The critical role of surgical pathology in personalized medicine: The impact of biopsy cavities in breast cancer samples on recurrence risk when assessed by quantitative RT-PCR

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22016-e22016
Author(s):  
F. L. Baehner ◽  
J. Anderson ◽  
C. Millward ◽  
C. Sangli ◽  
C. Quale ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Expression Profiles ◽  
Critical Role ◽  
Recurrence Score ◽  
Pcr Analysis ◽  
Breast Cancers ◽  
Rt Pcr ◽  
Poorly Differentiated ◽  
The Impact

e22016 Background: Tumor gene expression analysis using the Recurrence Score (RS) assay is frequently used in ER+ breast cancer. Manual microdissection is performed in cases where biopsy cavities (BxC) are present in the submitted specimen. The objective of this was to characterize by quantitative RT-PCR the impact of BxC on 21 gene expression profiles and the RS. Methods: 48 (15 well, 18 moderate, and 15 poorly differentiated) breast cancers were evaluated for gene expression differences between whole sections (WS; containing BxC) and enriched tumor (ET; BxC excluded). Standardized quantitative RT-PCR analysis for the 21 Oncotype DX genes was performed; reference normalized gene expression measurements ranged from 0 to 15, where each 1-unit reflects an approximate 2-fold change in RNA. Analyses of individual genes and the RS were performed on the entire sample set and stratified by tumor grade. Correlation analyses used Pearson's R, concordance analysis used Lin's sample concordance and paired t- tests to characterize differences. Results: There were statistically significant differences in reference normalized gene expression between ET and WS in 6 genes: BAG1 (ET-WS: 0.13 units, p=0.0025), CD68 (ET-WS: -0.64 units, p<0.0001), ER (ET-WS: 0.29 units, p=0.0012), GSTM1 (ET-WS: 0.18 units p=0.0025), STK15 (ET-WS: -0.18 units, p=0.0041) and STMY3 (ET-WS: 0.62 units, p<0.0001). Expression of the macrophage marker CD68 was higher and expression of ER was lower in WS containing BxC. The correlation (0.95) and concordance (0.92) were generally high between WS and ET for RS overall however among moderately differentially tumors, there was a statistically significant mean increase in RS for WS of 3.3 units (p = 0.0012) while among poorly differentiated tumors there was a trend toward a statistically significant decrease in RS for WS of 2.2 units (p=0.0569). Conclusions: Histologic identification of invasive carcinoma and exclusion of BxC is essential for precise RS assessment. Inclusion of BxC in breast cancer specimens is associated with significant changes in the expression of individual genes and impacts the RS. Removal of BxC from breast cancer specimens assessed for gene expression levels is warranted. [Table: see text]

Gene expression profiles in formalin-fixed, paraffin-embedded (FFPE) core biopsies predict docetaxel chemosensitivity

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 538-538
Author(s):  
J. C. Chang ◽  
A. Makris ◽  
S. G. Hilsenbeck ◽  
J. R. Hackett ◽  
J. Jeong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Expression Profiles ◽  
Single Agent ◽  
Gene Expression Pattern ◽  
Predictive Test ◽  
Breast Cancers ◽  
Rt Pcr ◽  
Gene Group ◽  
Response To Chemotherapy

