scholarly journals Breast cancer immunophenotype and its relationship with haematopoiesis

2021 ◽  
Vol 23 (2) ◽  
pp. 275-279
Author(s):  
Denis A. Ryabchikov ◽  
Svetlana V. Chulkova ◽  
Farhad A. Shamilov ◽  
Nail V. Chanturia ◽  
Sergey D. Zheltikov ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Tumor Cells ◽  
Triple Negative ◽  
Molecular Subtypes ◽  
Receptor Expression ◽  
Luminal Subtype ◽  
Expression Levels ◽  
Luminal B ◽  
Hla Dr

Background. The applying of immunotherapeutic approaches in cancer treatment requires a deep and comprehensive understanding of the tumor biological characteristics. In this regard, the study of the tumor immunophenotype is one of the leading scientific directions. The major histocompatibility complex molecules are considered to be the promising markers of the immunotherapy effectiveness prediciton. Aim. To research tumor immunophenotype in different molecular subtypes of breast cancer (BC). Materials and methods. The study included 99 patients with BC. Luminal cancer 84.8% (n=83), Erb-B2 overexpressing (HER2+) subtype 5.0% of cases (n=5), triple-negative BC 10.2% (n=10). Stages: T1 (51.5%), T2 (44.4%), T3 (2.0%). Lymph node metastases (N+) were present in 39.4% (n=39) of cases. Grade of malignancy: 80.8% (G2). Samples of tumor tissue and bone marrow were examined. Immunophenotyping of the tumor was carried out on cryostat sections by the method of immunofluorescense. Antibodies to HLA-I, HLA-DR, CD71 were used and were directly conjugated to fluorochromes PE, FITC, PE-Cy5. The bone marrow was examined by a morphological method using light microscopy. Statistical data processing was performed using the IBM-SPSS statistics v2.1. Results. In 50.8% (31/61) cases of luminal BC (LBC), the HLA-I molecule is absent on the membrane or is expressed by single tumor cells. A decrease in HLA-I expression levels in the luminal subtype was combined with the absence of HLA-DR antigens, which was found in 63.1% of cases. A higher frequency of HLA-I expression is observed in the Erb-B2 overexpressing BC, the differences are insignificant. Expression of CD71 was defected in 67.8% (40/59) of the studied samples of LBC. CD71 was expressed on the surface of most tumor cells (70%) in triple-negative BC. There were no statistically significant differences between the studied molecular subtypes of BC. Analysis of the luminal subtypes revealed that CD71 expression was observed much more often in luminal B subtype: 76.5% (n=26) and 75% (n=3) versus 52.4% (n=11). HLA-I expressing luminal cancer were characterized by higher levels of erythroid precursors (polychromatophilic normoblasts 9.00.9 and 5.80.8%, p=0.0017; oxyphilic normoblasts (7.90.7 and 5.30.6%, p=0.008), an increase in the amount of erythroid germ cells (17.71.5 and 11.61.5%, р=0.009) and an increased content of myelokaryocytes (93.117.1 thousand/l versus 57.39.0 thousand/l, p=0.083). Conclusion. In LBC a decrease in the expression levels of HLA-I class molecules was noted in combination with the absence of HLA-DR antigens on the membrane of tumor cells, which was observed in more than half of the analyzed samples. The frequency of expression in triple-negative cancer is higher than in the luminal subtype. There were no statistically significant differences between molecular subtypes by the level of expression of HLA-I and II class molecules. Transferrin receptor expression has been reported in most cases of triple-negative BC subtype. The interconnection between the expression of HLA-I histocompatibility molecules and hematopoetic parameters in LBC has been established.

scholarly journals Inflammatory Breast Cancer: Clinical Characteristics and Influence of Molecular Subtypes on Treatment Response

