Pathological Features Of Breast Cancer Research Articles

Relação entre a exposição ocupacional a Radiação Ionizante em Trabalhadores da Saúde e o desenvolvimento de Cancro de Mama

Introduction Every year more than 2.3 million cases of breast cancer are registered, making it the most common type of cancer among adults. The association between breast cancer and occupational factors is an issue that has been studied in the literature since the beginning of the 18th century. Technological developments have allowed a more in-depth study of the relationship between breast cancer and occupational factors such as exposure to chemicals, pesticides, metals and also sources of exposure to ionising and non-ionising radiation.The aim of the present literature review is to complete an update on the scientific knowledge about the relationship between occupational exposure to ionising radiation in healthcare workers and the development of breast cancer. Methodology A research was carried using Medline with the PubMed search engine and Elsevier with the Science Direct search engine. The search words used were a combination of breast cancer, occupational exposure, ionizing radiation and healthcare workers. A research was also carried out in the Revista Portuguesa de Saúde Ocupacional, using the terms “Breast Cancer” and “Ionizing Radiation”. Discussion/Conclusions Current literature is not unanimous about the specific clinical and pathological features of breast cancer possibly linked to occupational settings. Healthcare professionals such as radiology technicians, nurses, orthopaedic surgeons and interventional cardiologists are especially vulnerable to this type of exposure, particularly to ionising radiation. However, some studies have pointed to a difficulty in establishing a causal relationship between these factors due to the number of variables involved, such as the duration and intensity of exposure and the influence of other risk factors. Changes in equipment, procedures and protective measures have resulted in lower doses in recent years, which means that the risk of breast cancer is low at current levels of occupational exposure to ionizing radiation. Keywords: breast cancer, occupational exposure, ionizing radiation, healthcare workers, occupational medicine and occupational safety.

EXPRESSION PROFILE OF miR-145, -182, -21, -27a, -29b, and -34a IN BREAST CANCER PATIENTS OF YOUNG AGE.

Breast cancer (BC) in young women remains a significant public health concern. While progress has been made in understanding the etiology, diagnosis, and treatment of BC in this population, challenges persist. The identification and utilization of prognostic biomarkers offer valuable tools for tailoring treatment strategies and improving outcomes for BC patients. To evaluate the relationship between the expression of tumor-associated microRNAs and the clinical and pathological features of BC in young patients. The work is based on the results of the examination and treatment of 50 women younger than 45 years with stage I-II BC. miR-145, -182, -21, -27a, -29b, and -34a expression in tumor samples was analyzed by the real-time reverse transcription polymerase chain reaction. Higher expression of miR-182, -21, and -29b and lower levels of miR-27a were associated with tumor stage in young BC patients. Patients without lymph node metastases (N0) had significantly higher levels of miR-182, -27a, and -34a and lower levels of miR-29b compared to N1 cases (p < 0.05). Expression of miR-145, -182, -21, -27a, and -29b was associated with molecular BC subtypes. Obtained results show that a high malignancy degree of BC in young women is associated with an increase in the miR-182, -21, -29b, and -34a expressions and a decrease in the miR-27a level in the tumor tissue, which indicates the prospects of the use of them for predicting the aggressiveness of the disease.

RAB10 promotes breast cancer proliferation migration and invasion predicting a poor prognosis for breast cancer

RAB10, a member of the small GTPase family, has complex biological functions, but its role in breast cancer (BC) remains unclear. The aim of this study was to investigate the relationship between RAB10's role in BC, its biological functions, and BC prognosis. An online database was used to analyze the correlation between differential expression of RAB10 in BC and prognosis. The results of immunohistochemical assays in clinical cohorts were combined with the database analysis. The chi-square test and COX regression were employed to analyze the correlation between RAB10 and pathological features of BC. MTT, Transwell, and wound healing assays were conducted to detect BC cell proliferation, invasion, and metastatic ability. Bioinformatics techniques were employed to explore the correlation between RAB10 and BC tumor immune cell infiltration, and to speculate the biological function of RAB10 in BC and related signaling pathways. Our findings suggest that RAB10 expression is elevated in BC and is associated with HER2 status, indicating a poor prognosis for BC patients. RAB10 can promote the proliferation, migration, and invasion ability of BC cells in vitro. RAB10 is also associated with BC immune cell infiltration and interacts with multiple signaling pathways. RAB10 is a potential biomarker or molecular target for BC.

