Search

MicroRNA-27a-5p (miR-27a-5p) has been closely related to the pathogenesis of different solid tumors, showing potentials as both useful biomarker and druggable target of clinical application. In our study, we performed the expression analysis of miR-27a-5p in a retrospective cohort of 232 breast cancer (BC) patients with a median follow-up of 99.4 months enrolled according to the REMARK guidelines. Of those patients, 9 showed synchronous metastases (MTX), 45 developed metastases during the follow-up time (M0>M1), and 178 were free from metastases after a follow-up of at least 5 years (M0). As controls, 13 normal breast tissues (NBTs) from reductive mammoplasty and 11 pre-invasive breast lesions (PreBr) were also profiled. Overall, miR-27a-5p showed higher levels in NBTs (Median 2.28, IQR 1.50-5.40) and pre-invasive breast lesions (Median 3.32, IQR 1.68-4.32) compared to tumour samples. In particular, miR-27a-5p was less expressed in patients with synchronous (Median 1.03 IQR 0.83-1.58) or metachronous (Median 1.83, IQR 1.29-3.17) metastases than in patients free from metastases after a 5-year follow-up (Median 2.17, IQR 1.19-3.64). Thus, we found that miR-27a-5p expression (log values) is negatively correlated with breast pathology evolution (R= -0.13, P=0.038). Next, we assessed the potentialities of miR-27a-5p as BC-specific prognostic biomarker in the subgroup of patients without metastases at diagnosis (n=222). Moreover, increased miR-27a-5p levels were associated with reduced risk of disease progression (Progression Free Survival (PFS) HR 0.43, 95%CI 0.18-0.99, P=0.048), metastases development (Metastases Free survival (MFS) HR 0.42, 95%CI 0.18-0.96, P=0.039), and cancer-related death (Overall Survival (OS) HR 0.30, 95%CI 0.12-0.74, P=0.009) in the subgroup of HER2-amplified tumours (n=26). Then, we extended our analysis to the TCGA BRCA dataset by selecting a total of 561 cases without synchronous metastases, for whom miR-27a-5p expression levels, and clinical and follow-up data were available. Among them, 19 were HER2 amplified according to clinical guidelines (i.e. score 3+ at immunostaining or FISH-positive). Similarly to our internal cohort, high miR-27a-5p was associated to reduced risk of disease progression (PFS HR 0.61, 95%CI 0.10-3.61) and death (OS HR 0.62, 95%CI 0.08-5.05) in the subgroup of HER2-amplified cases, although the association did not reach statistical significance. Overall, our data support the tumour suppressive role of miR-27a-5p in breast cancer, and suggest miR-27a-5p as putative prognostic biomarker in HER2-amplified tumours. Citation Format: Barbara Pasculli, Andrea Fontana, Serena Barile, Morritti Maria, Luigi Ciuffreda, Paolo Graziano, Evaristo Maiello, Paola Parrella. Hsa-miR-27a-5p expression in breast cancer and its association with patient outcome [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1492.

Fundació Carreras This work was supported by Italian Ministry of Health (MoH) TRANSCAN Joint Transnational Call (JTC) 2013 co-funded by the European Regional Development Fund, "A way of making Europe" RRC-2014-2354565, Italian Ministry of Health (MoH) "Ricerca Corrente 2019" and "5×1000″ voluntary contributions" and partially supported by Associazione Italiana Ricerca sul Cancro (AIRC) Project Code: 16747. While the molecular functions of miR-200 family have been deeply investigated, a role for these miRNAs as breast cancer biomarkers remains largely unexplored. In the attempt to clarify this, we profiled the miR-200 family members expression in a large cohort of breast cancer cases with a long follow-up (H-CSS cohort) and in TCGA-BRCA cohort. Overall, miR-200 family was found upregulated in breast tumors with respect to normal breast tissues while downregulated in more aggressive breast cancer molecular subtypes (i.e. Luminal B, HER2 and triple negative), consistently with their function as repressors of the epithelial-to-mesenchymal transition (EMT). In particular miR-141-3p was found differentially expressed in breast cancer molecular subtypes in both H-CSS and TCGA-BRCA cohorts, and the combined analysis of all miR-200 family members demonstrated a slight predictive accuracy on H-CSS cancer specific survival at 12 years (survival c-statistic: 0.646; 95%CI 0.538-0.754).

Irradiation-induced sarcomas are a late sequelae of irradiation therapy. Most sarcomas have been reported to occur after exposure to a radiation dose of 55 Gys and above, with a dose ranging from 16 Gys to 112 Gys. These tumours are very aggressive and an early detection is needed for a timely intervention. Surgery is only effective treatment for local control instead chemotherapy is a valuable tool for systemic control of disease. Irradiation therapy use is controversial because of its side effects on a site previously irradiated. Irradiation therapy combined with hyperthermia is a new treatment that overcomes these problems without limiting the effect of radiation therapy. It may become a tool for local control of the unresectable tumours or an adjuvant treatment of the surgery. In this report we present a rare case of irradiation-induced recurrent osteosarcoma involving the chest wall that was treated with surgical resection followed by radiation therapy combined with hyperthermia as an adjuvant treatment of the surgery.

