scholarly journals Major Impact of Sampling Methodology on Gene Expression in Estrogen Receptor–Positive Breast Cancer

2018 ◽  
Vol 2 (2) ◽  
Author(s):  
Qiong Gao ◽  
Elena López-Knowles ◽  
Maggie Chon U Cheang ◽  
James Morden ◽  
Ricardo Ribas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Estrogen Receptor ◽  
Global Gene Expression ◽  
Control Group ◽  
Sampling Methodology ◽  
Estrogen Receptor Positive ◽  
The Impact ◽  
To Receive ◽  
Positive Breast Cancer

Abstract To investigate the impact of sampling methodology on gene expression data from primary estrogen receptor–positive (ER+) breast cancer biopsies, global gene expression was measured in core-cut biopsies at baseline and surgery from patients randomly assigned to receive either two weeks of presurgical aromatase inhibitor (AI; n = 157) or no presurgical treatment (n = 56). Those genes most markedly altered in the AI group (eg, FOS, DUSP1, RGS1, FOSB) were similarly altered in the no treatment group; some widely investigated genes that were apparently unaffected in the AI group (eg, MYC) were counter-altered in the control group, masking actual AI-dependent changes. In the absence of a control group, these artefactual changes would likely lead to the most affected genes being the erroneous focus of research. The findings are likely relevant to all archival collections of ER+ breast cancer.

scholarly journals Impact of aromatase inhibitor treatment on global gene expression and its association with antiproliferative response in ER+ breast cancer in postmenopausal patients

2019 ◽  
Vol 22 (1) ◽  
Author(s):  
Qiong Gao ◽  
◽  
Elena López-Knowles ◽  
Maggie Chon U. Cheang ◽  
James Morden ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cell Proliferation ◽  
Aromatase Inhibitor ◽  
Breast Cancer Mortality ◽  
Global Gene Expression ◽  
Therapy Resistance ◽  
Control Group ◽  
Short Term Exposure ◽  
The Impact

Abstract Background Endocrine therapy reduces breast cancer mortality by 40%, but resistance remains a major clinical problem. In this study, we sought to investigate the impact of aromatase inhibitor (AI) therapy on gene expression and identify gene modules representing key biological pathways that relate to early AI therapy resistance. Methods Global gene expression was measured on pairs of core-cut biopsies taken at baseline and at surgery from 254 patients with ER-positive primary breast cancer randomised to receive 2-week presurgical AI (n = 198) or no presurgical treatment (control n = 56) from the POETIC trial. Data from the AI group was adjusted to eliminate artefactual process-related changes identified in the control group. The response was assessed by changes in the proliferation marker, Ki67. Results High baseline ESR1 expression associated with better AI response in HER2+ tumours but not HER2− tumours. In HER2− tumours, baseline expression of 48 genes associated with poor antiproliferative response (p < 0.005) including PERP and YWHAQ, the two most significant, and the transcription co-regulators (SAP130, HDAC4, and NCOA7) which were among the top 16 most significant. Baseline gene signature scores measuring cell proliferation, growth factor signalling (ERBB2-GS, RET/GDNF-GS, and IGF-1-GS), and immune activity (STAT1-GS) were significantly higher in poor AI responders. Two weeks of AI caused downregulation of genes involved in cell proliferation and ER signalling, as expected. Signature scores of E2F activation and TP53 dysfunction after 2-week AI were associated with poor AI response in both HER2− and HER2+ patients. Conclusions There is a high degree of heterogeneity in adaptive mechanisms after as little as 2-week AI therapy; however, all appear to converge on cell cycle regulation. Our data support the evaluation of whether an E2F signatures after short-term exposure to AI may identify those patients most likely to benefit from the early addition of CDK4/6 inhibitors. Trial registration ISRCTN, ISRCTN63882543, registered on 18 December 2007.