The value of multimodal magnetic resonance imaging in breast cancer and its correlation with pathological features and prognosis.

This study aimed to explore the diagnostic value of multimodal magnetic resonance imaging (MRI) in breast cancer (BC) and its correlation with pathological features of the disease. Clinical data of 85 BC patients (malignant group) and 85 patients with benign breast diseases (benign group), admitted to 3201 Hospital of Xi'an Jiaotong University Health Science Center from May 2020 to May 2022, were retrospectively collected. Both groups underwent multimodal MRI examinations. We compared the differences in multimodal MRI examination parameters between the groups, as well as between patients with different pathological characteristics and prognoses in the malignant group. The correlation between multimodal MRI examination parameters and pathological features of BC was analyzed. The apparent diffusion coefficient (ADC) of the malignant group was lower than that of the benign group, while the extravascular extracellular volume fraction (Ve), reaction rate constant (Kep), and volume transfer constant (Ktrans) of the malignant group were higher compared to the benign group (p<0.05). In the malignant group, patients with stage III+IV disease, lymph node metastases, and low differentiation had lower ADC values, and higher Ve, Ktrans, and Kep compared to patients with stage I+II disease, no lymph node metastasis, and medium to high differentiation (p<0.05). ADC value negatively correlated with the stage of the disease, lymph node metastases but positively correlated with the degree of differentiation (p<0.05). Ve, Ktrans, and Kep positively correlated with the stage of the disease and lymph node metastasis, and negatively correlated with the degree of differentiation (p<0.05). ADC value of patients with poor prognosis was lower, while Ve, Ktrans, and Kep were higher compared to patients with good prognosis (p<0.05). The Receiver operating characteristic (ROC) analysis showed that ADC, Ve, Ktrans, and Kep have certain predictive values for the poor prognosis of BC patients (p<0.05). Multimodal MRI examination detected obvious differences in the examination parameters of BC patients, and the increase or decrease in these parameters is closely correlated with the pathological characteristics and prognosis of the disease. Multimodal MRI examination can be used for pathological evaluation and prognosis prediction in BC patients.

Assessing pathological features of breast cancer via the multimodal information of multiphoton and Raman imaging

For unveiling the pathological evolution of breast cancer, nonlinear multiphoton microscopic (MPM) and confocal Raman microspectral imaging (CRMI) techniques were both utilized to address the structural and constitutional characteristics of healthy (H), ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC) tissues. MPM-based techniques, including two-photon excited fluorescence (TPEF) and second harmonic generation (SHG), visualized label-free and the fine structure of breast tissue. Meanwhile, CRMI not only presented the chemical images of investigated samples with the K-mean cluster analysis method (KCA), but also pictured the distribution of components in the scanned area through univariate imaging. MPM images illustrated that the cancer cells first arranged around the basement membrane of the duct, then proliferated to fill the lumens of the duct, and finally broke through the basement membrane to infiltrate into the stroma. Although the Raman imaging failed to visualize the cell structure with high resolution, it explained spectroscopically the gradual increase of nucleic acid and protein components inside the ducts as cancer cells proliferated, and displayed the distribution pattern of each biological component during the evolution of breast cancer. Thus, the combination of MPM and CRMI provided new insights into the on-site pathological diagnosis of malignant breast cancer, also ensured technical support for the development of multimodal optical imaging techniques for precise histopathological analysis.

