Statistical partitioning of Ki-67 distribution can refine Molecular Classifica-tion of invasive Breast Carcinoma (Preprint)

BACKGROUND Breast carcinoma is one of the most common histological types of Breast Cancer, exploring a new approach that allows to do a quantitative description in order to characterize its heterogeneity and refine its classification is one of the main interests for pathologists. OBJECTIVE The purpose of our study is to explore further statistically significant subdivisions beyond breast cancer molecular classification that is routinely established in pathology departments. METHODS We conducted a 5-year retrospective study on 1266 invasive breast carcinomas of moroccan pa-tients, collected at the Pathology Department of Ibn-Rochd University Hospital in Casablanca, and followed at King MohammedVI National Centre for the Treatment of Cancers. We elaborated an Estimation-Maximization clustering, based on the main Breast cancer prognosis biomarkers: Ki-67, HER2, oestrogen and progesterone receptors, evaluated by Immunohistochemistry. RESULTS Each molecular subgroup could be partitioned into two further subdivisions: Cluster1, with average Ki-67 of 16.26%(±11.9) across all molecular subgroups and higher frequency within luminal sub-groups, and Cluster2, with average Ki-67 of 68.8%(±18) across all molecular subgroups; and higher frequency in HER2 as well as in triple negative subgroups. Overall Survival of the two clusters was significantly different, with 5-year rates of 52 and 37 months for Cluster1 and Cluster2, respectively (p=0.000001). Moreover, patient survival within the same molecular subgroup varied remarkably depending on cluster membership. Three independent datasets (Algerian, TCGA-BRCA and METABRIC) were also analysed to assess the reproducibility of this new “2-clusters partition” through several clustering methods and validation measures. Two different al-gorithms to evaluate the prognostic importance, VSURF and MinimalDepth, confirmed that this new subdivision is able to predict patient survival better than several histoprognostic features. CONCLUSIONS Our results highlight a new refinement of the breast cancer molecular classification and provide a simple and improved way to classify tumors that could be applied in low to medium income countries. This is the first study of its kind addressed in an African context.

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Determination of Hormone Receptors, Human Epidermal Growth Factor Receptor 2 and Ki67 Status in Invasive Breast Carcinoma: A Concordance Study between Immunohistochemistry, Fluorescence in Situ Hybridization, and GeneXpert® Breast Cancer STRAT4 Assay

10.21203/rs.3.rs-1044271/v1 ◽

2021 ◽

Author(s):

rajaa elaje ◽

Abdellah Naya ◽

Ayoub KHOAJA ◽

Younes Zaid ◽

Mounia Oudghiri ◽

...

Keyword(s):

Breast Cancer ◽

In Situ Hybridization ◽

Mrna Expression ◽

Hormone Receptors ◽

Therapy Response ◽

Cancer Prognosis ◽

University Hospital ◽

Automated System ◽

Ki 67

Abstract BackgroundThe accurate assessment of hormone receptors (ER and PR), HER2 and Ki-67 proliferative index provides meaningful information about breast cancer prognosis and prediction of therapy response. Immunohistochemistry, the most common method for evaluating these prognostic biomarkers, can be impacted by numerous variabilities due to pre-analytical/analytical factors and subjective interpretation by pathologists. The Xpert® Breast Cancer STRAT4, a RT-qPCR based system, can be used to classify breast invasive carcinomas based on the assessment of these 4 biomarkers. In this study, we investigated the accuracy of RT-qPCR based mRNA expression levels in a closed, single-use cartridge, automated system compared with the current gold standard, immunohistochemistry (IHC), and fluorescent in situ hybridization (FISH) for HER2 equivocal cases.Methods We evaluated ESR1, PGR, ERBB2 and MKi67 mRNA expression by Xpert Breast Cancer STRAT4 and ER, PR, HER2 and Ki67 by IHC (FISH for HER2 IHC 2+) in 200 formalin-fixed paraffin-embedded (FFPE) tissue blocks with invasive breast cancer, collected from the Pathology Department of Casablanca Ibn Rochd University Hospital.Results Concordance between Xpert ® Breast Cancer STRAT4 and IHC was 93.5% for ER, 83.51% for PR, 95% for HER2 (92% for IHC+FISH), and 81.20% for Ki67 (excluding intermediate IHC Staining 10 ≤ %IHC <20). The simple Kappa coefficient was, for ER, 0.830 (P < 0, 0001), 0.565 (P < 0, 0001) for PR, 0.838 (P < 0, 0001) for HER2-IHC, 0.771 (P< 0, 0001) for HER2 IHC+FISH and, for, Ki67, 0.458 (P < 0, 0001).Conclusions We demonstrated globally a high concordance between centrally assessed IHC, IHC+FISH and mRNA measurements of ER/ESR1 and HER2/ERBB2, and a moderate agreement between PR/PGR and Ki67/MKi67. These findings provide an additional, objective, and quantitative assessment of tumor receptor status in breast cancer.