538 Background: Docetaxel has one of the highest response rates as a single agent in breast cancer, but de novo resistance is frequent. Previously, we had identified a 92-gene expression pattern that predicted response to neoadjuvant docetaxel. Other studies have validated that a high Recurrence Score (RS) by the 21-gene RT-PCR assay is predictive of worse prognosis (Paik, NEJM 2004) but better response to chemotherapy (Gianni, JCO 2005). We investigated whether tumor gene expression of these 21 genes and other candidate genes can predict response to docetaxel. Methods: Core biopsies from 97 patients were obtained before treatment with neoadjuvant docetaxel (4 cycles, 100 mg/m2 q3 weeks). Baseline and post-treatment measurements of the primary breast cancers were recorded. Three 10-micron FFPE sections were submitted for quantitative RT-PCR assays of 192 genes that were selected from our previous work and the literature. Results: Of the 97 patients, 81 (84%) had sufficient invasive breast cancer, 80 (82%) had sufficient RNA for assay of 192 genes, and 72 (74%) had clinical response data. Mean age was 48.5 years, and the median tumor size was 6 cm. Clinical complete responses (CR) by RECIST were observed in 12 (17%), partial responses in 41 (57%), stable disease in 17 (24%), and progressive disease in 2 patients (3%). The concordance of IHC and RT-PCR results was >80% for ER, PgR, and HER2. By univariate logistic regression, a significant correlation (p<0.05) between gene expression and CR was observed for 14 genes. Notably, CYBA-1 involved in mitochondrial metabolism, identified by gene expression profiling, significantly predicted CR (p=0.006). CR was associated with lower expression of the ER gene group and higher expression of the proliferation gene group. Multivariate analysis indicated that panels of genes better predictors of docetaxel response. Of note, CR was more likely with high RS and less likely with a low RS (p=0.008). Conclusion: We have established molecular profiles for breast cancers either responding or not responding to neoadjuvant docetaxel. This technology is a potential predictive test for docetaxel sensitivity by using small amounts of FFPE material, and may reduce unnecessary treatment, toxicity, and cost for breast cancer patients. [Table: see text]

scholarly journals Ovarian cycle stage critically affects 21-gene recurrence scores in Mmtv-Pymt mouse mammary tumours

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sarah M. Bernhardt ◽  
Pallave Dasari ◽  
Danielle J. Glynn ◽  
Lucy Woolford ◽  
Lachlan M. Moldenhauer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Menstrual Cycle ◽  
Recurrence Score ◽  
Gene Signature ◽  
Ovarian Cycle ◽  
Oncotype Dx ◽  
Mammary Tumours ◽  
Er Positive ◽  
The Impact

Abstract Background The Oncotype DX 21-gene Recurrence Score is predictive of adjuvant chemotherapy benefit for women with early-stage, estrogen receptor (ER)-positive, HER2-negative breast cancer. In premenopausal women, fluctuations in estrogen and progesterone during the menstrual cycle impact gene expression in hormone-responsive cancers. However, the extent to which menstrual cycling affects the Oncotype DX 21-gene signature remains unclear. Here, we investigate the impact of ovarian cycle stage on the 21-gene signature using a naturally cycling mouse model of breast cancer. Methods ER-positive mammary tumours were dissected from naturally cycling Mmtv-Pymt mice at either the estrus or diestrus phase of the ovarian cycle. The Oncotype DX 21-gene signature was assessed through quantitative real time-PCR, and a 21-gene experimental recurrence score analogous to the Oncotype DX Recurrence Score was calculated. Results Tumours collected at diestrus exhibited significant differences in expression of 6 Oncotype DX signature genes (Ki67, Ccnb1, Esr1, Erbb2, Grb7, Bag1; p ≤ 0.05) and a significant increase in 21-gene recurrence score (21.8 ± 2.4; mean ± SEM) compared to tumours dissected at estrus (15.5 ± 1.9; p = 0.03). Clustering analysis revealed a subgroup of tumours collected at diestrus characterised by increased expression of proliferation- (p < 0.001) and invasion-group (p = 0.01) genes, and increased 21-gene recurrence score (p = 0.01). No correlation between ER, PR, HER2, and KI67 protein abundance measured by Western blot and abundance of mRNA for the corresponding gene was observed, suggesting that gene expression is more susceptible to hormone-induced fluctuation compared to protein expression. Conclusions Ovarian cycle stage at the time of tissue collection critically affects the 21-gene signature in Mmtv-Pymt murine mammary tumours. Further studies are required to determine whether Oncotype DX Recurrence Scores in women are similarly affected by menstrual cycle stage.

scholarly journals Endurance Training Regulates Expression of Some Angiogenesis-Related Genes in Cardiac Tissue of Experimentally Induced Diabetic Rats

Biomolecules ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 498
Author(s):  
Mojdeh Khajehlandi ◽  
Lotfali Bolboli ◽  
Marefat Siahkuhian ◽  
Mohammad Rami ◽  
Mohammadreza Tabandeh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endurance Training ◽  
Molecular Mechanisms ◽  
Cardiac Tissue ◽  
Critical Role ◽  
Diabetic Rats ◽  
Moderate Intensity ◽  
Pcr Analysis ◽  
Cardiac Tissues ◽  
The Impact