Preliminary study on the significance of pathological characteristics analysis of breast cancer and detection of peripheral blood myeloid-derived suppressor cells in the evaluation of biological characteristics

ABSTRACT To explore the significance of the analysis of pathological characteristics of breast cancer and the detection of myeloid-derived suppressor cell (MDSC) levels in peripheral blood for the evaluation of biological characteristics. 138 breast cancer patients were enrolled as the research group, while 138 patients with benign breast diseases were included as the control group. All patients underwent pathological analysis and detection of peripheral blood MDSCs levels, progesterone receptor (PR), estrogen receptor (ER), human epidermal growth factor receptor 2 (HER-2), and proliferating cell nuclear antigen (Ki-67). A factorial study of stage I, II, and III breast cancer patients showed significant differences in clinicopathological characteristics, including age, tumor size, lymph node metastases, histological grading, Neuropsychiatric Inventory (NPI) score, pathological type, and family history (P < 0.05). The research group had higher levels of peripheral blood MDSCs and different cell surface markers compared to the control group (P<0.05). Positive expression of biological molecules in breast cancer, such as PR, ER, HER-2, and Ki-67, had significant differences based on lymph node metastasis and tumor size (P < 0.05). The quality of survival scores was higher in stages I and II compared to stage III (P < 0.05). Age, recurrence, metastasis, and other pathological characteristics of breast cancer have a direct impact on clinical outcomes and survival rates. Peripheral blood levels of MDSCs and other cell surface markers are significantly elevated, serving as a crucial benchmark for the subsequent evaluation of breast cancer progression.

Study of the Relationship betweenABO Blood Group Typesand Breast Cancer and Cervix Cancerin Khuzestan Province, Iran.

Background:Breast cancer and cervix cancer are the prevalent and deadly types of solid tumors around the world. According to the importance of cancer, it is necessary to understand predisposing factors that affect cancer risk. In this regard, previous studies suggest that blood types particularly ABO and Rh-Hr Blood-Group System could play roles in the risk and different features of cancers. In the present study, we aimed to evaluate the potential of ABO and Rh blood groups as risk factors for breast cancer and cervix cancer. Materials and Methods:A retrospective study included 109 and 14 patients diagnosed with breast cancer and cervix cancer, respectively with known ABO and Rh blood types, between 2018 and 2020 in Khuzestan province, Iran. For compression of ABO blood groups distribution between the cancer patients group and the healthy population, we used data from a large-scale study that report the distribution of ABO blood groups in 29,922 blood donors in Khuzestan province. Results:Based on obtained results the most frequent blood group is O followed by B, A, and AB in breast cancer and followed by A, B, and AB in cervix cancer. Results showed no significant association between ABO and Rh and the risk of breast and cervix cancer. Moreover, there is no relationship between blood types and clinic pathological features of breast cancer. Conclusion: Based on our data, ABO and in this regard, previous studies suggest that blood types particularly ABO and Rh-Hr Blood-Group System could play roles in the risk and different features of cancers. In the present study, we aimed to evaluate the potential of ABO and Rh blood groups as risk factors for breast cancer and cervix cancer do have not any association with the risk of breast and cervix cancer and their characteristics.

What Has Changed During the COVID-19 Pandemic? - The Effect on an Academic Breast Department in Portugal.

One year ago, Portugal entered its first lockdown because of the coronavirus disease-2019 (COVID-19) pandemic. The impact of this on delays in cancer diagnosis and treatment is a major concern, which may negatively affect the outcomes of these patients. This retrospective, single-center analysis compared the clinical and pathological characteristics of breast cancer (BC) patients referred to a medical oncology first appointment between March 2020 and 2021, with the same period in the previous year. Strikingly, there was a 40% reduction in the number of BC patients during lockdown. However, there was a statistically significant increase in the proportion of metastatic BC patients admitted for the first time for systemic therapy (13.6% vs. 28.9%, p = 0.003). Additionally, a statistically significant increase in the number of patients with bilateral early BC at diagnosis after March 2020 was found (7.2% vs. 1.9%, p = 0.043). These findings support international recommendations for an accelerated restoration of BC screening, to reduce incidence of advanced breast cancer at diagnosis and mitigate the expected impact of the COVID-19 pandemic on patients with cancer. Further work is needed to examine in detail the impact of measures to manage the COVID-19 pandemic on breast cancer outcomes.