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The Pattern of Proline, Glutamic Acid, and Leucine-Rich Protein 1 Expression in Chinese Women with Primary Breast Cancer

The International Journal of Biological Markers ◽

10.5301/jbm.5000078 ◽

2014 ◽

Vol 29 (1) ◽

pp. e1-e7 ◽

Cited By ~ 1

Author(s):

Yanzhi Zhang ◽

Peng Wang ◽

Mumu Shi ◽

Hironobu Sasano ◽

Monica S.M. Chan ◽

...

Keyword(s):

Breast Cancer ◽

Glutamic Acid ◽

Primary Breast Cancer ◽

Chinese Women ◽

Cancer Prognosis ◽

Clinicopathological Parameters ◽

Breast Cancers ◽

Breast Cancer Patients ◽

Ki 67 ◽

Her 2

Background Disparities of biomarkers’ expression in breast cancer across different races and ethnicities have been well documented. Proline, glutamic acid, and leucine-rich protein 1 (PELP1), a novel ER coregulator, has been considered as a promising biomarker of breast cancer prognosis; however, the pattern of PELP1 expression in Chinese women with breast cancer has never been investigated. This study aims to provide useful reference on possible racial or ethnic differences of PELP1 expression in breast cancer by exploring the pattern of PELP1 expression in Chinese women with primary breast cancer. Methods The expression of PELP1 in primary breast cancer samples from 130 Chinese female patients was detected by immunohistochemistry and correlated to other clinicopathological parameters; for comparison, the expression of PELP1 in 26 benign breast fibroadenomas was also examined. Results The overall value of the PELP1 H-score in breast cancer was significantly higher than that in breast fibroadenoma (p<0.001). In our breast cancer patients, the ER/HER-2-positive group had significantly higher PELP1 H-scores than their negative counterparts (p=0.003 for ER and p=0.022 for HER-2); the Ki-67-high group also showed significantly higher PELP1 H-scores than the Ki-67-low group (p=0.008). No significant association between PELP1 H-scores and other clinicopathological parameters was found. Finally, the PELP1 H-score in breast cancers of the luminal B subtype was significantly higher than that in the triple negative subtype (p=0.002). Conclusion Overexpression of PELP1 in Chinese women with primary breast cancer appears to be associated with biomarkers of poor outcome; these results are similar to other reports based on Western populations.

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Prognostic Signicance of Cellular Iron Metabolism in Breast Cancer

Pakistan BioMedical Journal ◽

10.52229/pbmj.v1i1.35 ◽

2018 ◽

Vol 1 (1) ◽

Author(s):

Rizwan Ullah Khan ◽

Amber Hassan ◽

Imrana Tanvir ◽

Kashifa Ehsan

Keyword(s):

