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Hematopoietic stem cell transplantation (HSCT) recipients have been reported to have an increased risk of chronic graft versus host disease (cGVHD) and hematological and solid cancers. Oral manifestations are the first signs of cGVHD observed in the majority of patients, and oropharyngeal cancer is the most frequent secondary malignancy occurred after HSCT. In this study, we have evaluated the inflammatory infiltrate cell content and correlated with the vascular density in patients affected by primary oral squamous cell carcinoma (OSCC) from previous healthy controls and OSCC after cGVHD. Results have demonstrated that patients with OSCC after GVHD show a more consistent inflammatory infiltrate as compared with the OSCC ones. In detail, the inflammatory background composed of CD3-positive T cells, tryptase-positive mast cells, CD31-positive endothelial cells, and CD68-positive macrophages may be more pronounced in the setting of GVHD + OSCC than in the control group. By contrast, CD20-positive B cells and CD1a-positive dendritic cells were more abundant in the latter population. Finally, a positive correlation was found as between vascular density and inflammatory cell infiltration in both GVHD + OSCC and OSCC groups. Overall, these results confirm the role played by immune cells in enhancing tumor progression and angiogenesis and suggest a potential therapeutic strategy involving inhibition of recruitment of immune cells to the tumor microenvironment and blockade of pro-tumoral effects and pro-angiogenic functions. [ABSTRACT FROM AUTHOR]

Introduction The 2013 St-Gallen International Expert Panel recognized substantial progress in the pathological characterization of breast cancer subtypes. Useful surrogate definition of Luminal A-like as distinct from Luminal B-like disease could be made using a combination of estrogen receptor (ER), progesterone receptor (PgR) and Ki-67, without requiring molecular diagnostics. Differences depend upon the choice of the threshold value for Ki-67 and the requirement for substantial PgR positivity. We aimed to verify the suitability of the new surrogate definition of luminal subtypes in terms of distant disease control in a large series of patients. Methods 9,415 women with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative, early breast cancer, operated at the European Institute of Oncology during 1994-2006, were followed for a median of 8.1 years. We evaluated distant disease-free survival of patients with "low" (<14%), "intermediate" (14-19%), and "high" (⩾20%) Ki-67 stratified by PgR expression ("negative or low" versus ⩾20%). We calculated the cumulative incidence of distant events considering competing events and performed multivariable analysis adjusted for pT, pN, grade, peritumoral vascular invasion (PVI) and menopausal status. Results Lack of substantial PgR positivity was associated with poorer outcome only for patients with "intermediate" Ki-67 (P < 0.001). The 4,890 (51.9%) patients with "low" Ki-67 (any PgR) or with "intermediate" Ki-67 but substantial PgR positivity had a comparable good outcome and may represent a most advantageous grouping of those with 'Luminal A-like' disease. Conclusions This updated pathological definition of intrinsic molecular subtypes may maximize the number of patients classified as having 'Luminal A-like' intrinsic subtype for whom use of cytotoxic drugs could be at large avoided. [ABSTRACT FROM AUTHOR]

Several small studies have reported that having a high percentage of breast tumor cells that express the proliferation antigen Ki-67 (ie, a high Ki-67 labeling index) predicts better response to neoadjuvant chemotherapy. However, the predictive value of a high Ki-67 labeling index for response to adjuvant chemotherapy is unclear. To investigate whether Ki-67 labeling index predicts response to adjuvant chemoendocrine therapy, we assessed Ki-67 expression in tumor tissue from 1924 (70%) of 2732 patients who were enrolled in two randomized International Breast Cancer Study Group trials of adjuvant chemoendocrine therapy vs endocrine therapy alone for node-negative breast cancer. A high Ki-67 labeling index was associated with other factors that predict poor prognosis. Among the 1521 patients with endocrine-responsive tumors, a high Ki-67 labeling index was associated with worse disease-free survival but the Ki-67 labeling index did not predict the relative efficacy of chemoendocrine therapy compared with endocrine therapy alone. Thus, Ki-67 labeling index was an independent prognostic factor but was not predictive of better response to adjuvant chemotherapy in these studies. [ABSTRACT FROM AUTHOR]

Aim Breast International Group (BIG) 2–98 is a randomised phase III trial that tested the effect of adding docetaxel, either in sequence to or in combination with anthracycline-based adjuvant chemotherapy, in women with node-positive breast cancer (BC). Here, we present the 10-year final trial safety and efficacy analyses. We also report an exploratory analysis on the predictive value of Ki67 for docetaxel efficacy, in the BIG 2–98 and using a pooled analysis of three other randomised trials. Patients and methods 2887 patients were randomly assigned in a 2 × 2 trial design to one of four treatments. The primary objective was to evaluate the overall efficacy of docetaxel on disease free survival (DFS). Secondary objectives included comparisons of sequential docetaxel versus sequential control arm, safety and overall survival (OS). Ki67 expression was centrally evaluated by immunohistochemistry. Results After a median follow-up of 10.1 years, the addition of docetaxel did not significantly improve DFS or OS (hazard ratio (HR) = 0.91, 95% confidence interval (CI) = 0.81–1.04; P = 0.16 and HR = 0.88, 95% CI = 0.76–1.03; P = 0.11, respectively). Sequential docetaxel did not improve DFS compared to the sequential control arm (HR = 0.86, 95% CI = 0.72–1.03; P = 0.10). In oestrogen receptor (ER)-positive tumours with Ki67 ⩾ 14%, the addition of docetaxel resulted in 5.4% improvement in 10-year OS ( P = 0.03, test for interaction = 0.1). In a multivariate model, there was a trend for improved DFS and OS in ER-positive patients with high Ki67 and treated with docetaxel (HR = 0.79, 95% CI = 0.63–1.01; P = 0.05 and HR = 0.76, 95% CI = 0.57–1.01; P = 0.06, respectively). A pooled analysis of four randomised trials showed a benefit of taxanes in highly proliferative ER-positive disease but not in low proliferating tumours (interaction test P = 0.01). Conclusion The DFS benefit previously demonstrated with sequential docetaxel is no longer observed at 10 years. However, an exploratory analysis suggested a benefit of docetaxel in patients with highly proliferative ER-positive BC. [ABSTRACT FROM AUTHOR]