Associations of Body Mass Index with Molecular Sub Types, Clinical and Pathological Characteristics of Breast Cancer in Bangladeshi Women

Obesity is a major health hazard not only for developed countries but also for Bangladesh and it is an established risk factor of breast cancer. In our country there is a scarcity of studies on the associations of BMI and different features of breast tumour. This study was aimed to evaluate the associations of BMI with molecular sub-types, clinical and pathological characteristics of breast cancer in Bangladeshi women. This cross sectional descriptive type of observational study was conducted in National Institute of Cancer Research and Hospital (NICRH), Mohakhali, Dhaka from September, 2019 to August, 2020. A total of 90 patients with breast cancer were selected purposively according to inclusion and exclusion criteria. An informed consent was sought from the patient to take part is this study. Detail history taking thorough physical examination was done along with relevant investigations. Data were collected by semi structured questionnaire and analysis was done with the help of Statistical Package for Social Science (SPSS), version 21.0. Mean age of the respondents was 41.17 years with a standard deviation of ±8.79 and a range of 24-65 years. Of all, ninety percent patients were housewives and 52.2% belonged to upper middle socio-economic class. About 66.7% patients were pre-menopausal and 33.3% were post-menopausal. The mean BMI of respondents was 25.89(±4.67) kg/m2 and among them 51.1% were obese, 23.3% were overweight and 20.0% had normal weight. No association between BMI and vii molecular subtypes of breast cancer were noted (p&gt;0.05). No association between BMI and hormone receptor status of breast cancer was found. Association with tumor size, axillary lymph nodes, tumor grade and lymphovascular space invasion were also not significant (p&gt;0.05). No association between BMI and molecular subtypes, clinical and pathological features of breast cancer were noted both in pre and post-menopausal groups. This study found no association between BMI and different features of tumor, which could be attributed to small sample size, absence of control and a single centered study. However, further extensive study is recommended.

Clinicopathological characteristics and prognosis in women with breast cancer affected by COVID 19.

e22517 Background: there are few reported series n women with breast cancer (BC) and COVID-19, a better prognosis has been observed, with a lower rate of hospitalization and mortality than other neoplasms. Methods: We conducted a restrospective, non-experimental, observational, single center, study with a sample of 69 patients with BC who had presented COVID-19, in the period between March 2020 to August 2021. Clinicopathological characteristics of patients with BC were compared between severe and non-severe covid 19 groups, as well as hospitalized and non-hospitalized patients. An analysis of possible risk factors associated with severe disease and hospitalization was performed. Results: 69 cases were reported, median age 52y, mean BMI 25.2, ECOG 0-1: 97%. Smoking history in 24%, diabetes and hypertension were the most frequent comorbidities. The most frequent histology was ductal carcinoma in 80.6%, 73.8% showed ER + and 69.3% PR +, HER2 was overexpressed in 9.2%. The early stages predominated, I 22 (31.3%), II 25 (37.3%), III in 12 (17.9%) and IV in 6 (9%). The most frequents symptoms of COVID-19 were fatigue 70.1%, fever 65.7%, cough 59.7%, headache 56.7%, hyposmia 47.8%, dysgeusia 38.8%. A total of 53 (76.8%) mild cases, 14 (20.3) severe cases and 2 (2.9%) critical cases were registered. The 89.9% (62 patients) were treated as an outpatient basis, while 7 (10.1%) required hospitalization. Active treatment (&lt; 45 days) at the time of COVID-19 was hormonal therapy 36 (50.7%), chemotherapy 11 (16.4%), anti-HER2 in 3 (4.5%), immunotherapy in 1.5%, targeted treatment in 4 (6.0%), surgery in 7 (10.4%) and radiotherapy in 1 (1.5%) patient. When comparing the severe and non-severe groups, as well as hospitalized versus non-hospitalized, we observed no difference between the clinicopathological characteristics. Then, we serch for possible risk factors, in wich, surgery in a period of less than 3 months increases the risk of severity OR 1,297 (95% CI 1,112-1,514), the risk of hospitalization increased in the triple negative subgroup OR 1,143 (95% CI, 1,035- 1,262), surgery less than 3 months OR 1,116 (1,014-1,229) and chemotherapy less than 45 days OR 1,217 (95% CI, 1,024-1,447). Conclusions: In patients with BC, the prevalence of severe or critical COVID-19 was 23% and the hospitalizacion rate 10%. No patient died from this infection. The clinical and pathological characteristics of BC do not appear to increase the risk of severe COVID-19 or the rate of hospitalization. Surgery performed in a period of less than 3 months is marginally associated with an increased risk of severe disease. Chemotherapy, targeted therapy, and immunotherapy do not modify the risk of severe disease; however, higher Ki 67, triple negative subgroup, surgery and chemotherapy showed a slight increase in risk of hospitalization.

