scholarly journals Retinoid X receptor gamma (RXRG) is an independent prognostic biomarker in ER-positive invasive breast cancer

2019 ◽  
Vol 121 (9) ◽  
pp. 776-785 ◽  
Author(s):  
Chitra Joseph ◽  
Sara Al-Izzi ◽  
Mansour Alsaleem ◽  
Sasagu Kurozumi ◽  
Michael S Toss ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Patient Outcome ◽  
Distant Metastasis ◽  
Prognostic Significance ◽  
Retinoid X Receptor ◽  
Cancer Tissue ◽  
Lower Grade ◽  
Breast Cancer Specific Survival ◽  
Cancer Specific Survival ◽  
Er Positive

Abstract Background Retinoid X Receptor Gamma (RXRG) is a member of the nuclear receptor superfamily and plays a role in tumour suppression. This study aims to explore the prognostic significance of RXRG in breast cancer. Methods Primary breast cancer tissue microarrays (n = 923) were immuno-stained for RXRG protein and correlated with clinicopathological features, and patient outcome. Results Nuclear RXRG expression was significantly associated with smaller tumour size (p = 0.036), lower grade (p < 0.001), lobular histology (p = 0.016), lower Nottingham Prognostic Index (p = 0.04) and longer breast cancer-specific survival (p < 0.001), and longer time to distant metastasis (p = 0.002). RXRG expression showed positive association with oestrogen receptor (ER)-related biomarkers: GATA3, FOXA1, STAT3 and MED7 (all p < 0.001) and a negative correlation with the Ki67 proliferation marker. Multivariate analysis demonstrated RXRG protein as an independent predictor of longer breast cancer-specific survival and distant metastasis-free survival. In the external validation cohorts, RXRG expression was associated with improved patients’ outcome (p = 0.025). In ER-positive tumours, high expression of RXRG was associated with better patient outcome regardless of adjuvant systemic therapy. ER signalling pathway was the top predicted master regulator of RXRG protein expression (p = 0.005). Conclusion This study provides evidence for the prognostic value of RXRG in breast cancer particularly the ER-positive tumours.

scholarly journals Lumpectomy Plus Tamoxifen With or Without Irradiation in Women Age 70 Years or Older With Early Breast Cancer: Long-Term Follow-Up of CALGB 9343

2013 ◽  
Vol 31 (19) ◽  
pp. 2382-2387 ◽  
Author(s):  
Kevin S. Hughes ◽  
Lauren A. Schnaper ◽  
Jennifer R. Bellon ◽  
Constance T. Cirrincione ◽  
Donald A. Berry ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Radiation Therapy ◽  
Distant Metastasis ◽  
Early Stage ◽  
Breast Cancer Specific Survival ◽  
Cancer Specific Survival ◽  
Er Positive ◽  
Long Term Follow Up

Purpose To determine whether there is a benefit to adjuvant radiation therapy after breast-conserving surgery and tamoxifen in women age ≥ 70 years with early-stage breast cancer. Patients and Methods Between July 1994 and February 1999, 636 women (age ≥ 70 years) who had clinical stage I (T1N0M0 according to TNM classification) estrogen receptor (ER) –positive breast carcinoma treated by lumpectomy were randomly assigned to receive tamoxifen plus radiation therapy (TamRT; 317 women) or tamoxifen alone (Tam; 319 women). Primary end points were time to local or regional recurrence, frequency of mastectomy, breast cancer–specific survival, time to distant metastasis, and overall survival (OS). Results Median follow-up for treated patients is now 12.6 years. At 10 years, 98% of patients receiving TamRT (95% CI, 96% to 99%) compared with 90% of those receiving Tam (95% CI, 85% to 93%) were free from local and regional recurrences. There were no significant differences in time to mastectomy, time to distant metastasis, breast cancer–specific survival, or OS between the two groups. Ten-year OS was 67% (95% CI, 62% to 72%) and 66% (95% CI, 61% to 71%) in the TamRT and Tam groups, respectively. Conclusion With long-term follow-up, the previously observed small improvement in locoregional recurrence with the addition of radiation therapy remains. However, this does not translate into an advantage in OS, distant disease-free survival, or breast preservation. Depending on the value placed on local recurrence, Tam remains a reasonable option for women age ≥ 70 years with ER-positive early-stage breast cancer.