Breast Cancer ◽

Breast Carcinoma ◽

Ki 67 ◽

Luminal B ◽

Cellular Iron ◽

Menopausal Women ◽

New Strategy ◽

Poorly Differentiated ◽

Well Differentiated ◽

Post Menopausal

Breast carcinoma is among the most common malignancy in women. Abstract:Original ArticleAim of the present study was to evaluate the prognostic signicance of iron expression in the biopsies of patients with breast cancer Objective:24 breast biopsies were studied. 19 cases were poorly differentiated, 5 cases were moderately differentiated and there was no well differentiated case. Iron, Estrogen receptor (ER), Progesterone receptor (PR), HER2 and Ki-67 immunohistochemical staining was performed for all these cases. Methods: Among the 5 moderately differentiated cases, 3 (60%) were positive for iron staining and among 19 poorly differentiated cases, 11 cases (57.89%) were positive. More iron positive cases (7 out of 14) were triple positive belonging to Luminal B class. Out of 14 iron positive cases, 11 were positive for HER2, 10 for ER, 9 for PR and all positive for Ki-67. Results: Iron deciency in premenopausal and overload in post-menopausal women can contribute to the development of breast carcinoma. So, iron can be considered as a cheap and effective marker for the prognosis of breast cancer. Association between a rise in iron levels and HER2 expression may provide new strategy for breast cancer treatment.

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Correlation of manual semi-quantitative and automated quantitative Ki-67 proliferative index with OncotypeDXTM recurrence score in invasive breast carcinoma

Breast Disease ◽

10.3233/bd-201011 ◽

2021 ◽

pp. 1-11

Author(s):

Brian S. Finkelman ◽

Amanda Meindl ◽

Carissa LaBoy ◽

Brannan Griffin ◽

Suguna Narayan ◽

...

Keyword(s):

Breast Cancer ◽

Breast Carcinoma ◽

Hot Spot ◽

Recurrence Score ◽

Invasive Breast Carcinoma ◽

Chemotherapy Response ◽

Scoring Method ◽

Cancer Proliferation ◽

Ki 67 ◽

Breast Cancer Chemotherapy

BACKGROUND: Ki-67 immunohistochemistry (IHC) staining is a widely used cancer proliferation assay; however, its limitations could be improved with automated scoring. The OncotypeDXTM Recurrence Score (ORS), which primarily evaluates cancer proliferation genes, is a prognostic indicator for breast cancer chemotherapy response; however, it is more expensive and slower than Ki-67. OBJECTIVE: To compare manual Ki-67 (mKi-67) with automated Ki-67 (aKi-67) algorithm results based on manually selected Ki-67 “hot spots” in breast cancer, and correlate both with ORS. METHODS: 105 invasive breast carcinoma cases from 100 patients at our institution (2011–2013) with available ORS were evaluated. Concordance was assessed via Cohen’s Kappa (κ). RESULTS: 57/105 cases showed agreement between mKi-67 and aKi-67 (κ 0.31, 95% CI 0.18–0.45), with 41 cases overestimated by aKi-67. Concordance was higher when estimated on the same image (κ 0.53, 95% CI 0.37–0.69). Concordance between mKi-67 score and ORS was fair (κ 0.27, 95% CI 0.11–0.42), and concordance between aKi-67 and ORS was poor (κ 0.10, 95% CI −0.03–0.23). CONCLUSIONS: These results highlight the limits of Ki-67 algorithms that use manual “hot spot” selection. Due to suboptimal concordance, Ki-67 is likely most useful as a complement to, rather than a surrogate for ORS, regardless of scoring method.

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Relationship between Clinicopathologic Variables in Breast Cancer Overall Survival Using Biogeography-Based Optimization Algorithm

BioMed Research International ◽

10.1155/2019/2304128 ◽

2019 ◽

Vol 2019 ◽

pp. 1-12

Author(s):

Li-Yeh Chuang ◽

Guang-Yu Chen ◽

Sin-Hua Moi ◽

Fu Ou-Yang ◽

Ming-Feng Hou ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Predictive Accuracy ◽

