Impact of Duration of Neoadjuvant Aromatase Inhibitors on Molecular Expression Profiles in Estrogen Receptor–positive Breast Cancers

Abstract

Disclosure declarations: M.C.U.C. has a patent for Breast Cancer Classifier: US Patent No. 9,631,239 with royalties paid, is an advisory member of Veracyte and receives research funding from NanoString Technologies. MD receives honoraria from Myriad Genetics and is a consultant and advisory board member of GTx, Radius Health, Orion Pharma, Lilly, Agile and Astrazeneca, has received funding from Pfizer (Inst) and Radius Health (Inst) and has been payed expenses from Pfizer and Myriad Genetics. HT reports a grant from Bayer. JMB reports grants from Cancer Research UK, during the conduct of the study; grants from Medivation; grants and non-financial support from AstraZeneca, Merck Sharp & Dohme, Puma Biotechnology, Clovis Oncology, Pfizer, Janssen-Cilag, Novartis, and Roche, outside the submitted work. The rest of authors declare no potential conflicts of interests. Statement of translational relevance:Our study shows that neoadjuvant treatment with short and longer-term aromatase inhibitors (AI) in primary estrogen receptor (ER+) positive breast cancer (BC) exerts comparable impact on changes in intrinsic subtypes between baseline and surgery. However, neoadjuvant AI treatment beyond 2 weeks leads moreResearch.

Unraveling the clinicopathological and molecular changes induced by neoadjuvant chemotherapy and endocrine therapy in hormone receptor-positive/HER2-low and HER2-0 breast cancer

“…Noteworthy, Bergamino et al. 30 observed a molecular downstaging under AI presurgical treatment that was consistent with our findings. Interestingly, a shift towards less aggressive subtypes and ROR score was also observed in the SOLTI-CORALEEN trial of patients with HR+/HER2-negative disease randomized to receive NACT or NET+CDK4/6-inhibitor ribociclib.…”

Unraveling the clinicopathological and molecular changes induced by neoadjuvant chemotherapy and endocrine therapy in hormone receptor-positive/HER2-low and HER2-0 breast cancer

“…In that same analysis, we observed an encouraging trend towards better survival outcomes associated to such a molecular downstaging 16 . Notably, Bergamino M. et al observed a consistent molecular downstaging under AI presurgical treatment, as well 29 . A shift towards less aggressive subtypes and ROR score was also observed in the SOLTI-CORALEEN trial of patients with HR+/HER2-negative disease randomized to receive NACT or NET+CDK4/6-inhibitor ribociclib 30 .…”

“…Interestingly, Bergamino M. et al also observed significant changes in the expression of immune response/immune-checkpoint components' genes, that were associated with AIresistant tumors 29 . In our cohort, although with a limited number of immune-related genes, namely CD4, CD8A, PDCD1 (PD1) and CD274 (PD-L1), we also observed a significant upregulation, with no differences between HER2-0 and HER2-low disease.…”

Gene expression before and after neoadjuvant chemotherapy or endocrine therapy and survival outcomes in hormone receptor-positive, HER2-negative breast cancer: the NEOENDO study

“…PD1, PD-L1 genes) with both NACT and standard NET emerged. Bergamino et al had previously observed the induction of immune in ltration with a short course of preoperatory aromatase inhibitors [32]. Additionally, the increase in immune-related therapeutic targets (i.e.…”