Accurate Prediction and Validation of Response to Endocrine Therapy in Breast Cancer

Abstract

A four-gene predictive model of clinical response to AIs by 2 weeks has been generated and validated. Deregulated immune and apoptotic responses before treatment and cell proliferation that is not reduced 2 weeks after initiation of treatment are functional characteristics of breast tumors that do not respond to AIs.

The role of steroid hormones in breast cancer stem cells

“…Endocrine sensitivity can partly be predicted by serial analysis of the proliferation marker Ki67 expression in pre-surgical 'window' studies or longer term neoadjuvant studies of several months of treatment (Dowsett et al 2011). More recently, a four-gene signature including genes related to immune signalling (IL6ST), apoptosis (NGFRAP1), and proliferation (ASPM and MCM4) was reported to predict the clinical response of patients treated with AIs (Turnbull et al 2015). However, despite the undoubted success of tamoxifen (or similar endocrine) treatment, at least half of patients with micrometastatic disease will relapse despite therapy, often many years after initial surgery and endocrine therapy is completed (Early Breast Cancer Trialists' Collaborative Group et al 2011).…”

Adaptation to AI Therapy in Breast Cancer Can Induce Dynamic Alterations in ER Activity Resulting in Estrogen-Independent Metastatic Tumors

“…Statistical analyses were conducted using STATA 10 data analysis software (Stata Corp. LP) and GraphPad Prism 6 (GraphPad software Inc.), and values of P < 0.05 were considered significant. Changes in gene expression on AI treatment and association with outcome were determined from the Edinburgh dataset of 72 patients treated with letrozole, performed on Affymetrix and Illumina microarrays with batch correction (34,35). The Kaplan-Meier analysis was performed using the R Survival package.…”

“…Here, we Maintained expression of steroid-dysregulated genes following AI treatment associates with poor outcomes. A, tumors were sampled before, during, and after neoadjuvant AI therapy (34,38) as illustrated. B, box plots display expression changes of steroid-dysregulated genes in neoadjuvant AI-treated patients (n ¼ 50 patients).…”

“…In the patient setting, the clinical significance of the gene response to neoadjuvant AI therapy was examined in an extended cohort of 72 paired tumor biopsies with 10-year follow-up data (published datasets GSE20181, GSE55374, and GSE59515; ref. 34). The inability of AI therapy to inhibit the expression of the ERdysregulated gene set was significantly associated with poor response to therapy.…”

Diverse biology of breast cancer: search for adequate treatment

“…Известно, что циклин-зависимые киназы (CDK 4/5) контролируют рост ER+(позитивные) РМЖ. В таблице 2 представлены молекулярные «мишени» резистентности к гормонотерапии и проводимые или завершенные кли-нические испытания ингибиторов этих мишеней с целью преодоления механизма резистентности [11,12,13,14,15,16,17]. Рассмотрим другую важнейшую модель, определяющую высокую агрессивность заболевания, приводившего рань-ше (до разработки моноклональных антител к HER2) к ги-бели большинство пациентов с HER2+ РМЖ.…”