2021 ◽  
Vol 107 (1_suppl) ◽  
pp. 12-12
Author(s):  
D Aissaoui ◽  
M Bohli ◽  
R Ben Amor ◽  
J Yahyaoui ◽  
A Hamdoun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Treatment Response ◽  
Inflammatory Breast Cancer ◽  
Hormone Receptor ◽  
Triple Negative ◽  
Molecular Subtypes ◽  
Luminal A ◽  
Her2 Positive ◽  
Luminal B ◽  
Significant Difference

Introduction: Inflammatory Breast Cancer (IBC) is a rare and very aggressive breast cancer with poor prognosis. The prevalence is different from a country to another. In Tunisia, it is about 5 to 7% of breast cancer. The aim of this study is to describe the epidemiological and histopathological features of patients with inflammatory breast cancer and to evaluate the treatment response according to the molecular subtypes. Methods: This retrospective review identified 31 patients with no metastatic IBC treated in our radiotherapy department between December 2019 and November 2020. IBC was confirmed using the clinical criteria. Baseline clinic-pathological and treatment information was retrieved from medical records. Statistical analysis was performed with IBM SPSS V.20. Results: Median age was 51.3 years [27-68]. 48% of tumors were grade 3. The average tumor size was 36mm [10-90]. The histological type was ductal carcinoma in 97%. Vascular invasion was noted in 24 patients (77%). Thirty patients were classified as stage IIIB and one patient was IIIC. 74% were hormone receptor positive and 45% were HER2 positive. Luminal B was the predominant subtype (52%) followed by Her2 positive (32%), Luminal A (23%), and triple negative (3%) All patients had chemotherapy: neoadjuvant for 26 patients (84%) and adjuvant for 5 patients (16%). Nine patients (29%) had tumor pathological complete response (pCR). Partial response was observed in 18 patients (58%). Lymph node pCR was noted in 16% of cases (n=5). Endocrine therapy and trastuzumab were given to 76% and 45% of patients, respectively. The influence of the molecular subtype was not statistically significant on the response to neoadjuvant treatment. The highest rate of pCR were 43% for Her2positive, then 27%, 21% and 9% for Luminal B, Luminal A and Triple negative, respectively (p=0.2). Conclusion: Our study showed a high percentage of hormone receptor and Her2+ (74% and 45% respectively) in IBC. Luminal B was the most frequent subtype. Anthracycline-based chemotherapy and trastuzumab improved the pCR rate: 44% for Her2positive. Triple negative showed poorer pCR than other breast cancer subtype without a significant difference. A larger study is warranted to confirm our findings.

scholarly journals Diffusion-Weighted Imaging of Different Breast Cancer Molecular Subtypes: A Systematic Review and Meta-Analysis

Breast Care ◽  
2021 ◽  
pp. 1-8
Author(s):  
Hans-Jonas Meyer ◽  
Andreas Wienke ◽  
Alexey Surov
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Diffusion Weighted Imaging ◽  
Triple Negative ◽  
Molecular Subtypes ◽  
Luminal A ◽  
Diagnose Breast Cancer ◽  
Luminal B ◽  
Diffusion Weighted ◽  
Adc Values

Background: Magnetic resonance imaging can be used to diagnose breast cancer (BC).Diffusion-weighted imaging (DWI) and the apparent diffusion coefficient (ADC) can be used to reflect tumor microstructure. Objectives: This analysis aimed to compare ADC values between molecular subtypes of BC based on a large sample of patients. Method: The MEDLINE library and Scopus database were screened for the associations between ADC and molecular subtypes of BC up to April 2020. The primary end point of the systematic review was the ADC value in different BC subtypes. Overall, 28 studies were included. Results: The included studies comprised a total of 2,990 tumors. Luminal A type was diagnosed in 865 cases (28.9%), luminal B in 899 (30.1%), human epidermal growth factor receptor (Her2)-enriched in 597 (20.0%), and triple-negative in 629 (21.0%). The mean ADC values of the subtypes were as follows: luminal A: 0.99 × 10–3 mm2/s (95% CI 0.94–1.04), luminal B: 0.97 × 10–3 mm2/s (95% CI 0.89–1.05), Her2-enriched: 1.02 × 10–3 mm2/s (95% CI 0.95–1.08), and triple-negative: 0.99 × 10–3 mm2/s (95% CI 0.91–1.07). Conclusions: ADC values cannot be used to discriminate between molecular subtypes of BC.

