American Association for Cancer Research
10780432ccr211317-sup-263743_2_supp_7247340_qw4jpp.pdf (199.5 kB)

Table S1, S2, S3, S4 from Copy Number Aberration Analysis to Predict Response to Neoadjuvant Anti-HER2 Therapy: Results from the NeoALTTO Phase III Clinical Trial

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journal contribution
posted on 2023-03-31, 22:51 authored by David Venet, Mattia Rediti, Marion Maetens, Debora Fumagalli, David N. Brown, Samira Majjaj, Roberto Salgado, Lajos Pusztai, Nadia Harbeck, Sarra El-Abed, Yingbo Wang, Cristina Saura, Henry Gomez, Vladimir Fedorovich Semiglazov, Evandro de Azambuja, Jens Huober, Paolo Nuciforo, Serena Di Cosimo, Martine Piccart, Sherene Loi, Françoise Rothé, Christos Sotiriou

Table S1: Clinicopathological characteristics of the patients. Table S2: List of 49 genes associated with CNAs in breast cancer from the COSMIC Cancer Gene Census database. Table S3: Gene ontology analysis of the genes correlated with the genome instability index. Table S4: Gene ontology analysis of the genes anti-correlated with the genome instability index.



The heterogeneity of response to anti-HER2 agents represents a major challenge in patients with HER2-positive breast cancer. To better understand the sensitivity and resistance to trastuzumab and lapatinib, we investigated the role of copy number aberrations (CNA) in predicting pathologic complete response (pCR) and survival outcomes in the NeoALTTO trial. The neoadjuvant phase III NeoALTTO trial enrolled 455 patients with HER2-positive early-stage breast cancer. DNA samples from 269 patients were assessed for genome-wide copy number profiling. Recurrent CNAs were found with GISTIC2.0. CNA estimates were obtained for 184 patients included in NeoALTTO. Among those, matched transcriptome and whole-exome data were available for 154 and 181 patients, respectively. A significant association between gene copy number and pCR was demonstrated for ERBB2 amplification. Nevertheless, ERBB2 amplification ceased to be predictive once ERBB2 expression level was considered. GISTIC2.0 analysis revealed 159 recurrent CNA regions. Lower copy number levels of the 6q23-24 locus predicted absence of pCR in the whole cohort and in the estrogen receptor–positive subgroup. 6q23-24 deletion was significantly more frequent in TP53 wild-type (WT) compared with TP53-mutated, resulting in copy number levels significantly associated with lack of pCR only in the TP53 WT subgroup. Interestingly, a gene-ontology analysis highlighted several immune processes correlated to 6q23-24 copy number. Our analysis identified ERBB2 copy number as well as 6q23-24 CNAs as predictors of response to anti–HER2-based treatment. ERBB2 expression outperformed ERBB2 amplification. The complexity of the 6q23-24 region warrants further investigation.

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