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Genomic profiling of the residual disease of advanced high‐grade serous ovarian cancer after neoadjuvant chemotherapy
Author(s) -
Lee Yong J.,
Kim Dachan,
Shim Jung E.,
Bae SuJin,
Jung YuJin,
Kim Sora,
Lee Hanna,
Kim So H.,
Jo Su B.,
Lee JungYun,
Kim HyunSoo,
Paik Soonmyung
Publication year - 2019
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.32729
Subject(s) - serous ovarian cancer , chemotherapy , serous fluid , ovarian cancer , oncology , medicine , disease , cancer research , pathology , cancer
The goal of our study was to demonstrate the spectrum of genomic alterations present in the residual disease of patients with advanced high‐grade serous ovarian cancer (HGSOC) after neoadjuvant chemotherapy (NAC), including matched pretreatment biopsies. During the study period between 2006 and 2017, we collected pre‐NAC and post‐NAC tumor tissue samples from patients with advanced HGSOC. We performed combined next‐generation sequencing and immunohistochemistry to identify actionable targets and pathway activation in post‐NAC residual tumors. We also examined whether post‐NAC profiling of residual HGSOC identified targetable molecular lesions in the chemotherapy‐resistant component of tumors. Among 102 post‐NAC samples, 41 (40%) of patients had mutations in homologous recombination repair (HRR) genes (HRR deficiency). Patients with HRR mutations had higher tumor mutation burdens ( p < 0.001) and higher alterations in the PI3K–AKT–mTOR pathway ( p = 0.004) than patients without these HRR mutations. Nevertheless, we found no significant differences in progression‐free survival ( p = 0.662) and overall survival (OS; p = 0.828) between the two groups. Most patients (91%) had alterations in at least one of the targetable pathways, and those patients with cell cycle ( p = 0.004) and PI3K–AKT–mTOR signaling ( p = 0.005) pathway alterations had poorer OS (Bonferroni‐corrected threshold = 0.0083, 0.05/6). We showed the genomic landscape of tumor cells remaining in advanced HGSOC after NAC. Once validated, these data can help inform biomarker‐driven adjuvant studies in targeting residual tumors to improve the outcomes of patients with advanced HGSOC after NAC.