Trends in breast cancer mortality according to molecular subtypes: A population-based study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 572-572
Author(s):  
Yunan Han ◽  
Shuai Xu ◽  
Graham A. Colditz ◽  
Adetunji T. Toriola
Keyword(s):  
Breast Cancer ◽  
Cancer Mortality ◽  
Triple Negative ◽  
Molecular Subtypes ◽  
Breast Cancer Mortality ◽  
Treatment Strategies ◽  
Luminal A ◽  
Her2 Positive ◽  
Mortality Trends ◽  
Luminal B

572 Background: Breast cancer is the second leading cause of cancer death in U.S. women. On the molecular level, breast cancer is a heterogeneous disease. Heterogeneous expressions of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) are etiologically and clinically meaningful, as they map to distinct risk factors and different treatment strategies. Although breast cancer mortality has been declining since 1990, little is known about mortality trends according to molecular subtypes at the population level. Methods: We examined the incidence-based mortality rates and trends among women who were diagnosed with invasive breast cancer from 2010 through 2017 using the Surveillance, Epidemiology, and End Results (SEER) database. We defined incidence-based mortality using a moving 5-year calendar period starting in 2014. We further assessed mortality according to breast cancer molecular subtypes: luminal A (ER and/or PR positive, HER2 negative), luminal B (ER and/or PR positive, HER2 positive), HER2-enriched (HER2 over-expressed or amplified, ER and PR negative) and triple-negative (ER and PR negative, HER2 negative) tumors. We calculated annual percent changes (APC) in incidence-based mortality using joinpoint regression models. Results: Overall, incidence-based mortality for breast cancer significantly decreased by 1.5% annually from 2014 through 2017 (APC, -1.5%; 95% coefficient interval [CI], -2.3% to -0.7%; p<0.001). Incidence-based mortality decreased annually by 2.0% for luminal A breast cancer (APC, -2.0%; 95% CI, -3.7% to -0.3%; p<0.001), 2.1% for luminal B breast cancer (APC, -2.1%; 95% CI, -5.4% to 1.4%; p=0.1), 1.1% for triple-negative breast cancer (TNBC) (APC, -1.1%; 95% CI, -2.1% to -0.0%; p<0.001). However, incidence-based mortality for HER2-enriched breast cancer increased 2.3% annually during the study period (APC, 2.3%; 95% CI, -2.4% to 7.2%; p=0.2). Conclusions: Between 2014 and 2017, incidence-based mortality for luminal A, luminal B, and TNBC decreased among U.S. women, with a larger decrease observed for luminal tumors. However, incidence-based mortality for HER2-enriched breast cancer increased. The favorable incidence-based mortality trends for luminal tumors and TNBC are likely due to the continuing improvement in treatments and early detection. The increasing trend of incidence-based mortality for HER2-enriched breast cancer constitutes a priority for cancer control activities and further research.

scholarly journals Analysis of prolactin receptor expression in breast cancer subtypes

2020 ◽  
Vol 66 (1) ◽  
pp. 89-94
Author(s):  
T.S. Kalinina ◽  
V.V. Kononchuk ◽  
S.V. Sidorov ◽  
L.F. Gulyaeva
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Prolactin Receptor ◽  
Mrna Level ◽  
Receptor Expression ◽  
Mrna Levels ◽  
Luminal A ◽  
Her2 Positive ◽  
Tissue Samples ◽  
Luminal B