Surgery versus primary endocrine therapy for elderly women with estrogen receptor-positive early operable primary breast cancer: Survival analysis and correlation with oestrogen receptor positivity

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 612-612
Author(s):  
B. M. Syed ◽  
S. J. Johnston ◽  
D. W. M. Wong ◽  
D. A. L. Morgan ◽  
I. O. Ellis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Primary Breast Cancer ◽  
Oestrogen Receptor ◽  
Elderly Women ◽  
Breast Cancer Specific Survival ◽  
Cancer Specific Survival ◽  
Er Positive ◽  
Primary Endocrine Therapy

612 Background: A recent Cochrane review of seven randomised trials involving 1,446 elderly women (unselected for oestrogen receptor (ER) status) has shown no significant difference in overall survival between surgery (with or without adjuvant tamoxifen) and primary endocrine therapy using tamoxifen. We now report results of a large series from a single centre with a dedicated elderly breast cancer service, with long term follow-up. Methods: During a period of > 20 years, 1,031 elderly (> 70 years) women with ER positive (H-score >50) early operable primary breast cancer received either surgery (with or without adjuvant endocrine therapy) (N = 436) or primary endocrine therapy (N = 595) (>80% using tamoxifen) as initial treatment, with complete follow-up information till deaths. The initial treatment was decided based on fitness for surgery and patient choice. Analysis was carried out on breast cancer specific survival and degree of ER positivity. Results: After a median follow up of 49 months (range 0 - 261 months), patients between 70 - 80 years, treated by surgery, had better 5-year breast cancer specific survival compared to their counterparts treated by primary endocrine therapy (95% versus 85%; p < 0.001). For patients > 80 years, there was however no statistical difference between the two groups (90% versus 90%; p = 0.813). The median survival has not reached yet in all groups. Patients in the latter group (> 80 years) were found to have a higher chance of having strongly ER positive tumours (57% versus 50% in patients between 70 - 80 years with H-score >200; p- < 0.02). Conclusions: In a selected group of elderly women (> 80 years) who tend to have strongly ER positive tumours, surgery and primary endocrine therapy did not appear to produce any difference in breast cancer specific survival. This subject is currently being investigated in a national randomised trial in the UK. No significant financial relationships to disclose.

Use of multiplex mutation genotyping to identify novel and protective mutations in breast cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 11004-11004
Author(s):  
K. Kalinsky ◽  
L. M. Jacks ◽  
C. Hedvat ◽  
U. Bhanot ◽  
S. Patil ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Pik3ca Mutation ◽  
Prognostic Significance ◽  
Predictive Biomarkers ◽  
Breast Tumors ◽  
Tumor Biomarker ◽  
Lower Grade ◽  
Cancer Specific Survival ◽  
Mutation Status ◽  
Pik3ca Mutations

