scholarly journals The Analysis of bcl-2 in Association with p53 and Ki-67 in Triple Negative Breast Cancer and Other Molecular Subtypes in Ghana

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Charity Ameh-Mensah ◽  
Babatunde Moses Duduyemi ◽  
Kweku Bedu-Addo ◽  
Elijah Atta Manu ◽  
Francis Opoku ◽  
...  

Background. Little is known about the role of apoptosis in the tumorigenesis and prognosis of breast cancer in Ghana. Chemotherapeutic drug efficacy partially relates to apoptosis induction, rendering it a vital target in cancer therapy with unique biomarker opportunities that have not been exploited. Aberrations in this pathway are central to tumorigenesis, tumor progression, overall tumor growth, and regression during treatment therapies. Antiapoptotic bcl-2 (gene) and p53 are known to play roles in apoptosis while Ki-67 is a proliferative marker. The aim of our study is to determine the association of bcl-2 (protein) with p53 and Ki-67 in 203 consecutive breast cancer cases over a 10-year period. Method. A retrospective cross-sectional study on archival FFPE tissue blocks over a 9-year period with abstraction of clinicopathologic data. Two hundred and three consecutive and suitable FFPE blocks were selected for tissue microarray (TMA) construction, and IHC (bcl-2 (protein), Ki-67, p53, cyclin D, pan cytokeratins A and E, ER, PR, and HER2/neu) was done. Expressions of bcl-2 (protein), p53, and Ki-67 were related to histological grade, lymphovascular invasion, and molecular subtypes. SPSS version 23 was used to analyze results. Results. Most of our cases were in the fifth decade of life (31%); invasive carcinoma of no special type (NST) was predominant (87%); histological grade III (38%) was the highest; and Luminal A (19.8%), Luminal B (9.9%), HER2 (16%), and TNBC (54.3%) constituted the molecular classes. bcl-2 expression was found in 38% of the cases. Our cases also showed mutation in p53 (36.7%) and ki-67 expression (62.5%). bcl-2 (protein) and p53 significantly correlated with Luminal B and TNBC ( p < 0.01 ). Ki-67 also correlated significantly with Luminal A and B and HER2 overexpression ( p < 0.01 ). Premenopausal age (40–49) and histological grade inversely correlated with bcl-2 (protein) expression. p53 statistically correlated with Ki-67 ( p < 0.05 ). Conclusion. Our results show high expression of bcl-2 (protein) suggesting an important role of apoptosis in Ghanaian breast cancer cases. bcl-2 (protein), p53, and Ki-67 expressions emerged interdependently from this research and can thus be manipulated in prediction and prognosis of breast cancers in our setting.

BMJ Open ◽  
2018 ◽  
Vol 8 (11) ◽  
pp. e021819
Author(s):  
Qin Li ◽  
Li Li ◽  
Xiaoyue Jiang ◽  
Qi Du ◽  
Yingrui Li ◽  
...  

ObjectivesThis study investigated the characteristics and prognostic values of traditional pathological parameters and advanced molecular subtypes in women with operable breast cancer in Beijing.DesignA retrospective study through case information enquiry or telephonic follow-up.SettingBeijing Friendship Hospital.Participants1042 patients with primary operable breast cancer between 2008 and 2012 were enrolled in the study.MeasuresThe characteristics and 5-year relapse rates according to the Nottingham Prognosis Index (NPI) and molecular subtypes were analysed.ResultsIn 1042 patients, the percentages of high histological grade, N1+N2, T2+T4 were 7.3%, 24.2%, 46.9%, respectively. In patients with invasive breast cancer, the percentages of auxiliary staging, positive margins, vascular invasion and nerve infiltration were 65.0%, 2.8%, 10.5% and 1.1%, respectively. The missing percentages of auxiliary staging, margins, vascular tumour invasion and nerve infiltration were 14.2%, 31.4%, 46.5% and 97.4%, respectively. The percentages of ER-positive, PR-positive, HER2-positive and Ki-67 high expression were 64.3%, 43.8%, 18.8% and 62.7%, respectively. The percentages of luminal A, luminal B, HER2-overexpression and basal-like breast cancers were 10.5%, 54.2%, 8.2% and 11.2%, respectively. Luminal A, luminal B and basal-like breast cancer subtypes were more common in the >60 years group, the 41–60 years group and the 20–40 years group, respectively. The 5-year relapse rates according to NPI were as follows: 6.2% in the low recurrence risk group, 10.4% in the moderate recurrence risk group and 12.9% in the high recurrence risk group. The 5-year relapse rates according to molecular subtypes were as follows: luminal A 4.0%, luminal B 7.0%, HER2-overexpression14.2%, basal-like 15.6%.ConclusionsReasonable analysis of traditional pathological parameters and advanced molecular subtypes in women with operable breast cancer in Beijing may be useful to guide precise treatment and predict prognosis.


