Metastatic breast cancer subtypes and central nervous system metastases

e11581 Background: The relapse pattern, survival and response to therapy are known to be different between breast cancer (BC) subtypes defined by combining hormone-receptor (HR) and HER2 status. Our aim was to study incidence and predictors of central nervous system metastases (CNS-M) and the outcome after CNS-M according to tumor subtype. Methods: 488 patients (pts) treated with at least one line of chemotherapy for metastatic BC were retrospectively evaluated. According to the combination of HR and HER2 status, tumors were grouped in: Luminal (Lum): HR+/HER2-, Luminal/HER2+ (Lum/HER2+): HR+/HER2+, pure HER2 positive (pHER2+): HR-/HER2+, and triple negative (TN): HR-/HER2-. All HER2+ patients received treatment with Lapatinib or Trastuzumab in addition to chemotherapy for metastatic disease. Median follow up was 34 months. Results: 133 pts (27%) developed CNS-M, with a median time to CNS progression of 43 months. The rate of CNS-M by subtype was: Lum 18%, Lum/HER2+ 37%, pHER2+ 49%, TN 25% (p <0.001). Multivariate analysis confirmed that, compared with Lum tumors, Lum/HER2+ ( HR 2.556, p<0.001), pHER2+ (HR 4.444, p<0.001) and TN (2.249, p=0.011) subtypes were at higher risk of CNS-M. Median overall survival (OS) CNS-M was 8.8 months in the whole series (IC 95% 6.6-11.0). Median OS in months by subtype was: Lum 9, Lum/HER2+ 18, pHER2+ 7, TN 7 (p<0.001). Multivariate analysis revealed that belonging to the Lum/HER2+ subtype (HR 0.528 compared with the Lum subtype, p<0.001) and having isolated CNS (HR 0.398, compared with CNS-M plus systemic progression, p<0.001) predicted significantly reduced risk of death. Conclusions: Among pts with a known increased risk of brain metastases, the Lum/HER2+ subtype appears associated with the longest OS after CNS-M, probably due to different biology and better extracranial disease control by chemotherapy, hormonal therapy and target agents. These results suggest that these patients may benefit from a more aggressive treatment of CNS-M and, possibly, from the screening for asymptomatic CNS lesions

Agronomic and molecular analyses for the characterisation of accessions in Tunisian olive germplasm collections

In this study, a total of 14 agronomic traits, five AFLP primer combinations and ten SSR loci were used to describe and to classify a group of Tunisian olive genotypes into groups based on molecular profiles and agronomic traits. The analysis of variance of the agronomical data revealed significant differences among accessions for all measured traits. The mean phenotypic dissimilarity (0.34 with a range of 0.08-0.6) was low in comparison to dissimilarity calculated using AFLP (0.50 with a range of 0.16-0.70) and SSR markers (0.76 with a range 0.35-0.94). The correlation between the agronomical dissimilarity matrix and the matrices of genetic dissimilarity based on SSR and AFLP markers was very weak: 0.156 (p = 0.05) and 0.185 (p = 0.05), respectively. The SSR-AFLP dendrogram based on unweighted pair-group cluster analysis using Jaccard\u2019s index revealed that the genetic diversity was predominantly structured according to fruit size. A trend of clustering together of accessions originating from the same or adjacent regions was also observed. The data obtained can be used for the varietal survey and construction of a database of all olive varieties grown in Tunisia and providing also additional information that could form the basis for the rational design of breeding programs

Insertion/Deletion markers for assessing the genetic variation and the spatial genetic structure of Tunisian Brachypodium hybridum populations

The wild annual grass Brachypodium hybridum, an allotetraploid species derived from the natural hybridization between the diploid species B. distachyon (2n=10) and B. stacei (2n=20). This trio of species has been suggested as a model system for polyploidy. Brachypodium hybridum is the most widespread Brachypodium species in Tunisia. Natural diversity can be used as a powerful tool to uncover gene function and, in the case of B. hybridum, to understand the functional consequences of polyploidy. Here, we examined the spatial distribution of genetic variation of B. hybridum across its entire range in Tunisia and tested underlying factors that shaped its genetic variation. Population genetic analyses were conducted on 145 individuals from 9 populations using 8 InDel markers. Results indicated a relatively high level of within-population genetic diversity (He = 0.35) and limited among-population differentiation (FPT = 0.20) for this predominantly self-pollinating grass. UPGMA cluster analyses, PCoA and Bayesian clustering supported the demarcation of the populations into 3 groups that were not correlated with location or altitude, suggesting a loose genetic affinity of B. hybridum populations in relation to their geographical locations, and no obvious genetic structure among populations across the study area. This pattern was associated with a considerable amount of an asymmetric gene flow between populations. Overall, the obtained results suggest that the long-distance seed-dispersal is the most important factor in shaping the spatial genetic structure of B. hybridum in Tunisia. They also provide key guidelines for on-going and future work including breeding programs and genome-wide association studies