scholarly journals Mutations in tumor suppressor genes and their relationship with phenotypic features of breast cancer in young age women

2018 ◽  
Vol 16 (3) ◽  
pp. 62-71
Author(s):  
Lyudmila A. Gordeeva ◽  
Ilija E. Lojko ◽  
Elena N. Voronina ◽  
Ekaterina E. Kutonova ◽  
Elena G. Polenok ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Suppressor Genes ◽  
Sporadic Breast Cancer ◽  
Triple Negative ◽  
Young Age ◽  
Founder Mutations ◽  
Luminal A ◽  
Chek2 1100Delc ◽  
Melting Analysis ◽  
Phenotypic Features

Background. Breast cancer (BC) is the most common oncological disease in women in the world. The aim of study is to investigate the frequencies of mutations in BRCA1 5382insC (rs80357906), CHEK2 1100delC (rs555607708) and BLM c.1642 C>T (rs200389141) genes and their relationship with the phenotypic features of BC in 104 young age women. Materials and methods. We studied 104 young age women with breast cancer. Typing of mutations BRCA1 5382insC, CHEK2 1100delC and BLM c.1642 C>T genes were performed by real-time PCR followed by melting analysis. Results. The BRCA1 5382insC mutation was detected in 9.6% of BC patients. The BRCA1 5382insC mutation was correlated with the lack of expression of estrogen receptors (χ2 = 18.48, d(f) = 1, p < 0.0001), the HER2/neo tumor receptor (χ2 = 5.61, d(f) = 1, p < 0.02). The BRCA1 5382insC mutation was more often in the “triple negative” BC (χ2 = 17.42, d(f) = 3, p < 0.001). Luminal A subtype of disease was observed the predominantly in non-carriers of the mutation BRCA1 5382insC (sporadic breast cancer). The founder mutations in the CHEK2 1100delC and BLM c.1642 C>T genes were absent in young age women with BC. Conclusion. Our results confirm the high significance of detecting the BRCA1 rs80357906 mutation in young age women with BC for optimization of treatment tactic and for early diagnosis of BC.

Stage, biology, and age.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11512-e11512
Author(s):  
Hee Jeong Kim ◽  
Beom Seok Ko ◽  
Jong Han Yu ◽  
jong Won Lee ◽  
Byung Ho Sohn ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Triple Negative ◽  
Medical Center ◽  
Intrinsic Subtype ◽  
Young Age ◽  
Tnm Stage ◽  
Intrinsic Subtypes ◽  
Luminal A ◽  
Survival Difference

e11512 Background: Breast cancer subtypes are prognostic and predictive for patients. In this study, prognostic value of TNM stage, intrinsic subtype, and age were compared. Methods: We analyzed results from 7,626 breast cancer patients registered on the Asan medical center database between 1999 and 2009. We compared survival according to the TNM stage, intrinsic subtype using ER, PR, Her2- immunohistochemical staining, and age. Results: Luminal A subtype showed the best survival rates while triple negative subtype showed the worst survival rate amongst intrinsic subtypes. Survival analysis showed that Stage I triple negative breast cancer showed better survival compared to Stage III Luminal A subtype breast cancer (89.0% vs 76.6% P<0.001). Survival differences between intrinsic subtypes were more significant in lymph node positive breast cancer compared to lymph node negative breast cancer. Age did not affect survival between stages and intrinsic subtypes except for the young age subgroup (≤35), for whom there was no survival difference amongst intrinsic subtypes. Conclusions: Staging of breast cancer showed a more direct correlation to survival than known prognosis for intrinsic subtypes, as advanced, good prognostic intrinsic subtype breast cancer had worse survival than early, worse prognostic intrinsic subtype breast cancer. However for the young age group (≤35), the survival of all intrinsic subtypes were similar.

