"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.

Breast conservative surgery for well-differentiated ductal intraepithelial neoplasia: Risk factors for ipsilateral breast tumor recurrence.

RATIONAL: We retrospectively analyzed 232 patients affected by well differentiated ductal intraepithelial neoplasia (DIN1c or DCIS G1) treated with conservative surgery without adjuvant radiotherapy. RESULTS: 25 invasive and 18 non-invasive local recurrences were observed (median follow-up 80 months; 5-year cumulative incidence: 12.2%). Seven of the 15 young patients (<40 y) developed local recurrence (2 in situ, 5 invasive). Age <50 (HR 1.89, 95% C.I. 1.01-3.45), multifocality (HR 3.21, 95% C.I. 1.46-7.06), Ki-67 > 7% (HR 2.33, 95% C.I. 1.20-4.55) and surgical margins <10 mm (HR 2.00, 95% C.I. 1.06-3.76) were significantly associated with an increased risk of local recurrence. CONCLUSIONS: Young age, multifocality and small margins appeared as clear risk factors of local recurrence in DIN1c (DCIS G1) population. The presence of multiple poor prognostic features warrant a thorough discussion regarding local treatment.

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.

Gastric linitis plastica: which role for surgical resection?

BACKGROUND: The role of surgery for gastric linitis plastica (GLP) is questioned. This study aimed to analyze our experience in the surgical treatment of GLP with specific reference to the resectability rate, prognosis, and mode of recurrence. METHODS: Results of surgery were analyzed in 102 patients with GLP. RESULTS: Of the 102 patients, 92 underwent surgical exploration, with resection performed in 60 cases. R2 resection was carried out in 20 patients and R1 in 12 patients, while the resection was considered potentially curative (R0) in 28 (27.5%). Overall, the median (95% confidence interval [CI]) survival time was 5.7 (3.7-7.5) months, with none of the patients alive at the end date of the study. For R0 patients the median (95% CI) survival time was 15.8 (11-20.7) months. The great majority of recurrences were intra-abdominal (peritoneal and/or locoregional), with a systemic component of the relapse that was rarely observed (5 cases). CONCLUSIONS: After primary surgery, GLP showed a poor prognosis without regard to the extent or type of resection. The failure of surgical treatment related mainly to the peritoneal spread of the disease. Specifically designed multimodality treatment protocols should be tested in this setting.

Is circulating D-dimer level a better prognostic indicator than CEA in resectable colorectal cancer? Our experience on 199 cases.

PURPOSE: To evaluate the clinical impact of D-dimer (DD) as a tumor marker in patients with colorectal cancer (CRC). The prognostic value of preoperative DD measurement was assessed in relation to carcinoembryonic antigen (CEA) levels. METHODS: DD and CEA levels were measured preoperatively in 199 patients who underwent resection for CRC and the results were analyzed statistically. RESULTS: The preoperative mean (± SD) levels of DD and CEA were 347.5 (± 940.1) ng/mL and 106.4 (± 1099.2) ng/mL. The DD level was significantly correlated with the nature of surgery (emergency vs. elective; p=0.002), presence of residual tumor (R1-2 vs R0; p=0.037), and tumor diameter (p<0.001). Conversely, DD was not correlated with tumor grade, pT, pN and M stages, and stage according to the Dukes classification. The 5-year survival rates were 80% and 64% for patients with negative and positive DD values, respectively (p=0.156). CEA was significantly related to all major prognostic factors (resection category, pT, pN and M stages as well as Dukes stage). A significantly worse prognosis was observed for patients with positive CEA levels. Multivariate analysis confirmed CEA as an independent prognostic factor (p=0.005), whilst DD was not (p=0.796). CONCLUSIONS: The possible clinical usefulness of preoperative assessment of DD suggested by previous studies has not been confirmed by our data. CEA was confirmed to be the most reliable and valid indicator of prognosis.

Evidence of tumor microsatellite instability in gastric cancer with familial aggregation.

About 90% of gastric cancer (GC) cases appear in a sporadic setting. Nonetheless, in high incidence areas high familial aggregation rates have been recently described. Microsatellite instability (MSI) is thought to be an important molecular phenotype both in sporadic GC and in tumors of the HNPCC spectrum. The aim of this study was to assess the frequency of MSI in GC with familial aggregation. Five quasimonomorphic mononucleotide repeats (BAT-26, BAT-25, NR-24, NR-21 and NR-27) were analyzed in 250 GC patients. Seventy-five patients (30%) had at least one-first-degree family member affected by GC and 63 patients (25.2%) showed MSI. The frequency of MSI was significantly higher in patients with a positive family history of GC (38.7%) compared to patients with other tumor types within the family (15.7%) or with a negative oncological familial history (21.9%, P = 0.004). Within cases with a positive familial oncological history, the MSI frequency in families with GC only was similar to the one observed in families with GC and colon cancer (P = 0.96). Nonetheless, in families with GC and lung cancer, the frequency of MSI was significantly lower (5.6%, P = 0.007). MSI occurs in GCs with familial aggregation. Similar MSI rates have been observed in GC patients with other family members affected by GC or colon cancer. The same does not occur in families with other members affected by lung cancer. Our data seem to suggest that familial aggregation for either GC alone or gastric and colon cancer share common etiological factors in contrast to families with gastric and lung cancers.