2021 ◽  
Author(s):  
Dorsay Sadeghian ◽  
Hana Saffar ◽  
Pouya Mahdavi Sharif ◽  
Vahid Soleimani ◽  
Behnaz Jahanbin

Abstract Background: Currently, breast cancers are divided into four major molecular subtypes. The distinction between the luminal A and luminal B subtypes is mainly based on the cellular proliferation indices and is assessed by the Ki-67 scoring. Due to the limitations in the assessment and expression of Ki-67, we hypothesized that minichromosome maintenance protein 6 (MCM6) can be taken as a surrogate marker to differentiate molecular subtypes and aid in more precise grading of tumors. Methods: We performed a retrospective, cross-sectional study on 124 samples of breast cancer and 40 samples of normal breast tissue. Relevant clinical information was retrieved from the relevant Cancer Institute database.Results: MCM6 could discriminate between different histologic grades. The luminal B subtype exhibited a higher MCM6 score in comparison to luminal A (P=0.01). There were significantly higher MCM6 scores in the hormone receptor (HR) negative, in comparison to luminal breast cancers (P<0.001). MCM6 score had a significant correlation with the mitotic count (P<0.001).Conclusion: MCM6 can reliably differentiate luminal A and luminal B subtypes and was correlated with the mitotic counts. More studies are needed to standardize its assessment methods, determine more robust cut-off values, and evaluate its associations with prognostic features of breast cancer.


2021 ◽  
Vol 11 ◽  
Author(s):  
Kyoungmin Lee ◽  
Sung Hoon Sim ◽  
Eun Joo Kang ◽  
Jae Hong Seo ◽  
Heejung Chae ◽  
...  

Background: The role of chemotherapy for isolated locoregional recurrence (iLRR) of breast cancer has not been firmly established after local therapies.Methods: We performed a multicenter, retrospective analysis to evaluate the clinical implications of chemotherapy in breast cancer patients with HER2-negative iLRR.Results: Of a total of 277 patients, 146 (52.7%) received chemotherapy for iLRR. Median follow-up duration was 56.1 months. Eighty-six (31.0%) patients had luminal B-like and 100 (36.1%) had TNBC iLRR. There was a trend of longer disease free survival (DFS) in the chemotherapy group (4-year DFS: 70.4 vs. 59.5%, HR = 0.68, 95% CI 0.45–1.02, log-rank p = 0.059). When adjusted with clinically relevant factors, DFS was significantly prolonged with chemotherapy (adjusted HR = 0.61, 95% CI 0.40–0.94, p = 0.023). Subgroup analyses for DFS showed patients with disease free interval (DFI) &lt;5 years or prior chemotherapy had a benefit from chemotherapy (adjusted HR = 0.57, p = 0.018; adjusted HR = 0.51, p = 0.005, respectively). Regarding the molecular subtypes, a longer DFS with chemotherapy was observed both in luminal B-like (4-year DFS: 77.8 vs. 55.0%, HR = 0.51, 95% CI 0.27–0.99, log-rank p = 0.048) and in TNBC patients (4-year DFS: 61.9 vs. 42.8%, HR = 0.49, 95% CI 0.24–1.02, log-rank p = 0.056), but not in luminal A-like.Conclusions: The chemotherapy for iLRR of breast cancer should be individualized for each patient, considering DFI, prior chemotherapy, and molecular subtypes.


Author(s):  
Iris Rabinovich ◽  
Ana Paula Martins Sebastião ◽  
Rubens Silveira Lima ◽  
Cícero de Andrade Urban ◽  
Eduardo Schunemann Junior ◽  
...  