Exercise can ameliorate cardiovascular dysfunctions in the diabetes condition, but its precise molecular mechanisms have not been entirely understood. The aim of the present study was to determine the impact of endurance training on expression of angiogenesis-related genes in cardiac tissue of diabetic rats. Thirty adults male Wistar rats were randomly divided into three groups (N = 10) including diabetic training (DT), sedentary diabetes (SD), and sedentary healthy (SH), in which diabetes was induced by a single dose of streptozotocin (50 mg/kg). Endurance training (ET) with moderate-intensity was performed on a motorized treadmill for six weeks. Training duration and treadmill speed were increased during five weeks, but they were kept constant at the final week, and slope was zero at all stages. Real-time polymerase chain reaction (RT-PCR) analysis was used to measure the expression of myocyte enhancer factor-2C (MEF2C), histone deacetylase-4 (HDAC4) and Calmodulin-dependent protein kinase II (CaMKII) in cardiac tissues of the rats. Our results demonstrated that six weeks of ET increased gene expression of MEF2C significantly (p < 0.05), and caused a significant reduction in HDAC4 and CaMKII gene expression in the DT rats compared to the SD rats (p < 0.05). We concluded that moderate-intensity ET could play a critical role in ameliorating cardiovascular dysfunction in a diabetes condition by regulating the expression of some angiogenesis-related genes in cardiac tissues.

Molecular characterization of male breast cancer by standardized quantitative RT-PCR analysis: First large genomic study of 347 male breast cancers compared to 82,434 female breast cancers

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 549-549 ◽  
Author(s):  
S. Shak ◽  
G. Palmer ◽  
F. L. Baehner ◽  
C. Millward ◽  
D. Watson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Male Breast Cancer ◽  
Recurrence Score ◽  
Cyclin B1 ◽  
Oncotype Dx ◽  
Male Breast ◽  
Breast Cancers ◽  
Genomic Study ◽  
Males And Females

549 Background: Because male breast cancer (BC) is rare, there is little known about the disease and treatment is extrapolated from female BC. Newer molecular technologies have not been used to profile male BC. We report here a study of quantitative gene expression by gender status in tumor specimens submitted for Recurrence Score testing. Methods: All estrogen receptor positive tumor specimens successfully examined in the Genomic Health laboratory from June 2004 through December 2008 were included. Quantitative expression for each gene was measured by the 21 gene oncotype DX assay on a scale from 0 to 15 (relative to reference genes), where a one unit increment is associated with a 2-fold change in expression. Results: There were 347 male and 82,434 female BCs. The males were older (mean age 63.8 vs 57.4 yrs). Standard histopathology was similar, although slightly more male BCs were ductal (83% vs 78%). Like female BC, there was a wide variation in gene expression in male BC. The distribution of RS in males and females was similar - RS mean (±SD) 18.1 (±11.2) in males and 19.1 (±10.2) in females (p = NS). The proportion of tumors with RS <18, 18 - 30, and ≥ 31 was 53.6%, 35.2%, and 11.2% in males and 53.4%, 36.3%, and 10.3% in females. Although the patterns of expression of the Oncotype DX genes were more similar than different in males and females some differences were notable. Mean expression of ER, PR, and SCUBE2 were 0.5 units higher in males. Mean expression of the proliferation genes, Ki-67, MYBL2, Survivin, Cyclin B1, and STK15, were 0.5 units higher in males. Mean expression of STMY3 was 0.9 units higher in males. Of note, whereas the level of quantitative ER significantly increased with increasing patient age in females (0.4 units per decade), little increase was observed in males (<0.1 units per decade). Conclusions: This large genomic study of male BC reveals a heterogeneous biology as measured by the standardized quantitative oncotype DX breast cancer assay, similar to that observed in female BC. Some differences, which may reflect the differences in hormone biology between males and females, were noted and deserve further study. [Table: see text]