Is Young Age an Independent Prognostic Factor in Carcinoma Breast? A Single-Institution Retrospective Comparative Study from South India.

Breast cancer is the most common cancer in women globally(1). It is usually a disease of old age. The incidence of breast cancer in females younger than 40years is as low as 0.5%. Disease in patients with age less than or equal to 40years at diagnosis is usually considered a young breast cancer(2). Occurrence of more adverse pathological features like triple negative and Her2 positive breast cancer as well as lacking reliable screening methods in young women leads to the poor prognosis in this group of patients(3). In the present study we aim to find the clinical and pathological characteristics of breast cancer in young women and their survival outcome for 5years comparing the same with those characteristics of the older patients. Patients with nonmetastatic carcinoma breast who had registered at Regional Cancer Centre, Trivandrum, during the year 2012 were selected for the study. Patient's details including the clinicopathological features, treatment details, oncologic outcomes including recurrence, and survival data until 31 July 2019 were collected from treatment files kept in the hospital and via telephonic interview. Kaplan-Meier method was employed for survival analysis. Survival comparison was done using the log-rank test. Cox proportional hazards regression analysis was done for assessing the risk. Out of 1611 curatively treated patients with carcinoma breast, 281 (17.44%) were young breast cancer (equal to or less than 40years). The median follow-up period was 82months. Median age of diagnosis was 51.3years. Young patients presented with larger tumour size, but nodal stage and composite stage, were not different. They had more TNBC status, 35% vs. 24%, p = 0.001. Young patient group had a drop in 5-year OS but statistically insignificant (75.9% vs. 82.5%, p = 0.179) and marginally significant drop in DFS (68.1% vs. 73.8%, p = 0.064). The proportion of young breast cancer is very high in the Indian population. Age is not an independent risk factor for worse prognosis. T and N stage, Her2nue status, and adequacy of nodal clearance are the most important independent risk factors deciding the 5-year OS.

Mutant Status of the P-53 Gene in Relation with microRNA, as an Unfavorable Marker in Breast Cancer, a Systematic Review

Breast cancer affects more than one million patients annually in the world and is a leading cause of mortality. Histological type, grade, tumor size, lymph node involvement, and estrogen receptor and HER-2 receptor status, all influence prognosis and the probability of response to systemic therapies. <strong>Purpose:</strong> Aim of this work was to emphasize possible links between alterations of the P-53 gene, together with its protein, in the pathological features of breast cancer, resistant to a conventional therapy. <strong>Method: </strong>New genetic technologies were investigated to promote a stronger anti-oncogene response, using both RNA-based p53 vaccines and the likelihood of response to specific oncological therapies. <strong>Results:</strong> Studies have shown that mutant P-53 gene had a strongly unfavorable prognostic factor for relapse-free survival and overall survival only in a triple-negative group in patients treated with adjuvant anthracycline-containing chemotherapy. The adjuvanted vaccine induced the type T1 cells helper response in most patients. However, the response has not yet been shown to be strong enough to be beneficial as monotherapy and most patients have had T-helper cells that have failed to produce effective cytokines to kill cancer cells. The results of these studies justified attempts to discover and apply the new vaccines to cancer patients using p53-derived peptides. <strong>Conclusions: </strong>Conditions of the mutant P-53 gene or deletion of 17p chromosome were an unfavorable prognostic factor for the survival of patients, treated with adjuvant chemotherapy, in the groups with triple-negative forms of BC.