Breast cancer is a very heterogeneous disease. The intrinsic molecular subtypes can explain the intertumoral heterogeneity and the cancer stem cell (CSC) hypothesis can explain the intratumoral heterogeneity of this kind of tumor. CD44+/CD24- phenotype and ALDH1 expression are the major CSC markers described in invasive breast cancer. In the present study, 144 samples of invasive breast carcinoma, no special type were distributed in 15 tissue microarrays (TMA) and then evaluated for expression of the CD44+/CD24- phenotype and ALDH1 to understand the importance of these CSC markers and the clinical aspects of breast cancer. The samples were classified into four molecular subtypes according to clinicopathological criteria: Luminal A, Luminal B, HER2, and Basal-like. A statistical association was found between the molecular subtypes and the CSC markers, with HER2 the most frequent subtype for both markers. ALDH1 was also associated with other poor prognostic variables, such as a high histological grade and larger tumors, but it was not associated with the patients’ prognosis in this sample and nor was the CD44+/CD24- phenotype in a multivariate analysis. There are still many controversies about the role of these markers in breast cancer molecular subtypes. The identification of these populations of cells, through immunohistochemical markers, can help to better understand the CSC theory in clinical practice and, in the near future, contribute to developing new target therapies.    


2020 ◽  
Vol 19 ◽  
pp. 153303382092843
Author(s):  
Ling-Cheng Wang ◽  
Ling-Sheng Wang ◽  
Ai-Xia Li ◽  
Zhen-Zong Shi ◽  
Ya-Qiong Li ◽  
...  

Aim: The aim of this study is to characterize the effect of chemotherapy drug doxorubicin with neoadjuvant drug docetaxel for different molecular subtypes. Methods: A total of 83 patients with late-stage breast cancer were chosen to undergo treatment and compared to these patients to the combinational treatment to identify the molecular characteristics that can predict the responses. Results: Total response rate is 81.9% (68/83 patients). Among them, 7 patients show pathological complete response of 8.4%, 12 patients show clinical complete response of 14.5%, 49 patients show partial response of 59%, and 15 patients show stable disease of 18.1%. The comparison among different subtypes of breast cancer, including luminal A, luminal B, basal-like, and ERBB2+ subtypes, did not show statistical significant differences to the treatment of combinational treatment for the complete response rate, including pathological complete response and clinical complete response. Comparing with luminal A and luminal B subtypes, the ERBB2+ and basal-like subtypes have better complete response and response rate rates. The disease-free survival rate and overall survival rate at 29 months after treatment did not show statistical significant differences among different subtypes of patients with breast cancer. Conclusion: The molecular subtypes of breast cancer can predict responses to the combinational treatment of doxorubicin with docetaxel, and ERBB2+ and basal-like subtypes have better response rate and complete response rate. There is correlation of estrogen receptor and KI-67 level changes with response rate as well, where KI-67 high patients are more sensitive to the treatment.


2021 ◽  
Vol 16 (4) ◽  
pp. 35-40
Author(s):  
A. Kh. Ismagilov ◽  
D. R. Khuzina ◽  
A. S. Vanesyan ◽  
V. V. Zaysteva

One of the main priorities in modern oncology is the identification and clinical application of biomarkers that can be helpful in the diagnostics and prognostication of cancer. The aim of this article was to review biomarkers for early diagnosis and prediction of prognosis of breast cancer. There were reviewed three main groups of biomarkers in this article: familial breast cancer biomarkers with high and low penetration (BRCA1, BRCA2, TP53, etc.), biomarkers of breast cancer molecular subtypes (luminal A and luminal B, HER2/neu, basal and low in claudine) and biomarkers of early stage breast cancer progression (multigenic panels).


Mastology ◽  
2020 ◽  
Vol 30 (Suppl 1) ◽  
Author(s):  
Vanessa Monteiro Sanvido ◽  
Morgana Domingues da Silva ◽  
Patricia Zaideman Charf ◽  
Simone Elias ◽  
Afonso Celso Pinto Nazário