Incidence and Predictive Factors for Recovery of Ovarian Function in Amenorrheic Women in Their 40s Treated With Letrozole

2016 ◽  
Vol 34 (14) ◽  
pp. 1594-1600 ◽  
Author(s):  
Lea K. Krekow ◽  
Beth A. Hellerstedt ◽  
Rufus P. Collea ◽  
Steven Papish ◽  
Shrinivas M. Diggikar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Ovarian Function ◽  
Follicle Stimulating Hormone ◽  
General Linear Model ◽  
Serum Estradiol ◽  
Function Recovery ◽  
Estrogen Receptor Positive ◽  
The Impact ◽  
Positive Breast Cancer

Purpose This prospective study assessed the impact of 2 years of aromatase inhibitor (AI) therapy on the incidence of ovarian function recovery (OFR) in women age 40 to 49 with estrogen receptor–positive breast cancer who were premenopausal at diagnosis and who underwent chemotherapy-induced amenorrhea during adjuvant treatment. Patients and Methods Women age 40 to 49 with estrogen receptor–positive breast cancer who had ceased menstruating with adjuvant cyclophosphamide-based chemotherapy, had postmenopausal serum estradiol (E2), and had received tamoxifen for ≥ 1 year were treated with letrozole (2.5 mg) daily for ≥ 2 years. Serum follicle-stimulating hormone (FSH) and E2 were measured at baseline and over 2 years. A general linear model was used to assess serial FSH by OFR. Logistic regression was used to assess baseline predictors and OFR. Results The study enrolled 177 women (145 women age 45 to 49 years and 32 women age 40 to 44 years). Of 173 evaluable patients, 67 (39%; 95% CI, 31% to 46%) regained ovarian function; 11 of these patients (6%; 95% CI, 3% to 10%) resumed menses, and 56 of these patients (32%; 95% CI, 25% to 39%) developed premenopausal E2 without menses. Among AI-naïve patients, serial FSH significantly increased over time (P < .001), did not vary significantly by OFR status (P = .55), but showed mild evidence of a decrease after month 12 for those who resumed menses (P = .0989). Age less than 45 years and inhibin B were significant multivariable baseline predictors of OFR. Conclusion These results emphasize the challenge in determining definitive menopause in women with chemotherapy-induced amenorrhea. The risk of OFR during treatment with AIs in amenorrheic women in their 40s is high, and AI therapy should be avoided in these patients.

scholarly journals Obesity-Altered Adipose Stem Cells Promote Radiation Resistance of Estrogen Receptor Positive Breast Cancer through Paracrine Signaling

2020 ◽  
Vol 21 (8) ◽  
pp. 2722 ◽  
Author(s):  
Rachel A. Sabol ◽  
Vidal A. Villela ◽  
Alexandra Denys ◽  
Benjamin T. Freeman ◽  
Alifiani B. Hartono ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Estrogen Receptor ◽  
Notch Signaling ◽  
Radiation Resistance ◽  
Adipose Stem Cells ◽  
Stromal Component ◽  
Estrogen Receptor Positive ◽  
The Impact ◽  
Positive Breast Cancer

Obesity is associated with poorer responses to chemo- and radiation therapy for breast cancer, which leads to higher mortality rates for obese women who develop breast cancer. Adipose stem cells (ASCs) are an integral stromal component of the tumor microenvironment (TME). In this study, the effects of obesity-altered ASCs (obASCs) on estrogen receptor positive breast cancer cell’s (ER+BCCs) response to radiotherapy (RT) were evaluated. We determined that BCCs had a decreased apoptotic index and increased surviving fraction following RT when co-cultured with obASCs compared to lnASCs or non-co-cultured cells. Further, obASCs reduced oxidative stress and induced IL-6 expression in co-cultured BCCs after radiation. obASCs produce increased levels of leptin relative to ASCs from normal-weight individuals (lnASCs). obASCs upregulate the expression of IL-6 compared to non-co-cultured BCCs, but BCCs co-cultured with leptin knockdown obASCs did not upregulate IL-6. The impact of shLeptin obASCs on radiation resistance of ER+BCCs demonstrate a decreased radioprotective ability compared to shControl obASCs. Key NOTCH signaling players were enhanced in ER+BBCs following co-culture with shCtrl obASCs but not shLep obASCs. This work demonstrates that obesity-altered ASCs, via enhanced secretion of leptin, promote IL-6 and NOTCH signaling pathways in ER+BCCs leading to radiation resistance.

Low–Estrogen Receptor–Positive Breast Cancer: The Impact of Tissue Sampling, Choice of Antibody, and Molecular Subtyping

2012 ◽  
Vol 30 (23) ◽  
pp. 2929-2930 ◽  
Author(s):  
Emad A. Rakha ◽  
Andrew H.S. Lee ◽  
Joseph Roberts ◽  
Nadia M. Villena Salinas ◽  
Zsolt Hodi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Tissue Sampling ◽  
Molecular Subtyping ◽  
Estrogen Receptor Positive ◽  
The Impact ◽  
Positive Breast Cancer
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