The spectrum of HER2 expression in breast cancer: linking immunohistochemistry quantification with in situ hybridization assay.

We aimed to document the pathological characteristics of breast cancer (BC) cases with different scores of HER2 by immunohistochemistry (IHC), as well as to establish a relationship between HER2 expression and HER2 amplification by in situ hybridization (ISH). A cohort of 258 primary BC cases was evaluated for HER2 gene amplification with bright-field ISH. All HER2-negative and HER2-positive cases by IHC were concordant with the ISH classification. BC cases with score of 0 had lower average of HER2 copy number compared to cases with score of 1 + . HER2-equivocal cases by IHC had intermediate pathological characteristics between HER2-negative and HER2-positive cases. About 12% of HER2-equivocal cases were classified as ISH-positive. HER2-equivocal cases with HER2 gene amplification had proliferation index, HER2/CEP17 ratio, and average of HER2 copy number between HER2-equivocal cases without HER2 gene amplification and HER2-positive cases by IHC. Additionally, HER2-equivocal cases with HER2 amplification had score of 2 + in at least 50% of the total tumor area, with a proportion of ISH-positive cases increasing with the amount of score of 2 + present in the tumor. The quantification of score of 2 + in the tumor predicted the ISH classification with an AUC of 0.902. A logistic regression model using the same HER2 quantification and the nuclear score was able to increase the abovementioned prediction to an AUC of 0.929. As such, we were able to link HER2 quantification by IHC and morphological analysis with HER2 amplification by ISH.

Genetic Predisposition of Breast Cancer in the United Arab Emirates

This commentary refers to our published article, as highlighted in this article most common gene causing breast cancer in the population living in the United Arab Emirates is BRCA2 followed by BRCA1 [1]. This is the first publication discussing about clinical and pathological features of breast cancer in woman with a positive genetic mutation in the United Arab Emirates

Clinicopathological characteristics in women with breast cancer in extreme ages in Greece: A single centre experience

Abstract Introduction Breast cancer is the most common malignancy in Greek women. The highest incidence occurs in patients aged 40–70 years. However, the emergence of the disease in women under 40 and over 80 years old is a significant problem in everyday practice, because of the diagnostic and therapeutic challenges for these age groups. The objective of this study is to investigate clinicopathological characteristics of Greek women under 40 and over 80 diagnosed with breast cancer during 2019–2020 in a specialized Breast Cancer Surgical Centre, as well as the pathological characteristics of their disease and the therapeutic measures applied to these women. Aim of the study The aim of this study is to compare clinical and pathological characteristics of breast cancer in a group of Greek premenopausal women younger than 40 years of age with a group of elderly women older than 80 years old, who were treated in a surgical breast centre in Greece during the last two years. Patients and Methods During the last 2 years, 21 women under 40 and 22 women older than 80 were diagnosed with breast cancer in our Centre. Results Invasive ductal adenocarcinoma was the most frequent histological type for both Groups: Most younger women underwent surgery followed by chemotherapy, while the majority of older patients received hormonal therapy after surgery. Conclusions There were no statistically significant differences between women under 40 and women over 80 in the study sample regarding their clinicopathological characteristics. However, younger women underwent more therapeutic modalities (i.e.adjuvant treatments in addition to surgery) than older ones.

Clinical and Pathological Features of Breast Cancer in Systemic Sclerosis: Results from the Sclero-Breast Study.