Introduction: Breast cancer is the second most common malignant neoplasm among women in Brazil and worldwide. Its incidence increases with age, especially in individuals older than 50 years. Mammography is the main screening test, has high sensitivity, and is the only method that has made an impact on mortality rate. Breast cancer is classified into molecular subtypes, based on immunohistochemical markers. The luminal A subtype (LA) presents estrogen receptor (ER) and progesterone receptor (PR) positive, HER2 negative, and low Ki-67 index. Luminal B (LB) shows ER and/or PR positive, HER2 negative, high Ki-67 index, or HER2 positive (luminal HER2). HER2 has HER2 overexpression and ER and PR negative. Triple-negative (TN) has ER, PR, and HER2 negative and high histological grade. Objective: To evaluate patient characteristics according to the molecular subtypes of breast carcinoma among individuals treated at the Hospital São Paulo – Universidade Federal de São Paulo. Method: This is a retrospective study based on the analysis of medical records of breast cancer cases from the Hospital São Paulo between 2013 and 2016. During this period, 235 patients were treated. Among them, 40% were classified as LA, 34% as LB, 8% as luminal HER2, 15% as TN, and 3% as HER2. The mean age was 57.6 years. The incidence of breast carcinoma was higher in women over 50 years of age in all subtypes: 75.2% for LA, 65% for LB, 58% for luminal HER2, 100% for HER2 overexpression, and 75.1% for TN. Regarding ethnicity, most women were white in all subtypes, accounting for 66.5% of cases. In all subtypes, the most common clinical complaint was nodule: 86% for LA, 86% for LB, 100% for HER2 overexpression, and 96% for TN. Among the mammographic findings, nodule was the most frequent in all subtypes. Luminal subtypes presented other findings, such as suspicious calcifications (14% for LA and 21% for LB), focal asymmetries (14% for LA and 5% for LB), and distortions (2% for LA and 3% for LB). Conclusion: Breast cancer has a higher incidence among Caucasian individuals and those aged 50 to 60 years. The clinical and imaging presentation of tumors is influenced by their molecular subtype: luminal subtypes have a greater diversity of findings and non-palpable lesions, while TN tumors usually manifest as palpable nodules.


Mastology ◽  
2020 ◽  
Vol 30 (Suppl 1) ◽  
Author(s):  
Vanessa Monteiro Sanvido ◽  
Morgana Domingues da Silva ◽  
Patricia Zaideman Charf ◽  
Gil Facina ◽  
Afonso Celso Pinto Nazário

Introduction: Invasive breast carcinoma represents a heterogeneous group of lesions that differ in their molecular and histological characteristics. Perou et al. evaluated breast tumors using the DNA microarray technique and classified them into four molecular subtypes: Luminal A (LA), Luminal B (LB), HER2 overexpression (HER2), and triple-negative (TN). Immunohistochemistry approximately identifies the subtypes. The TN subtype is negative for estrogen and progesterone receptors and HER2 protein. This subgroup is comprehensive, with 75% of them being basaloid, that is, cells with a molecular profile similar to that of myoepithelial cells and a high expression 5, 6, 14, and 17 cytokeratins, vimentin, and P-cadherin. These tumors tend to be more aggressive, have higher rates of cell proliferation, and, therefore, a worse prognosis. Clinically, triple-negative carcinomas are more strongly associated with younger patients, early local and distant recurrence. Given their rapid progression, they can be clinically diagnosed in the interval of screening tests. Objective: To compare clinical and radiological aspects of TN and other molecular subtypes of breast cancer at diagnosis. Method: The study retrospectively evaluated data collected from medical records of patients diagnosed with breast cancer and treated at the Hospital São Paulo from 2013 to 2016. Results: In the study period, 235 cases of breast cancer were diagnosed. The incidence in patients under 39 years was 4.2% for LA, 4.9% for LB, and 8.3% for TN. At diagnosis, 83% of patients with TN tumors had clinical complaints, of which 96% were nodules. In mammographies, TN presented as nodules in 100% of cases, LA in 68%, LB in 71%, and HER2 in 50%. Microcalcifications were identified in 14% of LA cases, 21% of LB, and 50% of HER2. TN had no cases of microcalcifications or asymmetries. Among the other subtypes, the diagnosis by physical examination represented 35% to 53% of cases. As to the staging at diagnosis, TN cases presented ≤2 cm tumors in 25% of cases. The LA, LB, and HER2 subtypes presented as ≤2 cm tumors, respectively, in 61%, 49.4%, and 43% of patients. Lymph node involvement by neoplasm at diagnosis occurred in 3.35%, 17.5%, 14.3%, and 33.3% of LA, LB, HER2, and TN cases, respectively. Conclusion: TN carcinomas affect a greater number of young patients, outside the screening age group. In our sample, TN tumors were diagnosed based on clinical complaints and showed no association with non-palpable breast lesions. TN is the subtype with the highest probability of interval tumors, untraceable by conventional exams, and, as a result, other screening options, such as serum assays, have been discussed.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14285-e14285
Author(s):  
Linxiaoxi Ma ◽  
Liang Guo ◽  
Shyamal Goswami ◽  
Xiaoming Zhang ◽  
Jiong Wu