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.

scholarly journals The Roles of DNA Demethylases in Triple-Negative Breast Cancer

2021 ◽  
Vol 14 (7) ◽  
pp. 628
Author(s):  
Shoghag Panjarian ◽  
Jean-Pierre J. Issa
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Tumor Suppressor Genes ◽  
Hormone Receptors ◽  
Triple Negative ◽  
Breast Cancers ◽  
Therapeutic Implications ◽  
High Propensity ◽  
Dna Methylation Profile

Triple-negative breast cancers (TNBCs) are very heterogenous, molecularly diverse, and are characterized by a high propensity to relapse or metastasize. Clinically, TNBC remains a diagnosis of exclusion by the lack of hormone receptors (Estrogen Receptor (ER) and Progesterone Receptor (PR)) as well as the absence of overexpression and/or amplification of HER2. DNA methylation plays an important role in breast cancer carcinogenesis and TNBCs have a distinct DNA methylation profile characterized by marked hypomethylation and lower gains of methylations compared to all other subtypes. DNA methylation is regulated by the balance of DNA methylases (DNMTs) and DNA demethylases (TETs). Here, we review the roles of TETs as context-dependent tumor-suppressor genes and/or oncogenes in solid tumors, and we discuss the current understandings of the oncogenic role of TET1 and its therapeutic implications in TNBCs.

scholarly journals CD44 Targeted Nanomaterials for Treatment of Triple-Negative Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 898
Author(s):  
Ghazal Nabil ◽  
Rami Alzhrani ◽  
Hashem Alsaab ◽  
Mohammed Atef ◽  
Samaresh Sau ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
In Vivo Studies ◽  
High Dose ◽  
Luminal A ◽  
Combination Strategy ◽  
Ongoing Research

Identified as the second leading cause of cancer-related deaths among American women after lung cancer, breast cancer of all types has been the focus of numerous research studies. Even though triple-negative breast cancer (TNBC) represents 15–20% of the number of breast cancer cases worldwide, its existing therapeutic options are fairly limited. Due to the pivotal role of the presence/absence of specific receptors to luminal A, luminal B, HER-2+, and TNBC in the molecular classification of breast cancer, the lack of these receptors has accounted for the aforementioned limitation. Thereupon, in an attempt to participate in the ongoing research endeavors to overcome such a limitation, the conducted study adopts a combination strategy as a therapeutic paradigm for TNBC, which has proven notable results with respect to both: improving patient outcomes and survivability rates. The study hinges upon an investigation of a promising NPs platform for CD44 mediated theranostic that can be combined with JAK/STAT inhibitors for the treatment of TNBC. The ability of momelotinib (MMB), which is a JAK/STAT inhibitor, to sensitize the TNBC to apoptosis inducer (CFM-4.16) has been evaluated in MDA-MB-231 and MDA-MB-468. MMB + CFM-4.16 combination with a combination index (CI) ≤0.5, has been selected for in vitro and in vivo studies. MMB has been combined with CD44 directed polymeric nanoparticles (PNPs) loaded with CFM-4.16, namely CD44-T-PNPs, which selectively delivered the payload to CD44 overexpressing TNBC with a significant decrease in cell viability associated with a high dose reduction index (DRI). The mechanism underlying their synergism is based on the simultaneous downregulation of P-STAT3 and the up-regulation of CARP-1, which has induced ROS-dependent apoptosis leading to caspase 3/7 elevation, cell shrinkage, DNA damage, and suppressed migration. CD44-T-PNPs showed a remarkable cellular internalization, demonstrated by uptake of a Rhodamine B dye in vitro and S0456 (NIR dye) in vivo. S0456 was conjugated to PNPs to form CD44-T-PNPs/S0456 that simultaneously delivered CFM-4.16 and S0456 parenterally with selective tumor targeting, prolonged circulation, minimized off-target distribution.

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.

Geographical disparities of incidence and prevalence of triple-negative breast cancers: Multistate study data analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12599-e12599
Author(s):  
Hyein Jeon ◽  
Myeong Lee ◽  
Mohammed Jaloudi
Keyword(s):  
Breast Cancer ◽  
Black Women ◽  
Significant Relationship ◽  
White Women ◽  
Triple Negative ◽  
The State ◽  
Luminal A ◽  
Black Females ◽  
Black And White ◽  
State Effect

