Factors that predict early treatment failure for patients with locally advanced (T4) breast cancer

Locally advanced breast cancer (LABC) is associated with dire prognosis despite progress in multimodal treatments. We evaluated several clinical and pathological features of patients with either noninflammatory (NIBC, cT4a-c) or inflammatory (IBC, cT4d) breast cancer to identify subset groups of patients with high risk of early treatment failure. Clinical and pathological features of 248 patients with LABC, who were treated with multimodality treatments including neoadjuvant chemotherapy followed by radical surgery and radiotherapy were reassessed. Tumour samples obtained at surgery were evaluated using standard immunohistochemical methods. Overall, 141 patients (57%) presented with NIBC (cT4a-c, N0-2, M0) and 107 patients (43%) with IBC (cT4d, N0-2, M0). Median follow-up time was 27.5 months (range: 1.6–87.8). No significant difference in terms of recurrence-free survival (RFS) (P=0.72), disease-free survival (DFS) (P=0.98) and overall survival (OS) (P=0.35) was observed between NIBC and IBC. At the multivariate analysis, patients with ER- and PgR-negative diseases had a significantly worse RFS than patients with ER- and/or PgR-positive diseases (hazard ratio: 2.47, 95% CI: 1.33–4.59 for overall). The worst RFS was observed for the subgroup of patients with endocrine nonresponsive and HER2-negative breast cancer (2-year RFS: 57% in NIBC and 57% in IBC) A high Ki-67 labelling index (>20% of the invasive tumour cells) and the presence of peritumoral vascular invasion (PVI) significantly correlated with poorer RFS in overall (HR 2.69, 95% CI: 1.61–4.50 for Ki-67>20% and HR 2.27, 95% CI: 1.42–3.62 for PVI). Patients with endocrine nonresponsive LABC had the most dire treatment outcome. High degree of Ki-67 staining and presence of PVI were also indicators of higher risk of early relapse. These factors should be considered in therapeutic algorithms for LABC

FOXP3+ Tregs and B7-H1+/PD-1+ T lymphocytes co-infiltrate the tumor tissues of high-risk breast cancer patients: Implication for immunotherapy

<p>Abstract</p> <p>Background</p> <p>Recent studies have demonstrated a direct involvement of B7-H1, PD-1 and FOXP3 molecules in the immune escape of cancer. B7-H1 is an inhibitory molecule that binds to PD-1 on T lymphocytes, while FOXP3 is a marker for regulatory T cells (T_regs). We have previously demonstrated the association of B7-H1-expressing T infiltrating lymphocytes (TIL) with high-risk breast cancer patients while other studies reported the involvement of FOXP3+ T_regsas a bad prognostic factor in breast tumors. Although the co-existence between the two types of cells has been demonstrated <it>in vitro </it>and animal models, their relative infiltration and correlation with the clinicopathological parameters of cancer patients have not been well studied. Therefore, we investigated TIL-expressing the B7-H1, PD-1, and FOXP3 molecules, in the microenvironment of human breast tumors and their possible association with the progression of the disease.</p> <p>Methods</p> <p>Using immunohistochemistry, tumor sections from 62 breast cancer patients were co-stained for B7-H1, PD-1 and FOXP3 molecules and their expression was statistically correlated with factors known to be involved in the progression of the disease.</p> <p>Results</p> <p>A co-existence of B7-H1⁺T lymphocytes and FOXP3⁺T_regswas evidenced by the highly significant correlation of these molecules (<it>P </it>< .0001) and their expression by different T lymphocyte subsets was clearly demonstrated. Interestingly, concomitant presence of FOXP3⁺T_regs, B7-H1⁺and PD-1⁺TIL synergistically correlated with high histological grade (III) (<it>P </it>< .001), estrogen receptor negative status (<it>P </it>= .017), and the presence of severe lymphocytic infiltration (<it>P </it>= .022).</p> <p>Conclusion</p> <p>Accumulation of TIL-expressing such inhibitory molecules may deteriorate the immunity of high-risk breast cancer patients and this should encourage vigorous combinatorial immunotherapeutic approaches targeting T_regsand B7-H1/PD-1 molecules.</p

Clinical peri-implant outcomes, technical complications, and patient satisfaction with single vs. splinted crown supported implants in the anterior mandible region of diabetic individuals

OBJECTIVE: To compare the clinical and radiographic peri-implant parameters around narrow diameter implants (NDI) supported single (NDISCs) and splinted crowns (NDISPs) in the anterior maxilla of non-diabetics and type 2 diabetes mellitus patients (T2DM). MATERIALS AND METHODS: The clinical and radiographic parameters of NDISC and NDISP were assessed in the anterior mandibular jaw of T2DM and non-diabetic individuals. Plaque index (PI), bleeding on probing (BoP), probing depth (PD) and crestal bone levels were recorded. Technical complications and patient satisfaction were also assessed. ANOVA (one-way analysis of variance) was used to compare the inter-group means of clinical indices and radiographic bone loss while Shapiro-Wilk was used to compute the normal distribution of dependent variables. A p-value of less than 0.05 was considered significant. RESULTS: Sixty-three patients (35 males and 28 females) were part of the study out of which 32 were non-diabetics and 31 were T2DM patients. A total of 188 implants (124 NDISCs and 64 NDISPs) having moderately roughened topography were used for the study. The mean glycated hemoglobin in the non-diabetic group was 4.3 while that in the T2DM group was 7.9 with an average diabetic history of 8.6 years. Peri-implant parameters, including PI, BoP, and PD, were comparable between the single crown and splinted crown groups. However, there was a statistically significant difference in PI, BoP, and PD when a comparison was made between the non-diabetes and T2DM groups (p<0.05). An overall 88% of the patients were satisfied with the esthetics of the crowns while 75% of the subjects were satisfied with the function of the crowns. CONCLUSIONS: Narrow diameter implants of both types had satisfactory clinical and radiographic outcomes within non-diabetic and diabetic individuals. However, clinical and radiographic parameters were worse in type 2 diabetes mellitus patients when compared to non-diabetics

Sociodemographic characteristics and sexual behavior as risk factors for human papillomavirus infection in Saudi Arabia

This article seeks to determine the prevalence and the sociodemographic characteristics and sexual behavior risk factors for human papillomavirus (HPV) infection in a hospital-based cohort of women in Saudi Arabia