e14285 Background: The treatment of breast cancer, one of the most common malignant tumors for female, focuses on the combined treatments based on subtypes including Luminal A, Luminal B, HER2 overexpression and triple negative. Given that none of those subtypes takes into consideration of immunological parameters, it is valuable to explore the biological characteristics and prognostic value of immune cells in breast caner. T follicular helper cells (Tfh cells) have been identified in different types of tumors with rare datas in breast cancer. One of them indicated the positive prognostic value of 8-gene Tfh signature. Exploration of Tfh cells may provide new clues to the potential immunotherapies in breast cancer. Methods: Freshly resected invasive breast cancer tissue from Fudan University Shanghai Cancer Center were collected during 06/2015 to 05/2017. Patients were divided into Luminal A (N = 61), Luminal B (HER2-) (N = 138), Luminal B (HER2+) (N = 72), HER2+ (non-luminal) (N = 57) and triple negative (N = 58) based on St Gallen International Expert Consensus. Results: A subpopulation of PD1hiCD4+ T cells in the tumor tissues of breast cancer was identified as Tfh-like cells, with the specific expression of Bcl-6 and CXCL13, confirmed by IHC. Phenotypes of those cells were checked by flow cytometry. Tfh-like cells were of a high level of ICOS but negative for CXCR5, suggesting that they were atypical Tfh cells. Data showed that high grade (N = 166; mean±SEM, 17.62±0.87) compared with low grade (N = 220; mean±SEM, 12.41±0.46) or high Ki-67 level (N = 300; mean±SEM, 15.38±0.58) with low Ki-67 level (N = 86; mean±SEM, 12.10±0.67), and negative ER expression (N = 115; mean±SEM, 17.47±1.05) compared with positive ER expression (N = 271; mean±SEM, 13.46±0.50) or negative PR expression (N = 177; mean±SEM, 16.87±0.83) compared with positive PR expression (N = 209; mean±SEM, 12.77±0.50) was associated with higher frequency of Tfh-like cells (P < 0.01 to all). Patients with triple negative had higher frequency of Tfh-like cells than those with Luminal A (difference, 6.83; P = 0.0006) and Luminal B (HER2-) (difference, 4.61; P = 0.0124). Patients with HER2+ (non-luminal) had higher frequency of Tfh-like cells than those with Luminal A (difference, 5.34; P = 0.0146). These results indicate that higher frequency of Tfh-like cells could have negative prognostic influence. Conclusions: Our study defined a PD1hiBcl6+CXCL13+CD4+ T cell subpopulation, which specifically secretes cytokine IL-21 as Tfh-like cells. Higher frequency of Tfh-like cells is more likely to be seen in patients with poor prognosis.


2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
E. Atta Manu ◽  
K. Bedu-Addo ◽  
N. A. Titiloye ◽  
C. Ameh-Mensah ◽  
F. Opoku ◽  
...  

Background. Immunohistochemical assessment of breast cancer and stratification into the basic molecular subtypes afford a much deeper insight into the biology of breast cancer, while presenting with opportunities to exploit personalized, targeted treatment. Traditionally, the oestrogen, progesterone, and epidermal growth factor receptors are assessed. MUC1, a transmembrane mucin, has been demonstrated a potential prognostic and metastatic marker in breast cancer. However, there have been a limited number of studies addressing the predictive and prognostic features of MUC1 in African breast cancer. This study aims at addressing the expression profiles of MUC1 and other biomarkers in Ghanaian breast cancer and determines its predictive and prognostic characteristics, in relation to other clinicopathological features. Methods. Haematoxylin and eosin (H&E) slides of breast cancer cases were reviewed and 203 suitable cases were selected for tissue microarray (TMA) construction and immunohistochemistry. Anti-ER, PR, HER2, Ki-67, and MUC1 antibodies were used. Results from the immunostaining were analysed using SPSS version 23. Results. About 59% of cases expressed MUC1. Majority of cases in the study showed a lack of expression of all three traditional markers (29% expressed ER, 10.9% PR, and 20.7% HER2). Ki-67 index were 62.1% (low), 16.5% (moderate), and 21.4% (high). MUC1 expressions among the molecular classes were luminal A (60.7%), luminal B (68.8%), HER2 overexpression (87.5%), and triple negative (56.6%). There were significant associations between MUC1 and HER2 overexpression (p=0.01) and triple negative (p<0.01). Conclusion. The high proportion of breast cancer cases expressing MUC1, as well as its association with the two most aggressive molecular classes, indicate a substantial role in the biology of breast cancer in our cohort, and it is an indication of poor prognosis.


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