American Association for Cancer Research
00085472can140620-sup-127369_1_supp_2509400_n6wmzs.xlsx (113.46 kB)

Data Supplement from Molecular Changes in Lobular Breast Cancers in Response to Endocrine Therapy

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posted on 2023-03-30, 22:50 authored by Laura M. Arthur, Arran K. Turnbull, Victoria L. Webber, Alexey A. Larionov, Lorna Renshaw, Charlene Kay, Jeremy S. Thomas, J. Michael Dixon, Andrew H. Sims

Microsoft Excel workbook containing the following gene lists and information; A) 500 most variable genes from Figure 1D, B) differentially expressed genes between ILC and IDC at baseline and 3 months of treatment using Rank Products with a cut-off of 0.05 PFP figure 2, C) differentially expressed genes after 3 months of letrozole in ILC and IDCILC tumors using pairwise Rank Products with a cut-off of 0.05 PFP (percent false positive) from figure 3, D) genes from Sikora et al. 2014 [5] that were represented in the combined Affymetrix/Illumina dataset, E) Additional sample information including the NCBI GEO Accession numbers of the Affymetrix data.



Invasive lobular carcinoma (ILC) accounts for approximately 10% to 15% of breast carcinomas, and although it responds poorly to neoadjuvant chemotherapy, it appears to respond well to endocrine therapy. Pre- and on-treatment (after 2 weeks and 3 months) biopsies and surgical samples were obtained from 14 postmenopausal women with estrogen receptor–positive (ER+) histologically confirmed ILC who responded to 3 months of neoadjuvant letrozole and were compared with a cohort of 14 responding invasive ductal carcinomas (IDC) matched on clinicopathologic features. RNA was extracted and processed for whole human genome expression microarray. Dynamic clinical response was assessed using periodic three-dimensional ultrasound measurements performed during treatment and defined as a reduction of >70% in tumor volume by 3 months. Pretreatment profiles of ILC and IDC tumors showed distinctive expression of genes associated with E-cadherin signaling, epithelial adhesion, and stromal rearrangement. The changes in gene expression in response to letrozole were highly similar between responding ILC and IDC tumors; genes involved in proliferation were downregulated and those involved with immune function and extracellular matrix remodeling were upregulated. However, molecular differences between the histologic subtypes were maintained upon treatment. This is the first study of molecular changes in ILC in response to endocrine therapy to date. The genes that change on letrozole are highly consistent between ILC and IDC. Differences in gene expression between ILC and IDC at diagnosis are maintained at each time point on treatment. Cancer Res; 74(19); 5371–6. ©2014 AACR.

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