Dual-Energy CT for Locoregional Staging of Breast Cancer: Preliminary Results.

OBJECTIVE. The objective of this study was to demonstrate the feasibility of dual-energy CT (DECT) for locoregional staging of breast cancer and differentiation of tumor histotypes. MATERIALS AND METHODS. From January 2016 to July 2017, a total of 31 patients (mean [± SD] age, 55.8 ± 14.8 years) with breast cancer diagnosed by needle biopsy who underwent preoperative contrast-enhanced DECT for staging purposes were selected from a retrospective review of institutional databases. Monochromatic images obtained at 40 and 70 keV were evaluated by two readers who determining the number of hypervascularized tumors present and the largest tumor diameter for each breast. The attenuation values and iodine concentration of tumors and normal breast tissue and the ratios of these findings in each tissue type were recorded. Cancers were classified as ductal carcinoma in situ, invasive ductal carcinoma, and invasive lobular carcinoma. The reference standard was the final pathologic finding after surgery. RESULTS. A total of 64 tumor lesions were found at histopathologic analysis versus 67 on DECT for 34 breasts (three bilateral cancers were included). Nonparametric statistics were used. The largest lesion diameter observed DECT was 33.2 ± 20.5 mm versus 31.8 ± 20.5 mm on pathologic analysis, and cancer distribution was correctly classified for 31 of 34 (91%) cases. ROC curves derived from lesion iodine concentration showed that the optimal thresholds for distinguishing infiltrating carcinomas (invasive lobular and ductal carcinomas) and from other lesions were 1.70 mg/mL (sensitivity, 94.9%; specificity, 93.0%; AUC value, 0.968). ROC curves derived from the ratio of the iodine concentration in lesions to that in normal breast parenchyma showed that 6.13 was the optimal threshold to distinguish invasive ductal carcinoma from other lesions (sensitivity, 87.0%; specificity, 81.1%; AUC value, 0.914). CONCLUSION. DECT is feasible and seems to be a reliable tool for locoregional staging of breast cancer.

"Clinical significance of multifocal and multicentric breast cancers and choice of surgical treatment: a retrospective study on a series of 1158 cases".

BACKGROUND: The biological and clinical significance of multifocal and multicentric (MF/MC) breast cancers and the choice of appropriate surgical treatment for these tumors are still debated. METHODS: 1158 women operated on for a stage I-III breast cancer were included in this retrospective study; clinical and pathological data were obtained from the institutional database of the Department of Oncology of the University of Siena, Italy. The impact of MF/MC breast cancers on patterns of recurrence and breast cancer specific survival (BCSS) was investigated in relation to the type of surgical treatment. RESULTS: MF and MC cancers were present in 131 cases (11.3%) and 60 cases (5.2%) respectively and were more frequently treated with mastectomy (55 MF and 60 MC cancers, 81.2%) than with breast conserving surgery (36 MF cancers, 18.9%; p < 0.001). MF and MC breast cancers were associated with a worse prognosis with a BCSS of 154 months compared to 204 months of unicentric cancers (p < 0.001). In multivariate analysis, MF/MC cancers were independent prognostic factors for BCSS together with higher number of metastatic axillary nodes, absence of estrogen receptors and high proliferative activity. MF and MC cancers were related to a significantly shorter BCSS in patients submitted to mastectomy as well as those submitted to breast conserving surgery. Relapse at any site was higher in the subgroup of MF and MC cancers but the incidence of loco-regional and distant recurrences did not differ between patients treated with mastectomy or breast conserving surgery. CONCLUSIONS: Our results indicate that MF/MC cancers have a negative impact on prognosis and are related to higher loregional and distant relapse independently from the type of surgery performed. Adjuvant therapies did not modify the poorer outcome, but in patients receiving adjuvant anthacyclines, the differences with unicentric tumors were reduced. Our data support the hypothesis that MF/MC tumors may have a worse biological behavior and that the presence of multiple foci should be considered in planning adjuvant treatments.

Is tissue inhibitor of metalloproteinase-1 a new prognosticator for breast cancer? An analysis of 266 cases.

Overexpression of tissue inhibitor of metalloproteinase-1 at either the messenger RNA or protein level has been related to a poorer prognosis in breast cancer. We investigated the role of tissue inhibitor of metalloproteinase-1 tissue expression, which was evaluated by immunohistochemistry staining of paraffin-embedded samples, as a possible prognostic indicator in breast cancer. The study included 266 patients treated by primary surgery. Tumors were scored tissue inhibitor of metalloproteinase-1 positive when at least 10% of the cells showed moderate or strong staining. Staining was observed in 76 (28.6%) patients; by multivariate analysis, factors independently associated with tissue inhibitor of metalloproteinase-1 positivity included more than 9 metastatic axillary nodes, high Mib-1 expression, and positivity for plasminogen activator inhibitor and CD44. With a median follow-up of 125 months, tissue inhibitor of metalloproteinase-1 expression showed a significant prognostic role in disease-free and overall survival by univariate analysis. Multivariate analysis confirmed an independent negative prognostic impact of tissue inhibitor of metalloproteinase-1 on overall but not disease-free together with high values of Mib-1. The number of involved axillary nodes, and triple negativity were independent predictors of either poorer disease-free or overall survival. In our study, tissue inhibitor of metalloproteinase-1 expression was significantly related to markers of tumor aggressiveness and was a powerful indicator of poorer prognosis, with a difference in 10-year disease-free and overall survival of 14% and 28%, respectively, between tissue inhibitor of metalloproteinase-1-negative and tissue inhibitor of metalloproteinase-1-positive cases. Expression of tissue inhibitor of metalloproteinase-1 also was an independent prognostic factor in node-positive cases, indicating a possible role of tissue inhibitor of metalloproteinase-1 as a marker of reduced chemosensitivity. Thus, tissue inhibitor of metalloproteinase-1 may have a role in clinical practice as a prognostic and predictive factor and a possible target for future therapies.