Breast cancer (BC) is the most common cancer among women. It is known that the prolactin receptor (PRLR) may play a role in breast carcinogenesis, but the available data are often contradictory. To get a more complete picture of the relationship between the receptor and mammary gland carcinogenesis, we examined the association between changes in PRLR expression level and tumor subtype (and its main characteristics). To do this, using real-time PCR, we evaluated the level of PRLR mRNA in BC tissue samples and untransformed adjoining tissue samples (89 pairs). Since the androgen receptor (AR) has begun to be seen as a prognostic marker in breast cancer, we also evaluated the association between mRNA levels of AR and PRLR. We found a significant increase in PRLR expression in luminal subtypes; the highest level of PRLR mRNA was detected in luminal A subtype. In HER2-positive ER-, PR-negative BC, the PRLR mRNA level decreases in tumor tissues compared with untransformed tissues. High PRLR expression is also associated with smaller tumor size in luminal B HER2-negative subtype. In ER-, PR-negative tumors, PRLR expression is associated with AR expression: PRLR mRNA level is increased when AR mRNA level is reduced by more than 8 times in triple-negative tumors; in contrast, in HER2-positive subtype it decreases more significantly when AR expression is reduced by more than 3 times. A tendency towards an increase in PRLR expression with an increase in the AR mRNA level was also discovered in luminal subtypes. The level of PRLR expression depends on the age of patients. In luminal A, PRLR expression is higher in patients under 65 years. In contrast, in luminal B HER2-negative and triple-negative BC, reduced PRLR expression was observed in patients under the age of 40 years and under the age of 50 years, respectively. In this group of patients under the age of 40 years with luminal B HER2-negative BC, ER expression was also reduced (0-4 score according to the IHC assay). Thus, PRLR probably plays a different role in the development and progression of BC: in luminal A and luminal B HER2-positive subtypes PRLR may act as an oncogen, and in luminal B HER2-negative and ER-, PR-negative subtypes can play a tumor suppressor role.

Breast cancer in Angola, molecular subtypes: The first preliminary study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e13075-e13075
Author(s):  
Lúcio Lara Santos ◽  
Fernando Miguel ◽  
Lygia Vieira Lopes ◽  
Julio Oliveira ◽  
Eduardo Ferreira ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Molecular Subtypes ◽  
Molecular Subtype ◽  
Locally Advanced ◽  
Luminal A ◽  
Her2 Positive ◽  
Luminal B ◽  
Therapeutic Decisions ◽  
Ihc Markers

e13075 Background: Women in sub-Saharan African countries, as Angola, are experiencing an increasing burden of aggressive breast cancer. Breast cancer molecular subtypes may enable more accurate diagnoses and support therapeutic decisions, however several studies have suggested that African breast cancers are predominantly hormone receptor poor. We conduct a study, to correlate the clinical pathological profiles and molecular subtypes, according its surrogate immunohistochemistry (IHC) markers, of breast cancer in Luanda, Angola. Methods: From Jan. 2011 to Dec. 30, 2014, 179 consecutive cases of microscopically confirmed invasive breast carcinoma that were evaluable for histology and IHC (ER, PR, HER2, and Ki-67) were classified. However, 21.8% (n = 39) of cases were poorly preserved, therefore it was only possible to study IHC in 140 cases. Results: All patients were female, the median age was 47 years (24-84 years). Invasive ductal carcinoma was the most common type, 91.4% (n = 128), grade 2 (moderately differentiated) was prevalent, 67.1%. Most of the tumours were locally advanced, stage III 65% (n = 91) and stage IV 3.6% (n = 5). In 140 cases studied, 53.2% (n = 74 ) of malignancies were hormone receptors positive, whence 25.7% were luminal A like, 19.3% luminal B like/ HER2 negative, 7.9% luminal B like/HER2 positive, 15.7% HER2 positive and 31,4% were triple-negative. Conclusions: Woman with breast cancer in Luanda-Angola were caracterized by advance stage and younger age at diagnosis of disease. The two predominant molecular subtypes are triple negative and luminal A like. Therefore, determining the molecular subtype using surrogate IHC markers has important treatment and prognostic implications for Angola women with breast cancer.

scholarly journals Diffusion Weighted Imaging of Different Breast Cancer Molecular Subtypes. A Systematic Review and Meta Analysis.