Cancer Prognosis ◽

University Hospital ◽

Health Concern ◽

Survival Models ◽

Survival Prediction ◽

Prediction Ability ◽

Minimum Number

Breast cancer is the most common cancer among women and is considered a major public health concern worldwide. Biogeography-based optimization (BBO) is a novel metaheuristic algorithm. This study analyzed the relationship between the clinicopathologic variables of breast cancer using Cox proportional hazard (PH) regression on the basis of the BBO algorithm. The dataset is prospectively maintained by the Division of Breast Surgery at Kaohsiung Medical University Hospital. A total of 1896 patients with breast cancer were included and tracked from 2005 to 2017. Fifteen general breast cancer clinicopathologic variables were collected. We used the BBO algorithm to select the clinicopathologic variables that could potentially contribute to predicting breast cancer prognosis. Subsequently, Cox PH regression analysis was used to demonstrate the association between overall survival and the selected clinicopathologic variables. C-statistics were used to test predictive accuracy and the concordance of various survival models. The BBO-selected clinicopathologic variables model obtained the highest C-statistic value (80%) for predicting the overall survival of patients with breast cancer. The selected clinicopathologic variables included tumor size (hazard ratio [HR] 2.372, p = 0.006), lymph node metastasis (HR 1.301, p = 0.038), lymphovascular invasion (HR 1.606, p = 0.096), perineural invasion (HR 1.546, p = 0.168), dermal invasion (HR 1.548, p = 0.028), total mastectomy (HR 1.633, p = 0.092), without hormone therapy (HR 2.178, p = 0.003), and without chemotherapy (HR 1.234, p = 0.491). This number was the minimum number of discriminators required for optimal discrimination in the breast cancer overall survival model with acceptable prediction ability. Therefore, on the basis of the clinicopathologic variables, the survival prediction model in this study could contribute to breast cancer follow-up and management.

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The role of MRI in predicting Ki-67 in breast cancer: preliminary results from a prospective study

Tumori Journal ◽

10.5301/tj.5000619 ◽

2018 ◽

Vol 104 (6) ◽

pp. 438-443 ◽

Cited By ~ 2

Author(s):

Corrado Caiazzo ◽

Rosa Di Micco ◽

Emanuela Esposito ◽

Viviana Sollazzo ◽

Maria Cervotti ◽

...

Keyword(s):

Breast Cancer ◽

Breast Mri ◽

Cancer Prognosis ◽

Time Signal ◽

Local Health ◽

Ki 67 ◽

Contrast Enhanced ◽

Response To Chemotherapy ◽

The Mean ◽

The Relationship

Purpose: In the last decade contrast-enhanced magnetic resonance imaging (MRI) has gained a growing role as a complementary tool for breast cancer diagnosis. Currently the relationship between the kinetic features of a breast lesion and pathologic prognostic factors has become a popular field of research. Our aim is to verify whether breast MRI could be considered a useful tool to predict Ki-67 score, thus resulting as a breast cancer prognosis indicator. Methods: From June to December 2014, we enrolled patients with breast cancer who underwent preoperative dynamic contrast-enhanced MRI at the local health agency. We analyzed the time-signal intensity curves calculating the mean values of the following parameters: the basal enhancement (Ebase), the enhancement ratio (ENHratio), the maximum enhancement (Emax), and the steepest slope of the contrast enhancement curve (Smax). Scatterplots and Pearson correlation test were used to investigate the eventual associations among these parameters. Results: A total of 27 patients underwent breast MRI during the study period. The mean ± SD Ki-67 percentage was 27.03 ± 16.8; the mean Emax, Smax, Ebase, and ENHratio were 433.9 ± 120.2, 267.3 ± 96.8, 165.5 ± 77.1, and 187.1 ± 94.8, respectively. Scatterplots suggest a positive correlation between Ki-67 and both Emax and Smax. The correlation tests between Ki-67 and Emax, Ki-67 and Smax showed statistical significance. Conclusions: Our preliminary data suggest that enhancement pattern is closely linked to breast cancer proliferation, thus proving the relationship between more proliferating tumors and more rapidly enhanced lesions. This is hypothesis-generating for further studies aimed at promoting breast MRI in the early estimation of cancer prognosis and tumor in vivo response to chemotherapy.

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STUDY ON TWO YEAR SURVIVAL OF STAGE II AND STAGE III BREAST CARCINOMA IN EASTERN INDIA WITH SPECIAL REFERANCE TO PROGNOSTIC MARKERS HER-2/NEU, ER, PR AND Ki-67.

