Browsing by Author "El-Abed, S"

Filter results by typing the first few letters
Now showing 1 - 2 of 2
  • No Thumbnail Available
    Publication
    End-of-neoadjuvant treatment circulating microRNAs and HER2-positive breast cancer patient prognosis: An exploratory analysis from NeoALTTO
    (Frontiers Media S.A., 2023) Di-Cosimo, S; Ciniselli, CM; Pizzamiglio, S; Cappelletti, V; Silvestri, M; El-Abed, S; Izquierdo, M; Bajji, M; Nuciforo, P; Huober, J; Cameron, D; Chia, S; Gomez, HL; Iorio, MV; Vingiani, A; Pruneri, G; Verderio, P
    Background: The absence of breast cancer cells in surgical specimens, i.e., pathological complete response (pCR), is widely recognized as a favorable prognostic factor after neoadjuvant therapy. In contrast, the presence of disease at surgery characterizes a prognostically heterogeneous group of patients. Here, we challenged circulating microRNAs (miRNAs) at the end of neoadjuvant therapy as potential prognostic biomarkers in the NeoALTTO study. Methods: Patients treated within the trastuzumab arm (i.e., pre-operative weekly trastuzumab for 6 weeks followed by the addition of weekly paclitaxel for 12 weeks; post-operative FEC for 3 cycles followed by trastuzumab up to complete 1 year of treatment) were randomized into a training (n= 54) and testing (n= 72) set. RT-PCR-based high-throughput miRNA profile was performed on plasma samples collected at the end of neoadjuvant treatment of both sets. After normalization, circulating miRNAs associated with event free survival (EFS) were identified by univariate and multivariate Cox regression model. Results: Starting from 23 circulating miRNAs associated with EFS in the training set, we generated a 3-circulating miRNA prognostic signature consisting of miR-185-5p, miR-146a-5p, miR-22-3p, which was confirmed in the testing set. The 3-circulating miRNA signature showed a C-statistic of 0.62 (95% confidence interval [95%CI] 0.53-0.71) in the entire study cohort. By resorting to a multivariate Cox regression model we found a statistical significant interaction between the expression values of miR-194-5p and pCR status (p.interaction =0.005) with an estimate Hazard Ratio (HR) of 1.83 (95%CI 1.14- 2.95) in patients with pCR, and 0.87 (95%CI 0.69-1.10) in those without pCR. Notably, the model including this interaction along with the abovementioned 3-circulating miRNA signature provided the highest discriminatory capability with a C-statistic of 0.67 (95%CI 0.58-0.76). Conclusions: Circulating miRNAs are informative to identify patients with different prognosis among those with heterogeneous response after trastuzumab-based neoadjuvant treatment, and may be an exploitable tool to select candidates for salvage adjuvant therapy. Copyright © 2023 Di Cosimo, Ciniselli, Pizzamiglio, Cappelletti, Silvestri, El-Abed, Izquierdo, Bajji, Nuciforo, Huober, Cameron, Chia, Gomez, Iorio, Vingiani, Pruneri and Verderio.
  • Thumbnail Image
    Publication
    Final analysis of the ALTTO trial: adjuvant trastuzumab in sequence or in combination with lapatinib in patients with HER2-positive early breast cancer [BIG 2-06/NCCTG N063D (Alliance)]
    (Elsevier B.V., 2024) de, Azambuja, E; Piccart-Gebhart, M; Fielding, S; Townend, J; Hillman, DW; Colleoni, M; Roylance, R; Kelly, CM; Lombard, J; El-Abed, S; Choudhury, A; Korde, L; Vicente, M; Chumsri, S; Rodeheffer, R; Ellard, SL; Wolff, AC; Holtschmidt, J; Lang, I; Untch, M; Boyle, F; Xu, B; Werutsky, G; Tujakowski, J; Huang, C-S; Baruch, NB; Bliss, J; Ferro, A; Gralow, J; Kim, S-B; Kroep, JR; Krop, I; Kuemmel, S; McConnell, R; Moscetti, L; Knop, AS; van, Duijnhoven, F; Gomez, H; Cameron, D; Di, Cosimo, S; Gelber, RD; Moreno-Aspitia, A
    Background: Dual anti-human epidermal growth factor receptor 2 (HER2) blockade has improved the outcomes of patients with early and metastatic HER2-positive breast cancer. Here we present the final 10-year analysis of the ALTTO trial. Patients and methods: The ALTTO trial (NCT00490139) is a prospective randomized, phase III, open-label, multicenter study that investigated the role of adjuvant chemotherapy and trastuzumab alone, in combination or sequentially with lapatinib. The primary endpoint was disease-free survival (DFS) and secondary endpoints included overall survival (OS), time to distant recurrence and safety. Results: Overall, 6281 patients with HER2-positive early breast cancer were included in the final efficacy analysis in three treatment groups: trastuzumab (T), lapatinib + trastuzumab (L + T) and trastuzumab followed by lapatinib (T→L). Baseline characteristics were well balanced between groups. At a median follow-up of 9.8 years, the addition of lapatinib to trastuzumab and chemotherapy did not significantly improve DFS nor OS. The 10-year DFS was 77% in T, 79% in L + T and 79% in T→L, and the 10-year OS was 87%, 89% and 89%, respectively. The incidence of any cardiac event was low and similar in the three treatment groups. Conclusions: With a longer follow-up, no significant improvement was observed in DFS in patients treated with dual anti-HER2 blockade with lapatinib + trastuzumab compared to trastuzumab alone. The 10-year survival rates for the combination group are consistent with other studies that have explored dual anti-HER2 therapy.