Systemic Sclerosis (SSc) is a chronic disease associated with a 1.5-fold increase in cancer risk, including lung cancer, hematological malignancies, and breast cancer (BC). This is a retrospective study aiming to explore the clinical and pathological features of BC developed by SSc patients. A total of 54.5% of patients developed BC before SSc (median interval: 5 years), whereas 45.5% of patients developed BC after SSc (median delay: 8 years). A total of 93.1% of patients were diagnosed with an early stage tumor. Among invasive carcinomas, 70.8% presented with a low Mib1, 8.3% with a tubular histotype, and 42.8% with a Luminal A-like phenotype. A total of 66.6% of patients underwent breast-conserving surgery and 55.5% RT. A total of 40% of patients developed interstitial lung disease after RT and 20% diffuse cutaneous SSc. The cause of death of the six deceased patients was PAH. A significant association was observed between the use of immunosuppressive therapy and diffuse skin extension, negative ACA, positive Anti-Scl-70, and interstitial lung disease, but not BC status. SSc patients developed BC at a good prognosis, suggesting a de-escalation strategy of cancer therapies. In particular, ionizing radiation and chemotherapeuticals should be limited to higher-risk cases. Finally, proper screening is mandatory in order to allow for early cancer detection in SSc patients.

Clinical and pathological characteristics of breast cancer with resected brain metastasis.

1089 Background: Breast cancer brain metastasis (BCBM) has poor prognosis and limited therapeutic options. Studies have shown that BCBM may differ from their matched primary tumors in receptor subtypes and genomic characteristics. However, studies have been limited by the tissue availability of BCBM. Taking advantage of our institutional database of resected BCBM with matched primary breast samples, this study aimed to investigate the clinical and pathological characteristics of patients with resected BCBM. Methods: We performed retrospective chart review for all breast cancer patients who had resected BCBM samples at our institution over the last 20 years. Hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status of the primary breast and BCBM samples, location of BCBM, and extracranial metastases at time of BCBM diagnosis were categorized. Overall survival (OS) from time of BCBM diagnosis was calculated using the Kaplan-Meier method. Progression interval and receptor subtype switching from primary diagnosis to brain metastasis were computed and compared using Wilcoxon rank sum test and Fisher’s exact test, respectively. Results: Eighty-six patients were included in this study (median age at time of BCBM diagnosis 54.3 [range 28.3-84.0] years, median follow up 26.0 months). These included 47 HR+, 15 HER2+, 20 triple negative (TN), 4 unknown subtype breast samples, and 42 HR+, 18 HER2+, 17 TN and 9 unknown subtype brain samples. OS was significantly shorter in patients with TN compared to HR+ or HER2+ subtype, whether the TN status was in the primary breast tumor (median 20.5 vs 34.0 months, p = 0.04, thresholded at year 2) or in the brain metastasis (median 16.0 vs 34.0 months, p = 0.02, thresholded at year 2). No significant difference in OS was observed between HR+ and HER2+ groups. There was no significant difference in the progression interval from primary diagnosis to brain metastasis among receptor subtypes. From primary tumor to brain metastasis, receptor subtype switching occurred in 10 out of 73 patients (13.7%) for estrogen, 20 out of 70 (28.6%) for progesterone (PR), and 6 out of 72 (8.3%) for HER2. Receptor subtype switching did not significantly correlate with OS. Presence of extracranial metastases at time of BCBM diagnosis corresponded to significantly lower OS compared to no extracranial metastasis (16.5 vs 36.0 months, p = 0.01). No significant difference in OS was observed between patients with cerebral vs cerebellar brain metastases. Conclusions: These data indicate that patients with TN BCBM disease have the worst overall survival among all receptor subtypes. Metastases in extracranial sites at time of BCBM diagnosis significantly decreased survival. Location of the brain metastasis and receptor subtype switching from primary diagnosis to BCBM, which was relatively infrequent outside of the PR group, did not significantly correlate with OS in this limited data set.

