Abstract 172P
Background
A substantial minority of EBC pts relapse despite pCR after neoadjuvant therapy. We compared gene expression between primary tumors of pts with relapse despite pCR and: (i) primary tumors from matched controls with pCR and no relapse (interindividual analysis), or (ii) matched recurrent tumors (intraindividual analysis).
Methods
This retrospective single-center study included 14 pts (8 hormone receptor-positive, 5 HER2+, 5 triple-negative [TN]) with relapse despite pCR (8 distant, 6 locoregional) plus 41 matched controls with pCR and no relapse. To exclude undetected primary metastatic disease, time to distant relapse >12 months was required. RNA from primary and recurrent tumors was analyzed (Breast Cancer 360 panel, nCounter® platform; NanoString). Differential expression of 42 genes/signatures was evaluated as log2 fold-change (logFC) and compared by t test ± false-discovery rate (FDR) adjustment.
Results
Analysis was successful in 68/69 samples. In interindividual analyses of primary tumors, major histocompatibility complex class II expression was lower vs. controls in pts with any relapse (logFC -0.819; P = 0.030) or distant relapse (logFC -1.151; P = 0.013). Primaries with later distant relapse also had lower interferon-γ signaling (logFC -0.759; P = 0.050) and greater homologous recombination deficiency (logFC 0.649; P = 0.026) vs. controls. In subgroup analyses, relapse was associated with higher mammary stemness (logFC 1.716; P = 0.026), progesterone receptor (logFC 1.027; P = 0.027) and endothelial cells (logFC 0.827; P = 0.033) in TN pts, and higher proliferation score (logFC 0.721, P = 0.023) in HER2+ pts. Intraindividual analysis showed androgen receptor upregulation (logFC 1.264, P = 0.046) and downregulation of TIGIT (logFC -1.037, P = 0.040) and estrogen receptor signaling (logFC -0.595, P = 0.022) in recurrent tumors vs. primaries. FDR-adjusted P-values were not significant.
Conclusions
These correlations between gene expression and relapse despite pCR warrant further investigation to identify pts who remain at high risk in this setting, e.g. in future immunotherapy, poly(ADP-ribose) polymerase inhibitor or targeted HER2-enriched trials.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
S. Kümmel: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy: Genomic Health; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy: Celgene; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Daiichi Sankyo; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Somatex; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: PFM Medical; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Sonoscape; Leadership role, Shareholder/Stockholder/Stock options, Partial non-profit ownership: WSG (Westdeutsche Studiengruppe); Leadership role: AGO (Arbeitsgemeinschaft Gynäkologische Onkologie). N. Harbeck: Honoraria (institution): only research grants; Advisory/Consultancy: Agendia; Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy: Celgene; Advisory/Consultancy, Speaker Bureau/Expert testimony: Daiichi Sankyo; Advisory/Consultancy: Genomic Health; Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy: Odonate; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy: Sandoz/Hexal; Advisory/Consultancy: Seattle Genetics; Speaker Bureau/Expert testimony: Amgen; Speaker Bureau/Expert testimony: Nanostring; Leadership role: German AGO Breast Committee; Research grant/Funding (institution): several phase II-III trials; Shareholder/Stockholder/Stock options: Co-Director West German Study Group; Full/Part-time employment: LMU Munich; Spouse/Financial dependant: West German Study Group. P. Schmid: Advisory/Consultancy: Pfizer; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution), Spouse/Financial dependant: Roche; Advisory/Consultancy: Merck; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Bayer; Advisory/Consultancy: Eisai; Advisory/Consultancy: Celgene; Advisory/Consultancy: Puma; Research grant/Funding (institution), Spouse/Financial dependant: Genentech; Research grant/Funding (institution): Oncogenex. J. Cortés: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy: Celgene; Advisory/Consultancy: Cellestia; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: Biothera Pharmaceutical; Advisory/Consultancy: Merus; Advisory/Consultancy: Seattle Genetics; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Daiichi Sankyo; Advisory/Consultancy: Erytech; Advisory/Consultancy: Athenex; Advisory/Consultancy: Polyphor; Honoraria (self), Advisory/Consultancy: Lilly; Advisory/Consultancy: Servier; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck Sharp & Dohme; Advisory/Consultancy: GSK; Advisory/Consultancy: Leuko; Advisory/Consultancy: Bioasis; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: Boehringer Ingelheim; Honoraria (self), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Eisai; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Honoraria (self): Samsung Bioepis; Research grant/Funding (institution): Ariad Pharmaceuticals; Research grant/Funding (institution): Baxalta GMBH/Servier Affaires; Research grant/Funding (institution): Bayer Healthcare; Research grant/Funding (institution): Guardant Health; Research grant/Funding (institution): Piqur Therapeutics; Research grant/Funding (institution): Puma C; Shareholder/Stockholder/Stock options: MedSIR; Research grant/Funding (institution): Queen Mary University of London. C. Seiberling: Travel/Accommodation/Expenses: Teva. B. Ataseven: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Tesaro; Honoraria (self): Celgene; Honoraria (self): Clovis; Honoraria (self): AstraZeneca; Travel/Accommodation/Expenses: PharmaMar. M. Dyson: Advisory/Consultancy: Merck; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Novartis; Advisory/Consultancy: EUSA Pharma; Advisory/Consultancy: AbbVie; Advisory/Consultancy: Janssen; Advisory/Consultancy: Biogen; Advisory/Consultancy: Menarini; Advisory/Consultancy: Norgine. O. Gluz: Advisory/Consultancy, Travel/Accommodation/Expenses: Celgene; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Genomic Health; Advisory/Consultancy: Amgen; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Novartis; Advisory/Consultancy: Lilly; Advisory/Consultancy: Nanostring; Advisory/Consultancy: Eisai; Advisory/Consultancy: MSD; Travel/Accommodation/Expenses: Daiichi Sankyo. M. Reinisch: Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy: AstraZeneca; Travel/Accommodation/Expenses: Pfizer. All other authors have declared no conflicts of interest.