scholarly journals High CYP27A1 expression is a biomarker of favorable prognosis in premenopausal patients with estrogen receptor positive primary breast cancer

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Maria Inasu ◽  
Pär-Ola Bendahl ◽  
Mårten Fernö ◽  
Per Malmström ◽  
Signe Borgquist ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Distant Recurrence ◽  
Cancer Treatments ◽  
Free Survival ◽  
Node Negative ◽  
Estrogen Receptor Positive ◽  
Premenopausal Patients ◽  
Multivariable Analyses

Abstract27-hydroxycholesterol (27HC), synthesized from cholesterol by the enzyme CYP27A1, differentially impacts estrogen receptor positive (ER+) breast cancer (BC) cell growth depending on estrogen levels. This study examined the association between CYP27A1 expression and prognosis in a cohort of 193 premenopausal patients with lymph node-negative primary BC with limited exposure to adjuvant systemic cancer treatments. In multivariable analyses among patients with ER+ tumors, high CYP27A1 protein and mRNA expressions were associated with four- and eight-fold reductions in the incidence of distant recurrence-free survival events: HRadj = 0.26, 95% CI = 0.07–0.93 and HRadj = 0.13, 95% CI = 0.03–0.60, respectively. In vitro studies revealed that 27HC treatment potently inhibited ER+ BC cell proliferation under lipid-depleted conditions regardless of estradiol levels, transcriptionally mediated through the downregulation of ER signaling with a concomitant upregulation of cholesterol export. Importantly, if validated, these results may have implications for adjuvant treatment decisions in premenopausal patients, especially when de-escalation of therapy is being considered.

Gene Expression and Benefit of Chemotherapy in Women With Node-Negative, Estrogen Receptor–Positive Breast Cancer

2006 ◽  
Vol 24 (23) ◽  
pp. 3726-3734 ◽  
Author(s):  
Soonmyung Paik ◽  
Gong Tang ◽  
Steven Shak ◽  
Chungyeul Kim ◽  
Joffre Baker ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Relative Risk ◽  
Distant Recurrence ◽  
Chemotherapy Treatment ◽  
Node Negative ◽  
Estrogen Receptor Positive ◽  
Large Benefit ◽  
Absolute Decrease ◽  
Positive Breast Cancer

Purpose The 21-gene recurrence score (RS) assay quantifies the likelihood of distant recurrence in women with estrogen receptor–positive, lymph node–negative breast cancer treated with adjuvant tamoxifen. The relationship between the RS and chemotherapy benefit is not known. Methods The RS was measured in tumors from the tamoxifen-treated and tamoxifen plus chemotherapy–treated patients in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B20 trial. Cox proportional hazards models were utilized to test for interaction between chemotherapy treatment and the RS. Results A total of 651 patients were assessable (227 randomly assigned to tamoxifen and 424 randomly assigned to tamoxifen plus chemotherapy). The test for interaction between chemotherapy treatment and RS was statistically significant (P = .038). Patients with high-RS (≥ 31) tumors (ie, high risk of recurrence) had a large benefit from chemotherapy (relative risk, 0.26; 95% CI, 0.13 to 0.53; absolute decrease in 10-year distant recurrence rate: mean, 27.6%; SE, 8.0%). Patients with low-RS (< 18) tumors derived minimal, if any, benefit from chemotherapy treatment (relative risk, 1.31; 95% CI, 0.46 to 3.78; absolute decrease in distant recurrence rate at 10 years: mean, −1.1%; SE, 2.2%). Patients with intermediate-RS tumors did not appear to have a large benefit, but the uncertainty in the estimate can not exclude a clinically important benefit. Conclusion The RS assay not only quantifies the likelihood of breast cancer recurrence in women with node-negative, estrogen receptor–positive breast cancer, but also predicts the magnitude of chemotherapy benefit.