Methylated p16 gene is associated with negative expression of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 in breast cancer

Objective: This study was conducted to determine the relationship between p16 gene methylation and expression of relevant receptors in breast cancer (BC) for subtyping the disease. Methods: Methylation-specific PCR (MSP) was carried out to detect the methylation status of p16 gene in 240 tissue samples and 205 serum samples from BC patients treated at our hospital. Immunohistochemistry was used to determine the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). Receiver operating characteristics (ROC) curve was analyzed for diagnostic value based on methylation status for triple-negative (TN) BC. Results: The overall methylation rates of the p16 gene were 36.7% (88/240) and 35.1% (72/205) in the tissue and serum samples, respectively. In patients with ER, PR and HER2-TNBC, the methylation rate of the p16 gene was significantly higher than that in non-triple negative patients (84.9%, 62/73) vs (25.9%, 35/135, P &lt; 0.01). The methylation of p16 gene was negatively associated with the expression of ER, PR and HER2 (r = -0.661, -0.694 and -0.765, respectively, P &lt; 0.05), but it was not correlated with the pathological characteristics of BC, such as tumor grade and lymph-node metastasis. Receiver operator characteristic (ROC) curve analysis showed that p16 gene methylation had a significant diagnostic value for TNBC with an AUC of 0.815. Therefore, p16 gene methylation is associated with the subtype of TNBC and can be used as an easy and non-invasive approach to screen patients for TNBC.

Characterization of the Relationship Between the Expression of Aspartate β-Hydroxylase and the Pathological Characteristics of Breast Cancer.

BackgroundThis study aimed to investigate the relationship between the expression of aspartate β-hydroxylase (ASPH) and the molecular mechanisms of ASPH-related genes in breast cancer (BC).Material/MethodsASPH expression was determined by immunohistochemistry and western blot analysis in samples of BC tissues and adjacent normal tissues. ASPH mRNA expression data and their clinical significance in BC were retrieved from the Oncomine and GEPIA datasets. Enrichment analysis of genes coexpressed with ASPH and annotation of potential pathways were performed with Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) analysis. Hub genes were shown in an ASPH coexpression gene-interaction network. The expression of the hub genes associated with patient survival were analyzed to determine the role of ASPH in the progression of BC.ResultsASPH levels were overexpressed in BC and correlated with cancer type, lymph node involvement, and TNM stage. Conversely, ASPH levels did not correlate with patient age, invasive carcinoma types, or molecular subtypes. Enrichment analysis showed the involvement of multiple pathways, including lipid metabolism and oxidation-reduction processes. Six hub genes, PPARG, LEP, PLIN1, AGPAT2, CAV1, and PNPLA2, were related to ASPH expression and had functional roles in the occurrence and progression of BC.ConclusionsASPH may be involved in the development of BC and may have utility as a prognostic biomarker in BC. The coexpression of ASPH-associated genes may also be beneficial in improving BC prognosis.

Germline Mutations in Latin American Women With Breast Cancer

PURPOSE Breast cancer is the most common form of cancer among women in Latin America. Limited health care access, late-stage diagnosis, and lack of knowledge on the mutation profile of cancer susceptibility genes in low- and middle-income country populations lead to higher mortality rates. To address this health disparity, this study analyzes the breast cancer mutation profile of women from Mexico and Guatemala. Results from this study can be used to improve breast cancer screenings in these countries and for Latin American women living in the United States. METHODS Genomic and clinical data of women with breast tumors were obtained at the Instituto Nacional de Salud Publica in Mexico and Instituto Nacional de Cancerologia in Guatemala. Mutations in known breast cancer susceptibility genes were identified using targeted sequencing and were validated by manual review in the Integrative Genomics Viewer and pathogenicity determined using online databases (ClinVar and Varsome). Finally, variants were compared with corresponding clinical data for population-wide trends. RESULTS The Mexico study identified 14% of cases with pathogenic mutations in a sample of 201 patients and the Guatemala study contained 11% pathogenic mutations in 673 patients. The most frequently mutated genes for both populations were BRCA1, BRCA2, PALB2, and TP53, with BRCA1/2 mutations accounting for 7% to 10% of all variants. Patients with pathogenic mutations were found to have a significantly younger age of onset than patients without mutations, and a family history of breast cancer was pronounced in patients with pathogenic mutations. CONCLUSION The results of this study increase our understanding of the molecular and pathologic characteristics of breast cancer in Latin American women. This list of pathogenic variants and their clinical characteristics should be used to inform cancer screening, diagnosis, and treatment in the United States and abroad.