Age-related changes in the transcriptional profile of mouse RPE/choroid

2003 ◽  
Vol 15 (3) ◽  
pp. 258-262 ◽  
Author(s):  
Hisashi Ida ◽  
Sharon A. Boylan ◽  
Andrea L. Weigel ◽  
Leonard M. Hjelmeland
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Cdna Probe ◽  
Gene Expression Profiles ◽  
Age Related Macular Degeneration ◽  
Pcr Analysis ◽  
Rt Pcr ◽  
Mouse Cdna ◽  
Age Related ◽  
Age Related Changes

To evaluate the age-related changes in gene expression occurring in the complex of retinal pigmented epithelium, Bruch’s membrane, and choroid (RPE/choroid), we examined the gene expression profiles of young adult (2 mo) and old (24 mo) male C57BL/6 mice. cDNA probe sets from individual animals were synthesized using total RNA isolated from the RPE/choroid of each animal. Probes were amplified using the Clontech SMART system, radioactively labeled, and hybridized to two different Clontech Atlas mouse cDNA arrays. From each age group, three independent triplicates were hybridized to the arrays. Statistical analyses were performed using the Significance Analysis of Microarrays program (SAM version 1.13; Stanford University). Selected array results were confirmed by semi-quantitative RT-PCR analysis. Of 2,340 genes represented on the arrays, ∼60% were expressed in young and/or old mouse RPE/choroid. A moderate fraction (12%) of all expressed genes exhibited a statistically significant change in expression with age. Of these 150 genes, all but two, HMG14 and carboxypeptidase E, were upregulated with age. Many of these upregulated genes can be grouped into several broad functional categories: immune response, proteases and protease inhibitors, stress response, and neovascularization. RT-PCR results from six of six genes examined confirmed the differential change in expression with age of these genes. Our study provides likely candidate genes to further study their role in the development of age-related macular degeneration and other aging diseases affecting the RPE/choroid.

scholarly journals A novel immune subtype classification of ER-positive, PR-negative and HER2-negative breast cancer based on the genomic and transcriptomic landscape

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Peiling Xie ◽  
Rui An ◽  
Shibo Yu ◽  
Jianjun He ◽  
Huimin Zhang
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Clinical Outcomes ◽  
Immune Escape ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Molecular Characteristics ◽  
Consensus Clustering ◽  
Breast Cancers ◽  
Her2 Breast Cancer

Abstract Background The diversity and plasticity behind ER+/PR−/HER2− breast cancer have not been widely explored. It is essential to identify heterogeneous microenvironment phenotypes and investigate specific genomic events driving the formation of these phenotypes. Methods Based on the immune-related gene expression profiles of 411 ER+/PR−/HER2− breast cancers in the METABRIC cohort, we used consensus clustering to identify heterogeneous immune subtypes and assessed their reproducibility in an independent meta-cohort including 135 patients collected from GEO database. We further analyzed the differences of cellular and molecular characteristics, and potential immune escape mechanism among immune subtypes. In addition, we constructed a transcriptional trajectory to visualize the distribution of individual patient. Results Our analysis identified and validated five reproducible immune subtypes with distinct cellular and molecular characteristics, potential immune escape mechanisms, genomic drivers, as well as clinical outcomes. An immune-cold subtype, with the least amount of lymphocyte infiltration, had a poorer prognosis. By contrast, an immune-hot subtype, which demonstrated the highest infiltration of CD8+ T cells, DCs and NK cells, and elevated IFN-γ response, had a comparatively favorable prognosis. Other subtypes showed more diverse gene expression and immune infiltration patterns with distinct clinical outcomes. Finally, our analysis revealed a complex immune landscape consisting of both discrete cluster and continuous spectrum. Conclusion Overall, this study revealed five heterogeneous immune subtypes among ER+/PR–/HER2− breast cancer, also provided important implications for clinical translations.

scholarly journals The Gonococcal Fur-Regulated tbpA and tbpB Genes Are Expressed during Natural Mucosal Gonococcal Infection

2005 ◽  
Vol 73 (7) ◽  
pp. 4281-4287 ◽  
Author(s):  
Sarika Agarwal ◽  
Carol A. King ◽  
Ellen K. Klein ◽  
David E. Soper ◽  
Peter A. Rice ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Iron Concentration ◽  
Pcr Analysis ◽  
Positive Trend ◽  
Gonococcal Infection ◽  
Rt Pcr ◽  
Male Subjects

