2018 ASCO Annual Meeting!
Session: Breast Cancer—Local/Regional/Adjuvant
Type: Poster Session
Time: Saturday June 2, 8:00 AM to 11:30 AM
Location: Hall A
Next-generation targeted sequencing (NGTS) investigating CDK4 as a prognostic driver in pure invasive lobular breast carcinoma (ILC): Preliminary results in early-stage patients (pts) stratified according to a validated clinico-pathological model.
2018 ASCO Annual Meeting
Poster Board Number:
Poster Session (Board #34)
J Clin Oncol 36, 2018 (suppl; abstr 542)
Author(s): Luisa Carbognin, Michele Simbolo, Caterina Vicentini, Isabella Sperduti, Anna Caliò, Francesco Schettini, Maria Vittoria Dieci, Gaia Griguolo, Sara Pilotto, Rolando Nortilli, Giovanni Paolo Pollini, Grazia Arpino, Valentina Guarneri, Sabino De Placido, Pier Franco Conte, Erminia Manfrin, Matteo Brunelli, Aldo Scarpa, Giampaolo Tortora, Emilio Bria; University of Verona, Verona, Italy; Department of Diagnostics and Public Health, Section of Anatomical Pathology and ARC-Net Research Centre, University and Hospital Trust of Verona, Verona, Italy; Bio-Statistics Unit, Regina Elena National Cancer Institute, Rome, Italy; Department of Pathology, AOUI, Verona, Verona, Italy; University of Naples Federico II, Naples, Italy; University of Padova and Istituto Oncologico Veneto IRCCS, Padua, Italy; University of Padova, Padua, Italy; Medical Oncology, University of Verona, Verona, Italy; Surgery d.U, AOUI, Verona, Italy; Clinical Medicine and Surgery Department, University of Naples Federico II, Naples, Italy; Department of Surgery, Oncology and Gastroenterology, University of Padua, Medical Oncology 2, Instituto Oncologico Veneto IRCCS, Padova, Italy; University of Padova and Istituto Oncologico Veneto IRCSS, Padova, Italy; Pathology d.U, AOUI, Verona, Italy; Department of Pathology and Diagnostic, Azienda Ospedaliera Universitaria Integrata (AOUI) and University of Verona, Verona, Italy; U.O.C. Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy
Background: The aim of this analysis was to investigate the distribution of molecular abnormalities and their potential role as therapeutic targets (with particular regard to CDK4/6 alterations) in resected ILC pts, grouped according to prognosis. Methods: Clinico-pathological multi-center data of early-stage pure ILC pts were correlated to disease-free survival (DFS). A continuous score was derived according to multivariate Hazard Ratios, to develop a 3-class model. The model was validated in an external pts’ cohort. Mutational and Copy Number Variation (CNV) analyses by NGTS, including 26 genes, were performed for pts at Poor and Good Prognosis (PP/GP). Quantitative-PCR analysis was applied for CNV validation; IHC for CDK6 was accomplished. Fisher’s exact test and Peto Odds Ratio (OR) were adopted for comparison. Results: Data from 773 pts (Training/Validation Set [TS/VS]: 491/282) were gathered. At multivariate analysis, T-size and N-status were independent predictors for DFS. A significant difference between pts at low/intermediate/high risk was found (10-yrs DFS: 76.3%/67.6%/39.8%, respectively, p < 0.0001) in the TS. The model discriminated DFS in the VS (p < 0.0001). According to the developed model, 20 PP and 14 GP pts underwent molecular analysis. In PP group, CDH1 was the most mutated gene (50.0%) followed by PIK3CA (35.0%). MAP3K1 (10.0%), ERBB2 and PTEN were mutated with low frequency (6.1%), only in the PP group. With regard to CNV, CDH1 loss (55.0%) were the most frequent event, followed by gain in ESR1, FGFR1 and CDK4 (35.0%), which was present exclusively in PP group (p = 0.03) and validated by quantitative-PCR. Moreover, CDK4 gain reported a significant higher chance to be associated with PP (OR = 7.98, 95%CI 1.51-42.1, p = 0.014). CDK6 overexpression showed a trend toward an association with PP (OR = 3.29, 95%CI 0.56-19.25, p = 0.18). Conclusions: These preliminary data first suggest that CDK4 gain is potentially associated with PP. The potential druggable of this alteration deserves further clinical investigations in the context of ILC.
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