e12599 Background: Higher prevalence of triple negative breast cancer (TNBC) in black women with associated poor outcomes due to various disparities is well documented within a single state. We examine multiple states to better understand the state effect on such differences in incidence and prevalence of TNBC in black women. Methods: Female patients of ages 19 years old and above with breast cancer from the Surveillance, Epidemiology and End Results (SEER) Program across 13 states (608 counties) from 2015 (n = 66,444) and 2016 (n = 66,122) were examined. The relationships between the proportion of black and white women and the rate of patients with different tumor subtypes (luminal A, luminal B, HR-HER2+, and triple negative) were examined at the county level using ordinary least-square regression models. In parallel, due to consideration of various state-specific healthcare policies, socio-cultural norms, and socio-economic disparities, multi-level regression models were applied to examine the nested, random effect of each state on TNBC prevalence in each county. Bonferroni correction was applied to reduce the Type I error caused by repeated use of the same variables in multiple tests. Results: The baseline breast cancer rates between black and white women were similar in the population (0.171% for black and 0.168% for white). Consistent to previous studies, we demonstrate a significant positive correlation (p < 0.001) in TNBC in black females in both years. Surprisingly, when accounted for the random effects on states, 38.2% (2015) and 34.3% (2016) increase in incidence of TNBC in black females were seen, suggestive of state-specific disparity affecting race-specific health. In 2015, other subtypes of breast cancer in both black and white females did not result in significant relationship. Interestingly, in 2016, there was a significant relationship seen between the TNBC rate in white females and the white female population rate only after adjusting for the state effect (p = 0.026). This indicates the impact of non-biological factors such as state-wide health policies. Additionally, HR-HER2+ black females had a significant relationship against respective population rate only after adjusting for the state effect as well (p = 0.0394). For luminal A white females, a 15% decrease in incidence was seen after adjusting for state effect (p = 0.0424). Conclusions: This is the first known across-state examination of breast cancer subtypes by race with random effects on state. This study shows the role of state-specific factors affecting incidence in black and white females and potentially indicates the importance of state-level management for breast cancer on health disparities in addition to race-driven effects. Further studies are needed to elucidate comparable differences between states affecting the rates of various subtypes of breast cancer and thus health outcomes.

scholarly journals Low KIBRA Expression Is Associated with Poor Prognosis in Patients with Triple-Negative Breast Cancer

Medicina ◽  
2021 ◽  
Vol 57 (8) ◽  
pp. 837
Author(s):  
So-Woon Kim ◽  
Jinah Chu ◽  
Sung-Im Do ◽  
Kiyong Na
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Poor Prognosis ◽  
Triple Negative ◽  
Histological Grade ◽  
Growth Factor Receptor ◽  
Hippo Signaling ◽  
Luminal A ◽  
Luminal B ◽  
Epidermal Growth

Background and Objectives: Kidney and brain protein (KIBRA) is a protein encoded by the WW and C2 domain containing 1 (WWC1) gene and is involved in the Hippo signaling pathway. Recent studies have revealed the prognostic value of KIBRA expression; however, its role in breast cancer remains unclear. The aim of this study was to examine KIBRA expression in relation to the clinical and pathological characteristics of patients with breast cancer and to disease outcomes. Materials and Methods: We analyzed the expression of KIBRA and its correlation with event-free survival (EFS) outcomes in resected samples from 486 patients with breast cancer. Results: KIBRA expression was significantly different among the molecular subgroups (low KIBRA expression: luminal A, 46.7% versus 50.0%, p = 0.641; luminal B, 32.7% versus 71.7%, p < 0.001; human epidermal growth factor receptor 2 (HER2)-enriched, 64.9% versus 45.5%. p = 0.001; triple-negative, 73.6% versus 43.8%, p < 0.001). Low KIBRA expression was also associated with high nuclear grade (60.4% versus 37.8%, p < 0.001), high histologic grade (58.7% versus 37.0%, p < 0.001), and estrogen receptor (ER) negativity (54.2% versus 23.6%, p < 0.001). Low KIBRA expression was significantly associated with poor EFS (p = 0.041; hazard ratio (HR) 1.658; 95% confidence interval (CI), 1.015–2.709). Low KIBRA expression was an independent indicator of poor prognosis (p = 0.001; HR = 3.952; 95% CI = 1.542–10.133) in triple-negative breast cancer (TNBC). Conclusion: Low KIBRA expression was associated with higher histological grade, ER negativity and poor EFS of breast cancer. In particular, our data highlight KIBRA expression status as a potential prognostic marker for TNBC.

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.

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