Traditional and new prognosticators in breast cancer: Nottingham index, Mib-1 and estrogen receptor signaling remain the best predictors of relapse and survival in a series of 289 cases.

Histopathological and immunohistochemical findings on tissue microarrays, overall survival (OS), disease-free survival (DFS) and incidence of relapses (R) were recorded and statistically analyzed in 289 breast cancers. A higher R and a shorter DFS were significantly related to larger tumors, lymph node invasion, higher tumor grade, absence of estrogen receptors (ER), triple negative tumors, and presence of lymphovascular invasion (LVI). Longer OS was observed to be significantly associated with smaller tumor size (T), lymph node negativity, lower tumor grade, absence of LVI, lower Mib-1 expression and with the presence of ER. At multivariate analysis, only T for DFS and lymph node status and triple negativity either for DFS or OS had independent prognostic value. In the 194 lymph node-negative women DFS and OS were inversely related to tumor grade, absence of ER, Mib-1 expression in more than 15% of neoplastic cells and, only for DFS, presence of LVI. In the 95 lymph node-positive the number of involved nodes was the most discriminating parameter either for DFS or OS; T, Her-2 status and presence of LVI were significantly related to DFS. ER negativity was related to higher grade, progesterone receptors (PR) negativity, Her-2 negativity, hence to triple negativity, to basal-like type, Mib-1expression over 15% of neoplastic cells. Her-2 positivity was related to higher grade, ER positivity and PR positivity. Basal-like type was not an independent prognosticator, while triple negative type has a significant relation to shorter OS. The Nottingham prognostic index accurately identifies prognostic groupings and Mib-1 expression and ER signaling are the key biological predictors even in single cases.

Bcl-2 expression correlates with lymphovascular invasion and long-term prognosis in breast cancer.

Alterations in the mechanisms of apoptosis are responsible not only for the progression of breast cancer, but for different responses to treatment as well. Among the genes regulators of apoptosis, the tumor suppressor gene p53 and the bcl-2 gene have raised interest for their possible role as predictors of response to therapy and markers of prognosis. The purpose of our study was to prospectively analyze the prognostic value of the expression of p53 and bcl-2 genes in a series of 235 consecutive patients operated on for breast cancer at the Department of General Surgery and Surgical Oncology of the University of Siena, Italy.p53 and bcl-2 expression were evaluated by immunohistochemistry, their association with conventional clinicopathological factors was analyzed by univariate analysis and their prognostic impact was evaluated by multivariate analysis.p53 and bcl-2 were detected respectively in 15.7 and 75.7% of cases, and resulted significantly related to presence of estrogen receptors for p53 over-expression and presence of peritumor lymphovascular invasion (LVI) for bcl-2 expression. With a median follow-up of 79 months, an independent negative prognostic impact on disease free and overall survival was observed for presence of LVI, absence of bcl-2 expression and number of involved axillary lymphnodes. The expression of bcl-2 improved the prognosis of LVI positive tumors up to values similar to LVI negative cases, while its absence associated to presence of LVI resulted in a poor outcome with only 28% of patients alive at 8 years. These data may indicate that expression of bcl-2 is a marker of breast cancers with reduced capability of distant colonization, even in presence of LVI, and may be particularly useful in the clinical setting, allowing to identify a subset of patients with an high risk of relapse.

Mib-1 proliferation index is an independent predictor of lymph node metastasis in invasive breast cancer: a prospective study on 675 patients.

In order to evaluate the potential risk factors for lymph node metastasis in invasive breast cancer patients submitted to axillary dissection, 675 patients who received surgery between January 1995 and December 2002 were included in a prospective study. In all cases, MIB-1 proliferation index was investigated by immunohistochemistry. Lymph node involvement was found in 248 out of 675 patients. Univariate analysis showed that peritumoral lymphovascular invasion, pT stage, tumor multiplicity, MIB-1 proliferation index >10%, oestrogen receptor status, histological type, tumor grade and progesterone receptor status were related to a higher incidence of lymph node metastasis, with various levels of statistical significance. Multivariate analysis identified lymphovascular invasion [relative risk (RR, 7.69; p<0.001), pT stage (RR, 3.08; p<0.001), tumor multiplicity (RR, 3.89; p<0.001), and MIB-1 proliferation index (RR, 1.66; p=0.019)] as independent predictive variables. The impact of MIB-1 positivity on the incidence of lymph node metastasis was particularly evident in intermediate risk groups (pT1c, pT2 without lymphovascular invasion), as well as in grade-2 tumors. In conclusion, the MIB-1 proliferation index could provide additional information about the risk of lymph node metastasis in invasive breast cancer, and may be useful to identify grade-2 tumors with a more aggressive clinical behaviour.