2020 ◽  
Author(s):  
Hans-Jonas Meyer ◽  
Andreas Wienke ◽  
Alexey Surov
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Diffusion Weighted Imaging ◽  
Triple Negative ◽  
Molecular Subtypes ◽  
Luminal A ◽  
Adc Value ◽  
Luminal B ◽  
Adc Values ◽  
Her 2

Abstract Background: Magnetic resonance imaging can be used to diagnose breast cancer (BC)s. Diffusion weighted imaging and the apparent diffusion coefficient (ADC) can be used to reflect tumor microstructure. The present analysis sought to compare ADC values between molecular subtypes of BC based upon a large patient sample.Methods: MEDLINE library and SCOPUS databases were screened for the associations between ADC and molecular suptype of BC to April 2020. Primary endpoint of the systematic review was the ADC value in different BC. Overall, 28 studies were suitable for the analysis and included into the present study.Results: The included studies comprised a total of 2990 tumors. Luminal A type was diagnosed in 865 cases (28.9%), Luminal B in 899 cases (30.1%), Her-2 enriched in 597 cases (20.0%) and triple negative in 629 cases (21.0%). The mean ADC value of the Luminal A type was 0.99 × 10− 3 mm2/s [95% CI 0.94-1.04], of the Luminal B type was 0.99 × 10− 3 mm2/s [95% CI 0.89-1.05], of Her 2-enriched type was 1.02 × 10− 3 mm2/s [95% CI 0.95-1.08] and of the triple negative type was 0.99 × 10− 3 mm2/s [95% CI 0.91-1.07].Conclusions: ADC values cannot be used to discriminate between molecular subtypes of BC.

scholarly journals BRCA1 and TOP2A gene amplification and protein expression in four molecular subtypes of breast cancer

2013 ◽  
Vol 65 (2) ◽  
pp. 511-518 ◽  
Author(s):  
Olivera Mitrovic ◽  
Mileva Micic ◽  
V. Cokic ◽  
Vesna Koko ◽  
Dragoslava Djikic ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Expression ◽  
Significant Positive Correlation ◽  
Triple Negative ◽  
Molecular Subtypes ◽  
Protein Overexpression ◽  
Brca1 Protein ◽  
Luminal B ◽  
Top2a Gene ◽  
Top2a Amplification

We studied TOP2A amplification (using FISH methods), and TOP2A and BRCA1 protein overexpression (immunohistochemistry) in four molecular subtypes of breast cancer. Of 53 patients, 32 showed TOP2A and 38 showed BRCA1 overexpression. The highest percentage of TOP2A amplification (47.8%) and deletion (13%) was detected in Luminal B subtypes. Of 11 Luminal B tumors with TOP2A amplification, 9 (81.8%) overexpressed TOP2A. BRCA1 protein overexpression showed significant positive correlation with TOP2A protein expression. BRCA1 and TOP2A proteins exhibited similar patterns of expression in Luminal B and triple-negative breast cancer, suggesting the same prognosis in those patients.

scholarly journals Radiomic signatures with contrast-enhanced magnetic resonance imaging for the assessment of breast cancer receptor status and molecular subtypes: initial results

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Doris Leithner ◽  
Joao V. Horvat ◽  
Maria Adele Marino ◽  
Blanca Bernard-Davila ◽  
Maxine S. Jochelson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Molecular Subtypes ◽  
Training Dataset ◽  
Validation Dataset ◽  
Resonance Imaging ◽  
Luminal A ◽  
Receptor Status ◽  
Luminal B ◽  
Contrast Enhanced

