Project description:Samples were taken from ER+ breast cancer patients treated with neoadjuvant endocrine therapy (letrozole) with or without CDK4/6 inhibitor (ribociclib) at the beginning of treatment, 14 days after starting treatment, or after 180 days. Nuclei were isolated and single-nucleus RNA sequencing (snRNA-seq) was performed using 10X or iCell8 technologies.
Project description:Biopsies were collected from post-menopausal women with ER+ HER2- breast cancer who were subsequently treated with either letrozole or letrozole plus bevacizumab.
Project description:We identified a 17-gene Her2-enriched tumor initiating cell (HTIC) signature in MMTV-Her2/Neu mouse mammary TICs. Here, we show that patients with HTICS+ HER2+:ERα− tumors are more likely to achieve a pathologic complete response to trastuzumab-based neoadjuvant chemotherapy compared with HER2+:ER+ tumors. Neoadjuvant study of 50 HER2-positive breast cancer cases treated with trastuzumab-based chemotherapy pre-operatively. Pre-treatment FNA from primary tumors were obtained and RNA extracted and hybridized to Affymetrix microarrays according to manufacturer protocol. Pathologic response was assessed at the end of neoadjuvant treatment.
Project description:Purpose Aromatase inhibitors (AIs) have an established role in breast cancer treatment. Response rates are only 50-70% in the neoadjuvant setting and lower in advanced disease. Accurate biomarkers are urgently needed to predict response in these settings and to determine which individuals will benefit from adjuvant AI therapy. Participants and Methods Pre- and on-treatment (after 2 weeks and 3 months) biopsies were obtained from 89 post-menopausal women with ER+ breast cancer receiving neoadjuvant letrozole for transcript profiling. Dynamic clinical response was assessed by three-dimensional ultrasound measurements. Results The molecular response to letrozole was characterised and a four gene classifier of clinical response was established (accuracy of 96%) based upon the level of two genes prior to treatment (one associated with immune signalling, IL6ST and the other with apoptosis, NGFRAP1) and two proliferation genes (ASPM, MCM4) at 2 weeks of therapy. The four gene signature was found to be 91% accurate in a blinded, completely independent validation dataset of patients treated with anastrozole. Matched 2 week on-treatment biopsies improved predictive power over pre-treatment biopsies alone. This signature also significantly predicted recurrence free survival (p=0.029) and breast cancer specific survival (p=0.009). We demonstrate that the test can also be performed using quantitative PCR or immunohistochemistry. Conclusion A four gene predictive model of clinical response to AIs by two weeks has been generated and validated. Deregulated immune and apoptotic responses before treatment and a failure to reduce proliferation by 2 weeks are functional characteristics of breast tumours that do not respond to AIs. 25 Pre treatment, 25 two week and 25 three month on-treatment primary breast tumour samples from the same patients. Data was analysed with two previously generated datasets, GSE55374 which was also processed on Illumina HT-12v4 BeadChips (GPL10558) and GSE20181 on Affymetrix U133A GeneChips (GPL96)
Project description:Diagnostic samples from female breast cancer patients with ER-positive and HER2-normal tumors selected for neoadjuvant chemotehrapy.
Project description:This study focused on patients with estrogen receptor positive/human epidermal growth factor receptor 2 positive (ER+/HER2+) breast cancer treated with neoadjuvant chemotherapy and HER2-targeted therapy (NAC+H), and was designed to identify novel biomarkers by correlating gene expression, histology and immunohistochemistry with pathologic response. We performed gene expression profiling on 11 pre-treatment tumors samples: 5 who had no or minimal residual disease residual cancer burden (RCB) score of 0 or 1 and 6 who had significant residual disease (RCB score of 2 or 3). ER2/HER2 postive breast tumors biopsied before neoadjuvant chemotherapy were selected to identify potential biomarkers of pathological complete response (pCR)
