Working together for the family: HER oncogenes co-amplification in breast cancer

LAURITO SERGIO; BRANHAM MARIA T; CAMPOY, EMANUEL; REAL, SEBASTIAN; CUETO, JUAN ; GAGO, FRANCISCO; GLATSTEIN TELMA; DE LA IGLESIA P; ROQUÉ MARIA

Simposio; BUENOS AIRES BREAST CANCER SYMPOSIUM; 2021

HER2 overexpressing tumors represent 15-20% of invasiveductal breast carcinomas (IDC). Even though they aretreated with the monoclonal antibody trastuzumab, 20%of primary and 70% of metastatic HER2 tumors developresistance. HER2 belongs to a 4-member oncogene family(HER1-4), which present the capacity to compensateinhibition. We believe it is relevant to know the state ofthe whole family to predict response to treatment. Here wehave designed a probe mix to detect the amplification ofthe 4 HER oncogenes. One hundred and eleven IDC (54fresh frozen and 57 FFPE) were analyzed by MLPA, andHER2 determination was validated prospectively by FISH,IHC and CISH (Pearson r = 0.95; 0.59; 0.97 respectively, p< 0.0001). Positive correlation between CNV and expressionwas observed in wet and in-silico analyses for the 4oncogenes (Spearman Rank test p < 0.05). Of the 111included samples, 26.12% presented at least one HERamplified, of which 23.07% showed co-amplifications.In addition, we developed a protocol based on MLPAddPCR,which allows the detection of the tumor proportionof co-amplified HER. In this case, MLPA reactions wereperformed on single cells using Taqman probes, and thenanalyzed by ddPCR. By this, we detected intra-tumor heterogeneityfor HER co-amplifications. Here we present 2tools based in MLPA that can identify the co-amplificationlevel and the intra tumor heterogeneity of the 4 HER oncogenes,contributing to the precision medicine of breastcancer patients.