisted methods. CGRP and the number of newly formed blood vessels (NBV) were immunohistochemicaly assessed. NBV, BD, CGRP, and SMM were compared (t-test) between the two groups. Linear regression analysis was performed between NBV, BD, CGRP and SMM in both groups. Results: NBV, BD, CGRP and SMM were significantly higher in mixed DCIS + IDC as compared to pure IDC (32.1±10.4 vs 24.3±5 p=0.048, 35.2 ± 6.9 vs 25.6±10.7 p=0.028, 25.5±7.6 vs 17±7.8 p=0.024, 26.75±4.09 vs 11.34±8.5 p=0.0009). NBV was strongly correlated with BD and CGRP in the DCIS component of the mixed group (r=0.933 p Conclusion: Mixed DCIS + IDC lesions exhibit significantly increased NBV, BD, CGRP and SMM values as compared to those of IDC lesions. The strong correlation between neoangiogenesis and the other parameters in the mixed group indicates that the mixed DCIS + IDC constitutes a strictly different entity from pure IDC, more aggressive and probably originates from the stroma through the CGRP pathway. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2381.