International Journal of Medical and Biomedical Studies ◽

10.32553/ijmbs.v4i4.1092 ◽

2020 ◽

Vol 4 (4) ◽

Author(s):

Deepika Pandey ◽

Rajesh kumar Sinha ◽

Gautam Mandal

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Breast Carcinoma ◽

Triple Negative ◽

Disease Free Survival ◽

Stage Ii ◽

Stage Iii ◽

Ki 67 ◽

Important Indicator ◽

Her 2

Breast cancer is one of the most commonly diagnosed malignancies and leading cause of cancer death in women over the world and the second most common cancer in females in India. Length of survival of cancer patients is an important indicator for knowing the outcome of treatment in any study. As the disease burden and mortality rate is very high, knowing the factors that influence survival rates among women with breast cancer may help design early detection and improve treatment. The immunohistochemistry plays a very important role in prognostication and treatment determination. Aim: This study aims to correlate the various relevant prognostic pattern like reactivity pattern of ER,PR,Her-2/Neu ,ki-67 and 2-yr overall survival. Material and method: The proposed study was a cross sectional study with mostly prospective observation and with some retrospective observation, included 74 patients of stage II and stage III breast carcinoma who underwent MRM in Chittaranjan National Cancer Institute from 2017-2018. The various clinical and histopathological prognostic parameters with Estrogen/ Progesterone hormone receptors and Human epidermal growth factor receptor (Her-2/Neu) status in invasive breast carcinoma patients were studied and correlated. Result: 58.1%, 54.1% and 35.1% of the cases were ER, PR and Her-2/neu positive respectively. 89.2% of cases had Ki-67 level >20%. Her-2 neu negative, ER negative and KI-67>20% were found to be significant factors for mortality. Maximum (66.7%) of patients with recurrence and maximum (53.8%) patients who died in study period had triple negative breast cancer. Triple negative tumours have poor survival as compared to ER + PR + and HER-2/Neu +ve tumours. Disease free survival and overall survival of the patients with Ki-67< 20% was better than that of patients with Ki-67>20% (100%). Keywords: Breast cancer, Invasive ductal carcinoma, ER,PR,HER-2/Neu , Ki-67 , Two year survival.

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Histology of Luminal Breast Cancer

Breast Care ◽

10.1159/000509025 ◽

2020 ◽

Vol 15 (4) ◽

pp. 327-336

Author(s):

Ramona Erber ◽

Arndt Hartmann

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Breast Carcinoma ◽

Expression Profiling ◽

Molecular Subtypes ◽

Luminal Breast Cancer ◽

Pathological Features ◽

Histological Subtypes ◽

Ki 67 ◽

Clinical And Pathological Features

Background: Invasive breast cancer (IBC) can be categorized into prognostic and predictive molecular subtypes (including luminal breast cancer) using gene expression profiling. Luminal IBC comprises a variety of histological subtypes with varying clinical and pathological features. Summary: IBC of no special subtype is the most common histological subtype in general and likewise within luminal IBC. Classical invasive lobular breast cancer, typically clustering into luminal subgroup, is characterized by discohesive growth and loss of E-cadherin expression. Infrequent, morphologically distinct luminal IBC subtypes are tubular, invasive cribriform, mucinous, and invasive micropapillary carcinomas. Breast carcinoma with apocrine differentiation, with characteristic expression of androgen receptor (AR), often clusters into the luminal AR category. Rarely, neuroendocrine neoplasms of the breast can be seen. IBC of the male breast usually matches with the luminal subtype. Key Messages: Independently from histological subtypes, invasive breast cancer (IBC) can be divided into molecular subtypes based on mRNA gene expression levels. Using this molecular subtyping, risk scores based on gene expression profiling (established for hormone receptor-positive, HER2-negative IBC), grading, and Ki-67 index, prognosis of patients with luminal breast cancer and response to chemotherapy can be predicted. In routine diagnostics, the expression of estrogen receptor (ER) and progesterone receptor (PR), HER2 status, and the proliferation rate (Ki-67) are used to determine a surrogate (molecular-like) subtype. Within luminal(-like) IBC, no special subtype and invasive lobular breast carcinoma are the most common histological subtypes. Other rare histological subtypes (e.g., tubular carcinoma) should be recognized due to their distinct clinical and pathological features.

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