The prognostic significance of early stage lymph node positivity in operable invasive breast carcinoma: number or stage

2012 ◽  
Vol 65 (7) ◽  
pp. 624-630 ◽  
Author(s):  
Emad A Rakha ◽  
David Morgan ◽  
Douglas Macmillan
Keyword(s):  
Breast Cancer ◽  
Prognostic Value ◽  
Independent Predictor ◽  
Early Stage ◽  
Histological Grade ◽  
Tumour Size ◽  
Prognostic Significance ◽  
Absolute Number ◽  
Consecutive Series ◽  
Cancer Specific Survival

AimThe earlier detection of breast cancer through mammographic screening has resulted in a shift in stage distribution with patients who are node-positive tending to present with a lower number of positive lymph nodes (LN). This study aims to assess the prognostic value of absolute number of positive nodes in the pN1 TNM stage (1–3 positive LN) and whether the prognostic value of the number of nodes in this clinically important stage justifies its consideration in management decisions.MethodsThis study is based on a large and well-characterised consecutive series of operable breast cancer (3491 cases), treated according to standard protocols in a single institution, with a long-term follow-up.ResultsLN stages and the absolute number of LN are associated with both breast cancer specific survival (BCSS) and distant metastasis free survival (DMFS). In the pN1 stage, patients with three positive LN (14% of pN1) show shorter BCSS (HR=1.9, (95% CI 1.3 to 2.6)) and shorter DMFS (HR=2.2, (95% CI 1.6 to 2.9)) when compared with one and/or two positive nodes. This effect is noted in the whole series as well as in different subgroups based on tumour size (pT1c and pT2), histological grade (grade 2 and 3), vascular invasion and oestrogen receptor status (both positive and negative). Multivariable analyses showed that three positive LN, compared with one and two positive LN, are an independent predictor of shorter BCSS and DMFS.ConclusionThe number of LN in the pN1 stage yielded potentially informative risk assignments with three positive LN providing an independent predictor of poorer outcome.

scholarly journals Age-Related Biology of Early-Stage Operable Breast Cancer and Its Impact on Clinical Outcome

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1417
Author(s):  
Binafsha M. Syed ◽  
Andrew R. Green ◽  
Emad A. Rakha ◽  
David A.L. Morgan ◽  
Ian O. Ellis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Histological Grade ◽  
Survival Rates ◽  
Growth Factor Receptor ◽  
Progesterone Receptors ◽  
Biological Characteristics ◽  
Cancer Specific Survival ◽  
Age Related ◽  
Significant Difference

As age advances, breast cancer (BC) tends to change its biological characteristics. This study aimed to explore the natural progression of such changes. The study included 2383 women with clinically T0-2N0-1M0 BC, managed by primary surgery and optimal adjuvant therapy in a dedicated BC facility. Tissue micro-arrays were constructed from their surgical specimens and indirect immunohistochemistry was used for analysis of a large panel (n = 16) of relevant biomarkers. There were significant changes in the pattern of expression of biomarkers related to luminal (oestrogen receptor (ER), progesterone receptors (PgR), human epidermal growth factor receptor (HER-2), E-cadherin, MUC1, bcl2 CK7/8, CK18 and bcl2) and basal (CK5/6, CK14, p53 and Ki67) phenotypes, lymph node stage, histological grade and pathological size when decade-wise comparison was made (p < 0.05). The ages of 40 years and 70 years appeared to be the milestones marking a change of the pattern. There were significantly higher metastasis free and breast cancer specific survival rates among older women with ER positive tumours while there was no significant difference in the ER negative group according to age. Biological characteristics of BC show a pattern of change with advancing age, where 40 years and 70 years appear as important milestones. The pattern suggests <40 years as the phase with aggressive phenotypes, >70 years as the less aggressive phase and 40–70 years being the transitional phase.

scholarly journals Prognostic significance of CTNNB1 mutation in early stage endometrial carcinoma: a systematic review and meta-analysis

2022 ◽  
Author(s):  
Antonio Travaglino ◽  
Antonio Raffone ◽  
Diego Raimondo ◽  
Sabrina Reppuccia ◽  
Alessandro Ruggiero ◽  
...  
Keyword(s):  
Systematic Review ◽  
Endometrial Carcinoma ◽  
Prognostic Value ◽  
Early Stage ◽  
Meta Analysis ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Absolute Number ◽  
Molecular Profile ◽  
Endometrioid Endometrial Carcinoma

Abstract Background In the last years, mutations in the exon 3 of CTNNB1 have emerged as a possible prognostic factor for recurrence in early stage endometrioid endometrial carcinoma, especially in cases with no specific molecular profile (NSMP). Objective To define the prognostic value of CTNNB1 mutations in early stage endometrioid endometrial carcinoma, through a systematic review and meta-analysis. Methods Electronic databases were searched from their inception to November 2020 for all studies assessing the prognostic value of CTNNB1 mutation in early stage (FIGO I–II) endometrioid endometrial carcinoma. Odds ratio (OR) for tumor recurrence and hazard ratio (HR) for disease-free survival (DFS) were calculated with a significant p value < 0.05. Results Seven studies with 1031 patients were included. Four studies were suitable for meta-analysis of OR and showed significant association between CTNNB1 mutation and the absolute number of recurrence (OR = 3.000; p = 0.019); the association became stronger after excluding patients with known molecular status other than NSMP (HR = 5.953; p = 0.012). Three studies were suitable for meta-analysis of HR and showed no significant association between CTNNB1 mutation and decreased DFS (HR = 1.847; p = 0.303); the association became significant after excluding patients with known molecular status other than NSMP (HR = 2.831; p = 0.026). Conclusion CTNNB1 mutation is significantly associated with recurrence in early stage endometrioid endometrial carcinomas, especially in the NSMP, appearing potentially useful in directing adjuvant treatment.

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 Cancer Grade Model: a multi-gene machine learning-based risk classification for improving prognosis in breast cancer

2021 ◽  
Author(s):  
E. Amiri Souri ◽  
A. Chenoweth ◽  
A. Cheung ◽  
S. N. Karagiannis ◽  
S. Tsoka
Keyword(s):  
Breast Cancer ◽  
Machine Learning ◽  
Clinical Decision Making ◽  
Histological Grade ◽  
Tumour Size ◽  
Clinical Decision ◽  
Gene Signature ◽  
Risk Classification ◽  
Breast Cancers ◽  
Grade 3

Abstract Background Prognostic stratification of breast cancers remains a challenge to improve clinical decision making. We employ machine learning on breast cancer transcriptomics from multiple studies to link the expression of specific genes to histological grade and classify tumours into a more or less aggressive prognostic type. Materials and methods Microarray data of 5031 untreated breast tumours spanning 33 published datasets and corresponding clinical data were integrated. A machine learning model based on gradient boosted trees was trained on histological grade-1 and grade-3 samples. The resulting predictive model (Cancer Grade Model, CGM) was applied on samples of grade-2 and unknown-grade (3029) for prognostic risk classification. Results A 70-gene signature for assessing clinical risk was identified and was shown to be 90% accurate when tested on known histological-grade samples. The predictive framework was validated through survival analysis and showed robust prognostic performance. CGM was cross-referenced with existing genomic tests and demonstrated the competitive predictive power of tumour risk. Conclusions CGM is able to classify tumours into better-defined prognostic categories without employing information on tumour size, stage, or subgroups. The model offers means to improve prognosis and support the clinical decision and precision treatments, thereby potentially contributing to preventing underdiagnosis of high-risk tumours and minimising over-treatment of low-risk disease.

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.

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