Genomic Instability and

Although aromatase inhibitor (AI) treatment is effective in estrogen receptor-positive postmenopausal breast cancer, resistance is common and incompletely explained. Genomic instability, as measured by somatic copy number alterations (SCNAs), is important in breast cancer development and prognosis. SCNAs to specific genes may drive intrinsic resistance, or high genomic instability may drive tumor heterogeneity, which allows differential response across tumors and surviving cells to evolve resistance to treatment rapidly. We therefore evaluated the relationship between SCNAs and intrinsic resistance to treatment as measured by a poor antiproliferative response. SCNAs were determined by single nucleotide polymorphism array in baseline and surgery core-cuts from 73 postmenopausal patients randomly assigned to receive 2 weeks of preoperative AI or no AI in the Perioperative Endocrine Therapy-Individualizing Care (POETIC) trial. Fifty-six samples from the AI group included 28 poor responders (PrRs, less than 60% reduction in protein encoded by the  Genomic instability correlated with Ki-67 expression at both baseline ( We observed that primary tumors with high genomic instability have an intrinsic resistance to AI treatment and do not require additional evolution to develop resistance to estrogen deprivation therapy.

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© 2019 by American Society of Clinical Oncology.

Déclaration de conflit d'intérêts

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/po/author-center. Pascal GellertEmployment: BioNTechMaggie Chon U. CheangPatents, Royalties, Other Intellectual Property: Patent for breast cancer classifier: US Patent No. 9,631,239 with royalties paidJames MordenResearch Funding: Pfizer (Inst) Travel, Accommodations, Expenses: PfizerJudith M. BlissResearch Funding: AstraZeneca (Inst), Merck Sharp & Dohme (Inst), Medivation (Inst), Puma Biotechnology (Inst), Clovis Oncology (Inst), Pfizer (Inst), Janssen-Cilag (Inst), Novartis (Inst), Roche (Inst) Travel, Accommodations, Expenses: PfizerIan SmithHonoraria: Roche, Eisai, AstraZeneca, Genomic Health, Pfizer Consulting or Advisory Role: Roche, AstraZeneca, Eisai, Pfizer, Genomic Health Travel, Accommodations, Expenses: Roche, PfizerMitch DowsettHonoraria: Myriad Genetics Consulting or Advisory Role: GTx, Radius Health, Orion Research Funding: Pfizer (Inst), Radius Health (Inst) Travel, Accommodations, Expenses: Pfizer, Myriad Genetics Other Relationship: Institute of Cancer Research No other potential conflicts of interest were reported.