MDM2 amplification is an independent prognostic feature of node-negative, estrogen receptor-positive early-stage breast cancer

2011 ◽  
Vol 8 (2) ◽  
pp. 53-60 ◽  
Author(s):  
Matthias Choschzick ◽  
Uwe Heilenkötter ◽  
Annette Lebeau ◽  
Fritz Jaenicke ◽  
Luigi Terracciano ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Early Stage ◽  
Early Stage Breast Cancer ◽  
Node Negative ◽  
Estrogen Receptor Positive ◽  
Prognostic Feature ◽  
Mdm2 Amplification

scholarly journals Virtual screening of natural compounds as combinatorial agents from indian medicinal plants against estrogen positive breast cancer

2020 ◽  
Vol 3 (10) ◽  
pp. 266-275
Author(s):  
Shaleen Jain ◽  
Dr. Asmita Das
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Virtual Screening ◽  
Medicinal Plants ◽  
Natural Compounds ◽  
Binding Energies ◽  
Common Amino Acid ◽  
Estrogen Receptor Positive ◽  
Positive Breast Cancer

Facing worldwide challenges associated with multifactorial etiology of breast cancer, designing of combinatorial therapies using natural compounds is currently the emergent way of treating several cancers including breast cancer in a synergistic way, which may mitigate several problems associated with multiple receptor targeting. In this research, Estrogen receptor positive breast cancer was taken as prototype and several key receptors associated with this particular disease were targeted by virtual screening of natural compounds found in Indian originated medicinal plants using Computer aided Drug Designing (CADD) strategies. We found the combination of Carpusin, Paulownin Cornigerine, Nororientaline, Oryzalexin B, Romucosine H and Colchicine as effective against six potential receptors i.e. FGFR2, ESR1, PIK3CA, PIK3CB, PIK3CD and AR in Estrogen receptor positive breast cancer with their binding energies in the range of ∆G ≤ -8.0 Kcal/mol as well as significant number of common amino acid binding residues as compared with binding sites of receptors. Thus this research holds significant implications for the designing of combinatorial therapeutic agents against breast cancer which can be further tested in-vitro and in-vivo to prove their synergistic efficiency.

Multicenter Validation of a Gene Expression–Based Prognostic Signature in Lymph Node–Negative Primary Breast Cancer

2006 ◽  
Vol 24 (11) ◽  
pp. 1665-1671 ◽  
Author(s):  
John A. Foekens ◽  
David Atkins ◽  
Yi Zhang ◽  
Fred C.G.J. Sweep ◽  
Nadia Harbeck ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Distant Metastasis ◽  
Gene Signature ◽  
Breast Cancer Patients ◽  
Prognostic Signature ◽  
Free Survival ◽  
Node Negative ◽  
Distant Metastasis Free Survival ◽  
Multicenter Validation

Purpose We previously identified in a single-center study a 76-gene prognostic signature for lymph node-negative (LNN) breast cancer patients. The aim of this study was to validate this gene signature in an independent more diverse population of LNN patients from multiple institutions. Patients and Methods Using custom-designed DNA chips we analyzed the expression of the 76 genes in RNA of frozen tumor samples from 180 LNN patients who did not receive adjuvant systemic treatment. Results In this independent validation, the 76-gene signature was highly informative in identifying patients with distant metastasis within 5 years (hazard ratio, [HR], 7.41; 95% CI, 2.63 to 20.9), even when corrected for traditional prognostic factors in multivariate analysis (HR, 11.36; 95% CI, 2.67 to 48.4). The actuarial 5- and 10-year distant metastasis-free survival were 96% (95% CI, 89% to 99%) and 94% (95% CI, 83% to 98%), respectively, for the good profile group and 74% (95% CI, 64% to 81%) and 65% (53% to 74%), respectively for the poor profile group. The sensitivity for 5-yr distant metastasis-free survival was 90%, and the specificity was 50%. The positive and negative predictive values were 38% (95% CI, 29% to 47%) and 94% (95% CI, 86% to 97%), respectively. The 76-gene signature was confirmed as a strong prognostic factor in subgroups of estrogen receptor-positive patients, pre- and postmenopausal patients, and patients with tumor sizes 20 mm or smaller. The subgroup of patients with estrogen receptor-negative tumors was considered too small to perform a separate analysis. Conclusion Our data provide a strong methodologic and clinical multicenter validation of the predefined prognostic 76-gene signature in LNN breast cancer patients.

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