ABSTRACT Iron is limiting in the human host, and bacterial pathogens respond to this environment by regulating gene expression through the ferric uptake regulator protein (Fur). In vitro studies have demonstrated that Neisseria gonorrhoeae controls the expression of several critical genes through an iron- and Fur-mediated mechanism. While most in vitro experiments are designed to determine the response of N. gonorrhoeae to an exogenous iron concentration of zero, these organisms are unlikely to be exposed to such severe limitations of iron in vivo. To determine if N. gonorrhoeae expresses iron- and Fur-regulated genes in vivo during uncomplicated gonococcal infection, we examined gene expression profiles of specimens obtained from male subjects with urethral infections. RNA was isolated from urethral swab specimens and used as a template to amplify, by reverse transcriptase PCR (RT-PCR), gonococcal genes known to be regulated by iron and Fur (tbpA, tbpB, and fur). The constitutively expressed gonococcal rmp gene was used as a positive control. RT-PCR analysis indicated that gonorrhea-positive specimens where rmp expression was seen were also 93% (51/55) fbpA positive, 87% (48/55) tbpA positive, and 86% (14 of 16 tested) tbpB positive. In addition, we detected a fur transcript in 79% (37 of 47 tested) of positive specimens. We also measured increases in levels of immunoglobulin G antibody against TbpA (91%) and TbpB (73%) antigens in sera from infected male subjects compared to those in uninfected controls. A positive trend between tbpA gene expression and TbpA antibody levels in sera indicated a relationship between levels of gene expression and immune response in male subjects infected with gonorrhea for the first time. These results indicate that gonococcal iron- and Fur-regulated tbpA and tbpB genes are expressed in gonococcal infection and that male subjects with mucosal gonococcal infections exhibit antibodies to these proteins.

scholarly journals Prognostic Genes of Breast Cancer Identified by Gene Co-expression Network Analysis

2020 ◽  
Author(s):  
Jianing Tang ◽  
Yongwen Luo ◽  
Gaosong Wu
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cell Proliferation ◽  
Network Analysis ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Gene Expression Omnibus ◽  
Validation Dataset ◽  
Pcr Analysis ◽  
Normal Tissues

Abstract Background Breast cancer is the mostly diagnosed malignance in female worldwide. However, the mechanisms of its pathogenesis remain largely unknown. Methods In this study, we used weighted gene co-expression network analysis (WGCNA) to identify novel biomarkers associated with the prognosis of breast cancer. Gene expression profiles were obtained from the Gene Expression Omnibus (GEO) database. Results A total of 5 modules were identified via the average linkage hierarchical clustering. And a module significantly with the pathological grade was screened out. 33 genes with high connectivity in the clinically significant module were identified as hub genes. Among them, CASC5 and RAD51 were negatively associated with the overall survival and disease-specific survival. Similar results were observed in the validation dataset. Protein levels of CACS5 and RAD51 were also significantly higher in tumor tissues compared with normal tissues based on the analysis of the Human Protein Atlas. Convincingly, qRT-PCR analysis of breast cancer tissues and matched paracancerous tissue demonstrated that CACS5 and RAD51 were significantly upregulated in in breast cancer compared to paracancerous tissues. Further cell proliferation assay indicated that CACS5 and RAD51 depletion decreased cell proliferation capability. Conclusion In conclusion, our findings suggested that CASC5 and RAD51 could serve as biomarkers related to the prognosis of breast cancer and may be helpful for revealing pathogenic mechanism and developing further research.

Gene expression profiling can predict pathological complete response (pCR) to anthracycline-based therapy in estrogen- receptor (ER) negative breast cancer (BC) patients

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10564-10564
Author(s):  
C. Desmedt ◽  
F. André ◽  
E. Azambuja ◽  
B. Haibe-Kains ◽  
D. Larsimont ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Expression Profiles ◽  
Single Agent ◽  
Gene Expression Profiles ◽  
Molecular Transport ◽  
Complete Response ◽  
Dominant Factor ◽  
Breast Cancers ◽  
Two Samples