11004 Background: We recently analyzed 590 primary invasive breast tumors for PIK3CA mutations by multiplex massARRAY genotyping. We identified a 32.5% PIK3CA mutation rate (manuscript submitted). Associations between PIK3CA mutation status and favorable pathology, such as lower grade tumors, lymph node negativity and hormone receptor (HR) positivity, were observed. Multiplex analysis allows the rapid assessment of mutations not commonly described in breast cancer. To identify activated pathways that may serve as predictive biomarkers, tissue microarrays (TMA) underwent immunohistochemical (IHC) analysis. Methods: 590 archival formalin-fixed paraffin embedded (FFPE) tumors > 1 cm were used to ensure adequate tissue procurement for mutation detection and TMA construction. MassARRAY (Sequenom) genotyping was performed on native DNA to identify PIK3CA, RAS, RET, and other known mutations. IHC staining of the TMAs included assessment of steroid nuclear receptors, HER2 expression, Akt pathway activation (including pAKT, p70S6K, eIF4E), and PTEN. Stained TMAs underwent digital quantitative image analysis and scoring (Aperio, Vista, CA). The Kaplan-Meier method and Cox models were used in univariate and multivariate analysis for associations of mutation status and clinicopathologic features on overall survival (OS) and breast cancer-specific survival (BCSS). Results: Compared to wild-type, PIK3CA mutated tumors (median f/u: 12.8 years) demonstrate a significant improvement in OS (p=0.03) and BCSS (p=0.004). For patients with any PIK3CA mutation, the improvement in BCSS is maintained in HR positive and ER negative subgroups. In addition to PIK3CA mutations, RAS and RET mutations are identified in a small proportion of breast tumors. Additional analysis to evaluate the association of mutation status and biomarker data derived from the TMA analysis will be performed for meeting presentation. Conclusions: We have recently defined the positive prognostic significance of PIK3CA mutations in breast cancer. RAS mutations are confirmed to occur rarely in breast cancer. The finding of RET mutations in breast cancer is novel. Future tumor biomarker identification directed towards predictive measurement will assist in tailoring therapy to appropriate patient populations. No significant financial relationships to disclose.

scholarly journals Prognostic significance of KN motif and ankyrin repeat domains 1 (KANK1) in invasive breast cancer

2019 ◽  
Vol 179 (2) ◽  
pp. 349-357 ◽  
Author(s):  
Yousif A. Kariri ◽  
Chitra Joseph ◽  
Sasagu Kurozumi ◽  
Michael S. Toss ◽  
Mansour Alsaleem ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Expression ◽  
Invasive Breast Cancer ◽  
Tumour Size ◽  
Molecular Taxonomy ◽  
Prognostic Significance ◽  
Ankyrin Repeat ◽  
The Cancer Genome Atlas ◽  
Lower Grade ◽  
Cancer Specific Survival

Abstract Background KN motif and ankyrin repeat domains 1 (KANK1) plays an important role in cytoskeleton maintenance and contributes to the regulation of cell proliferation, adhesion and apoptosis. KANK1 is involved in progression of a variety of solid tumours; however, its role in invasive breast cancer (BC) remains unknown. This study aims to evaluate the clinicopathological and prognostic value of KANK1 expression in operable BC. Methods KANK1 expression was assessed at the transcriptomic level using multiple BC cohorts; the Molecular Taxonomy of BC International Consortium cohort (METABRIC; n = 1980), The Cancer Genome Atlas BC cohort (TCGA; n = 949) and the publicly available BC transcriptomic data hosted by BC Gene-Expression Miner (bc-GenExMiner v4.0) and Kaplan–Meier plotter?. The Nottingham BC cohort (n = 1500) prepared as tissue microarrays was used to assess KANK1 protein expression using immunohistochemistry (IHC). The association between clinicopathological variables and patient outcome was investigated. Results In the METABRIC cohort, high expression of KANK1 mRNA was associated with characteristics of good prognosis including lower grade, absence of lymphovascular invasion and HER2 negativity (all; p < 0.001) and with better outcome [p = 0.006, Hazards ratio, (HR) 0.70, 95% CI 0.54–0.91]. High KANK1 protein expression was correlated with smaller tumour size and HER2 negativity, and better outcome in terms of longer breast cancer-specific survival [p = 0.013, HR 0.7, 95% CI 0.536–0.893] and time to distant metastasis [p = 0.033, HR 0.65, 95% CI 0.51–0.819]. Conclusion These results supported that upregulation of KANK1 works as a tumour suppressor gene in BC and is associated with improved patients’ outcomes.

scholarly journals The Biological and Clinical Significance of Glutaminase in Luminal Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 3963
Author(s):  
Brendah K. Masisi ◽  
Rokaya El Ansari ◽  
Lutfi Alfarsi ◽  
Madeleine L. Craze ◽  
Natasha Jewa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Patient Outcome ◽  
Ductal Carcinoma ◽  
Tumour Size ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Glutamine Metabolism ◽  
Gene Copy ◽  
Luminal Breast Cancer ◽  
Potential Biomarker