miR-9 (hsa-miR-9-5p, miR-9-5p) is a highly conserved microRNA (miRNA) primarily expressed in the central nervous system. The three promoters of miR-9 (miR-9-1 at 1q22, miR-9-2 at 5q14.3 and miR-9-3 at 15q26.1) are embedded within CpG islands, and hypermethylation in at least one of these regions has been reported in several tumor types, thus miR-9-5p has been designated as an epigenetically regulated miRNA. However, only a partial or none correlation between methylation status of miR-9 loci and miR-9-5p expression has been demonstrated so far. Furthermore, the expression levels of miR-9-5p resulted highly variable across different carcinomas and conflicting evidences also exist about its functional role within the tumor context. In light of this, we took the effort of clarifying the role of miR-9-5p in primary breast cancer tissues and of evaluating its potential as clinical relevant prognostic biomarker. We analysed miR-9-5p expression and miR-9 promoters methylation status in 129 breast cancer cases and 12 normal breast tissues (NBTs), by qRT-PCR and MSP respectively. Overall, miR-9-5p was increased in tumors compared to NBTs (P Citation Format: Raffaela Barbano, Barbara Pasculli, Michelina Rendina, Andrea Fontana, Caterina Fusilli, Massimiliano Copetti, Stefamo Castellana, Vanna Maria Valori, Maria Morritti, Paolo Graziano, Luigi Ciuffreda, Michelina Coco, Francesco Picardo, Tommaso Mazza, Ella Evron, Roberto Murgo, Evaristo Maiello, Manel Esteller, Vito Michele Fazio, Paola Parrella. miR-9-5p expression in breast cancer correlates with hormone receptor status and affects patients survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4734. doi:10.1158/1538-7445.AM2017-4734

We have recently demonstrated that the evaluation of miR10b expression relative to its normal counterparts (Relative Expression Ratio, RER) is able to predict patients risk to develop distant metastases. To confirm these results and evaluate whether other microRNAs could be predictive of outcome in breast cancer we evaluated the expression of miR10b and miR9 in paired tumors and apparently normal breast tissues 2 cm distant from tumour (NBT) on an extended cohort (n = 127) with a longer follow up (median 42 months). As control normal breast tissues from 10 healthy subjects (HBT) treated by reductive mammoplasty were analyzed. An increased expression was seen for the miR9 and miR10b in NBT samples as compared with HBT (P Citation Format: Raffaela Barbano, Barbara Pasculli, Massimiliano Copetti, Andrea Fontana, Michelina Coco, Lorenzo Vitulano, Maria Luana Poeta, Francesca Picardo, Gianfranco Marangi, Roberto Murgo, Luigi Ciuffreda, Vanna Maria Valori, Vanna Maria Valori, Maria Morritti, Evaristo Maiello, Vito Michele Fazio, Paola Parrella. Evaluation of miR10b and miR9 expression in breast cancer and correlations with distant metastases development. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3977. doi:10.1158/1538-7445.AM2015-3977

Aim: Six months FOLFOX4 or XELOX is the standard adjuvant chemotherapy in radically resected stage III colon cancer, however a shorter duration of therapy could be equally efficacious. Methods: This is an Italian, multicenter, non-inferiority phase III trial randomizing patients (pts) with stage III and high risk stage II colon cancer to receive 3 (arm 3) vs 6 (arm 6) months of FOLFOX4 or XELOX. Primary end-point is relapse free survival (RFS), and the arm 3 will be considered non-inferior if the superior margin of the 95% CI of the HR is Results: From June 2007 to March 2013, 3,759 patients were accrued and 3,738 (1860 in arm 3 and 1878 in arm 6) included in the intent-to-treat (ITT) population, since 21 pts were excluded due to major violations. The proportion of FOLFOX4 vs XELOX was 64% vs 36% in both arms. Among the ITT population, demographic factors (including gender and age) were balanced in the two arms. As expected, compliance was higher in arm 3 than in arm 6: treatment completion rate without any modification of planned dose and timing was 35% in arm 3 and 12% in arm 6, while approximately 55% pts in both arms completed treatment with modifications of dose and/or timing, resulting in 90% vs 67% pts receiving all the planned cycles. Therapy was permanently interrupted due to toxicity in 5% of pts in arm 3 and 17% in arm 6. The overall incidence of grade 3-4 toxicity (including grade 2 oxaliplatin neurotoxicity) events was 37% in arm 3 and 60% in arm 6. Grade 2+ neuropathy was more frequent in arm 6 than in arm 3: 32 % vs 9%, respectively. With a median follow-up of 30 months, 476 pts relapsed, 195 died and 520 relapsed and/or died. Conclusions: TOSCA is the first trial completing the accrual among the international initiative of comparing 3 vs 6 months of adjuvant treatment in colon cancer (IDEA). In general, reported toxicity was low, but, as expected, significantly higher in the 6-month arm compared to that of the 3-month arm; accordingly, compliance was lower in the standard 6-month arm. Data for efficacy analysis are premature. Disclosure: All authors have declared no conflicts of interest.