Abstract Background To evaluate the diagnostic performance of radiomic signatures extracted from contrast-enhanced magnetic resonance imaging (CE-MRI) for the assessment of breast cancer receptor status and molecular subtypes. Methods One hundred and forty-three patients with biopsy-proven breast cancer who underwent CE-MRI at 3 T were included in this IRB-approved HIPAA-compliant retrospective study. The training dataset comprised 91 patients (luminal A, n = 49; luminal B, n = 8; HER2-enriched, n = 11; triple negative, n = 23), while the validation dataset comprised 52 patients from a second institution (luminal A, n = 17; luminal B, n = 17; triple negative, n = 18). Radiomic analysis of manually segmented tumors included calculation of features derived from the first-order histogram (HIS), co-occurrence matrix (COM), run-length matrix (RLM), absolute gradient (GRA), autoregressive model (ARM), discrete Haar wavelet transform (WAV), and lesion geometry (GEO). Fisher, probability of error and average correlation (POE + ACC), and mutual information coefficients were used for feature selection. Linear discriminant analysis followed by k-nearest neighbor classification (with leave-one-out cross-validation) was used for pairwise radiomic-based separation of receptor status and molecular subtypes. Histopathology served as the standard of reference. Results In the training dataset, radiomic signatures yielded the following accuracies > 80%: luminal B vs. luminal A, 84.2% (mainly based on COM features); luminal B vs. triple negative, 83.9% (mainly based on GEO features); luminal B vs. all others, 89% (mainly based on COM features); and HER2-enriched vs. all others, 81.3% (mainly based on COM features). Radiomic signatures were successfully validated in the separate validation dataset for luminal A vs. luminal B (79.4%) and luminal B vs. triple negative (77.1%). Conclusions In this preliminary study, radiomic signatures with CE-MRI enable the assessment of breast cancer receptor status and molecular subtypes with high diagnostic accuracy. These results need to be confirmed in future larger studies.

scholarly journals BRCA1/2 pathogenic variants in triple-negative versus luminal-like breast cancers: genotype–phenotype correlation in a cohort of 531 patients

2020 ◽  
Vol 12 ◽  
pp. 175883592097532
Author(s):  
Lorena Incorvaia ◽  
Daniele Fanale ◽  
Marco Bono ◽  
Valentina Calò ◽  
Alessia Fiorino ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Molecular Subtypes ◽  
University Hospital ◽  
Sequencing Analysis ◽  
Breast Cancers ◽  
Luminal B ◽  
Pathogenic Variants ◽  
Mutational Status ◽  
Phenotypic Features

Background: Several available data suggest the association between specific molecular subtypes and BRCA1/2 mutational status. Previous investigations showed the association between BRCA1/2 pathogenic variants (PVs) in specific genomic regions and phenotypic variations of cancer relative risk, while the role of PV type and location in determining the breast cancer (BC) phenotypic features remains still unclear. The aim of this research was to describe the germline BRCA1/2 PVs in triple-negative breast cancer (TNBC) versus luminal-like BC and their potential leverage on BC phenotype. Patients & methods: We retrospectively collected and analyzed all clinical information of 531 patients with BC genetically tested for germline BRCA1/2 PVs by Next-Generation Sequencing analysis at University Hospital Policlinico “P. Giaccone” of Palermo (Sicily) from January 2016 to February 2020. Results: Our results corroborate the evidence that BRCA1-related tumors often have a profile which resembles the TNBC subtype, whereas BRCA2-associated tumors have a profile that resembles luminal-like BC, especially the Luminal B subtype. Interestingly, our findings suggest that the PVs identified in TNBC were not largely overlapping with those in luminal-like tumors. Differences in the frequency of two PVs potentially associated with different molecular tumor subtypes were observed. BRCA1-633delC was detected with relatively higher prevalence in patients with TNBC, whereas BRCA2-1466delT was found mainly in Luminal B tumors, but in no TNBC patient. Conclusion: Future studies examining the type and location of BRCA1/2 PVs within different molecular subtypes are required to verify our hypothesis and could provide an interesting insight into the complex topic of genotype–phenotype correlations. Additionally, a more in-depth understanding of the potential correlations between BRCA PVs and clinical and phenotypic features of hereditary BC syndrome patients could be the key to develop better strategies of prevention and surveillance in BRCA-positive carriers without disease.

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