The glutamine metabolism has a key role in the regulation of uncontrolled tumour growth. This study aimed to evaluate the expression and prognostic significance of glutaminase in luminal breast cancer (BC). The glutaminase isoforms (GLS/GLS2) were assessed at genomic/transcriptomic levels, using METABRIC (n = 1398) and GeneMiner datasets (n = 4712), and protein using immunohistochemistry in well-characterised cohorts of Oestrogen receptor-positive/HER2-negative BC patients: ductal carcinoma in situ (DCIS; n = 206) and invasive breast cancer (IBC; n = 717). Glutaminase expression was associated with clinicopathological features, patient outcome and glutamine-metabolism-related genes. In DCIS, GLS alone and GLS+/GLS2- expression were risk factors for shorter local recurrence-free interval (p < 0.0001 and p = 0.001, respectively) and remained prognostic factors independent of tumour size, grade and comedo necrosis (p = 0.0008 and p = 0.003, respectively). In IBC, GLS gene copy number gain with high mRNA expression was associated with poor patient outcome (p = 0.011), whereas high GLS2 protein was predictive of a longer disease-free survival (p = 0.006). Glutaminase plays a role in the biological function of luminal BC, particularly GLS in the early non-invasive stage, which could be used as a potential biomarker to predict disease progression and a target for inhibition. Further validation is required to confirm these observations, and functional assessments are needed to explore their specific roles.

scholarly journals Trends in Survival Over the Past Two Decades Among White and Black Patients With Newly Diagnosed Stage IV Breast Cancer

2008 ◽  
Vol 26 (30) ◽  
pp. 4891-4898 ◽  
Author(s):  
Shaheenah Dawood ◽  
Kristine Broglio ◽  
Ana M. Gonzalez-Angulo ◽  
Aman U. Buzdar ◽  
Gabriel N. Hortobagyi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stage Iv ◽  
The United States ◽  
Breast Cancer Specific Survival ◽  
Newly Diagnosed ◽  
Cancer Specific Survival ◽  
Risk Of Death ◽  
Black Patients ◽  
Stage Iv Breast Cancer ◽  
White Patients

Purpose Overall, breast cancer mortality has been declining in the United States, but survival studies of patients with stage IV disease are limited. The aim of this study was to evaluate trends in and factors affecting survival in a large population-based cohort of patients with newly diagnosed stage IV breast cancer. Patients and Methods We searched the Surveillance, Epidemiology, and End Results registry to identify female patients with stage IV breast cancer diagnosed between 1988 and 2003. Patients were divided into three groups according to year of diagnosis (1988 to 1993, 1994 to 1998, and 1999 to 2003). Survival outcomes were estimated by the Kaplan-Meier method, and Cox models were fit to determine the characteristics independently associated with survival. Results We identified 15,438 patients. Median age was 62 years. Median follow-up was 16 months, 18 months, and 11 months in periods 1988 to 1993, 1994 to 1998, and 1999 to 2003, respectively. Median breast cancer–specific survival was 23 months. In the multivariate model, earlier year of diagnosis, grade 3 disease, increasing age, being unmarried, hormone receptor–negative disease, and no surgery were all independently associated with worse overall and breast cancer–specific survival. With each successive year of diagnosis, black patients had an increasingly greater risk of death compared with white patients (hazard ratio, 1.03; 95% CI, 1.00 to 1.06; P = .031). Conclusion The survival of patients with newly diagnosed stage IV breast cancer has modestly improved over time, but these data suggest that the disparity in survival between black and white patients has increased.

scholarly journals Breast conserving therapy and mastectomy revisited: Breast cancer-specific survival and the influence of prognostic factors in 129,692 patients

2017 ◽  
Vol 142 (1) ◽  
pp. 165-175 ◽  
Author(s):  
Mirelle Lagendijk ◽  
Marissa C. van Maaren ◽  
Sepideh Saadatmand ◽  
Luc J.A. Strobbe ◽  
Philip M.P. Poortmans ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Factors ◽  
Breast Conserving Therapy ◽  
Breast Cancer Specific Survival ◽  
Cancer Specific Survival
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