10564 Background: Breast cancers show variable sensitivity to anthracycline (A)-based therapy. Here we aimed to identify gene expression profiles associated with pCR to this treatment. As it has repeatedly and consistently been shown that ER is the most dominant factor influencing the molecular composition of breast cancer, defining different types of BC disease and because we wanted to eliminate the confounding effect of indirect ovarian suppression in ER+ BC, we focused in this study on ER-negative patients only. Methods: We analyzed Affymetrix gene expression profiles generated from 132 ER- pre-treatment samples, constituting the largest series of ER- preoperatively A-treated BC (n=132/35 pCR). Sixty-two samples derived from the prospective multicentric TOP trial (epirubicin single-agent), 41 from Institut G. Roussy (retrospective selection/ FEC) and 27 from MD Anderson (prospective study/ FAC). Results: A student t- test analysis on the combined population of A-treated pts was performed identifying 102 genes that were significantly associated with pCR (p<.01). These genes were mainly involved in cell death, DNA replication and recombination, molecular transport, cell cycle and morphology. Interestingly, 14 of these genes were located on the topoIIa amplicon. Of interest, none of these 14 genes seem to carry any prognostic value in untreated ER- pts (N=161). When we considered gene expression indices for specific A-targets such as topoIIa and helicase, we found that both were associated with pCR. However, subgroup analysis revealed that topoIIa index was predictive in ERBB2+ but not in ERBB2- subgroup. None of the genes from the adriamycin predictor (Potti et al.) or the p53 signature (Miller et al.) were significantly associated with pCR. Conclusions: This study suggests that a group of genes associated with topoIIa can identify ER-negative BC pts likely to respond to A-based therapy. These promising results are currently being validated in a larger series. No significant financial relationships to disclose.

Evaluation of the Oncotype Dx recurrence score (RS) in hormone-positive ipsilateral breast tumor recurrences.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11032-e11032
Author(s):  
Irene Wapnir ◽  
Marilyn Florero
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Breast Tumor ◽  
Expression Profiles ◽  
Pearson Correlation ◽  
Recurrence Score ◽  
Oncotype Dx ◽  
Time Interval ◽  
Ipsilateral Breast ◽  
Study Results

e11032 Background: IBTR (ipsilateral breast tumor recurrence) is considered a marker of risk for metastasis. Most IBTRs occur in the vicinity of the index tumor while elsewhere recurrences may represent new primaries. Oncotype DX®, 21-gene expression assay, quantifies a recurrence score (RS) in node negative, ER+ breast cancer. This modality can guide treatment decisions and has been extended to select node positive patients. Concordance of RS between the primary and IBTR is presented here. Methods: Archival blocks corresponding of 11 patients were obtained but only 8 were evaluable. The blocks were submitted using a blinded identification scheme to link the primary and recurrent tumor blocks. All were ER positive breast cancers. Six were N0, one N1, and one NX. Some assay results were preexisting. RS and single gene expression profiles for ER, PR and HER2 were compared. Scatterplots and descriptive statistics were produced for this exploratory hypothesis-generating (but not hypothesis-testing) study. Results: The time interval between primary and recurrence ranged from 12 to 216 months (mean 73.5 months). Among the 8 paired samples, RS’s were similar in 5 and different in 3. In the latter, RS shifted from 2 to 29, 15 to 23 and 25 to 14. These IBTRs occurred in a different quadrant, were simultaneous with axillary recurrence, or appeared after trastuzumab therapy. Overall, the Pearson correlation coefficient was 0.68 (95% CI -0.09, 0.93). Only one case shifted from ER+ to ER-; two cases from PR+ to PR- and one from PR- to PR+. No change in HER2 status was noted. The paired differences for ER were -0.01 (95% CI -1.09, 1.07), PR -0.74 ( 95% CI -2.43, 0.96) and HER2 -0.51 (95% CI -1.20, 0.17). The Pearson correlation coefficients and 95% CI were ER 0.72 (-0.02, 0.94); PR 0.61 (-0.22, 0.91); and HER2 0.89 (0.45, 0.98) respectively. Conclusions: The RS of the IBTR was similar to primary breast cancer in 5 of 8 cases in this exploratory pilot study. Hormone receptor status changed in only one of 8 cases. The clinical significance of these observations and the utility of these results in guiding therapeutic strategies is unknown.

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