Breast Cancer Survival Rates Research Articles

Transcriptional repression of p21 by EIF1AX promotes the proliferation of breast cancer cells

ObjectiveDysregulation of the cell cycle is associated with the progression of malignant cancer, but its precise functional contribution is unknown.Materials and MethodsThe expression of EIF1AX in breast cancer tissues was detected by qRT‐PCR and immunohistochemistry staining. Colony formation and tumour xenograft assays were used to examine the tumorigenesis‐associated function of EIF1AX in vitro and in vivo. RNA‐Seq analysis was used to select the downstream target genes of EIF1AX. Flow cytometry, ChIP and luciferase assays were used to investigate the molecular mechanisms by which EIF1AX regulates p21 in breast cancer cells.ResultsEIF1AX promoted breast cancer cell proliferation by promoting the G1/S cell cycle transition. A mechanistic investigation showed that EIF1AX inhibited the expression of p21, which is an essential cell cycle regulator. We identified that the transcriptional regulation of p21 by EIF1AX was p53‐independent. Clinically, EIF1AX levels were significantly elevated in breast cancer tissues, and the high level of EIF1AX was associated with lower survival rates in breast cancer patients.ConclusionsOur results imply that EIF1AX may play a key role in the incidence and promotion of breast cancer and may, thus, serve as a valuable target for breast cancer therapy.

Survival rates of advanced estrogen-receptor positive breast cancer. Analysis of 211 cases.

About 80% of breast cancer (BC) cases express estrogen receptor (ER), which has been correlated with good prognosis and response to estrogen deprivation Aim: To characterize ER positive advanced BC (ABC) patients treated at our institution assessing the impact of clinical pre-sentation (stage IV, de novo disease at diagnosis versus systemic recurrence) and BC subtype on survival rates. We evaluated 211 ER+ advanced BC (ABC) patients, treated between 1997 and 2017. The median overall survival (OS) was 37 months. Median OS for the period 1997/2006 and 2007/2017 were 33 and 42 months, respectively (p = 0.47). Luminal A, ABC stage IV disease at diagnosis displayed better OS rates than Luminal B stage IV tumors (100 and 32 months respectively, p < 0.01). Clinical presentation (stage IV vs. systemic recurrence) and tumor subtype are key determinants of OS in ABC.

Molecular and Cellular Factors Associated with Racial Disparity in Breast Cancer.

Recent studies have demonstrated that racial differences can influence breast cancer incidence and survival rate. African American (AA) women are at two to three fold higher risk for breast cancer than other ethnic groups. AA women with aggressive breast cancers show worse prognoses and higher mortality rates relative to Caucasian (CA) women. Over the last few years, effective treatment strategies have reduced mortality from breast cancer. Unfortunately, the breast cancer mortality rate among AA women remains higher compared to their CA counterparts. The focus of this review is to underscore the racial differences and differential regulation/expression of genetic signatures in CA and AA women with breast cancer. Moreover, immune cell infiltration significantly affects the clinical outcome of breast cancer. Here, we have reviewed recent findings on immune cell recruitment in the tumor microenvironment (TME) and documented its association with breast cancer racial disparity. In addition, we have extensively discussed the role of cytokines, chemokines, and other cell signaling molecules among AA and CA breast cancer patients. Furthermore, we have also reviewed the distinct genetic and epigenetic changes in AA and CA patients. Overall, this review article encompasses various molecular and cellular factors associated with breast cancer disparity that affects mortality and clinical outcome.

Decreased expression of the thyroid hormone-inactivating enzyme type 3 deiodinase is associated with lower survival rates in breast cancer

Thyroid hormones (THs) are critical regulators of cellular processes, while changes in their levels impact all the hallmarks of cancer. Disturbed expression of type 3 deiodinase (DIO3), the main TH-inactivating enzyme, occurs in several human neoplasms and has been associated with adverse outcomes. Here, we investigated the patterns of DIO3 expression and its prognostic significance in breast cancer. DIO3 expression was evaluated by immunohistochemistry in a primary cohort of patients with breast cancer and validated in a second cohort using RNA sequencing data from the TCGA database. DNA methylation data were obtained from the same database. DIO3 expression was present in normal and tumoral breast tissue. Low levels of DIO3 expression were associated with increased mortality in the primary cohort. Accordingly, low DIO3 mRNA levels were associated with an increased risk of death in a multivariate model in the validation cohort. DNA methylation analysis revealed that the DIO3 gene promoter is hypermethylated in tumors when compared to normal tissue. In conclusion, DIO3 is expressed in normal and tumoral breast tissue, while decreased expression relates to poor overall survival in breast cancer patients. Finally, loss of DIO3 expression is associated with hypermethylation of the gene promoter and might have therapeutic implications.

Abstract 2844: New breast cancer protein as a potential biomarker in liquid biopsies

Abstract The decline in breast cancer mortality over the past 2 decades is primarily the result of advances in early detection and treatment. However, the five year relative survival rate of metastatic breast cancer (MBC) patients is only 27%. This requires the need of new biomarkers for early detection of MBC. Tumors secrete microvesicles (MV) in large quantities to blood circulation in order to communicate with distant cells such as immune cells and prepare the metastatic niche. Our recent studies showed that MV from metastatic breast cancer cells contain a specific peptide from the a2 isoform vacuolar ATPase (a2NTD). This a2NTD is undetectable in mammary epithelial cells MV but expressed abundantly by MV produced by breast tumor cells. We have previously shown that the MV containing a2NTD modulate immune cells, promotes tumor growth, metastasis and positively correlates with the invasiveness of breast cancer cells. Identifying the role of a2NTD in regulating immune cells in liquid biopsy will provide a new biomarker for breast cancer. Treatment of whole blood from healthy volunteers with MDA MB-231 MV or recombinant a2NTD drives the neutrophil transition from High density neutrophils (HDN) to Low density neutrophils (LDN). Flow cytometrical analysis showed that LDN possess the PMN-MDSCs markers CD11b+ CD15+ CD14- CD33- HLA-DR-. In addition a2NTD treatment was associated with decreased internal staining of Arg-1 in neutrophils that suggests the release of Arg-1. This data suggest that a2NTD can reprogram neutrophils to exert immunosuppressive phenotype. Further characterization of surface markers as well as functional assays demonstrate the exact phenotype of neutrophils. Together studying the impact of a2NTD present in MV on immune alteration during metastasis can be potential predictors of the growth and metastasis of breast cancer. Citation Format: Safaa A. Ibrahim, Valerie riehl, Kenneth D. Beaman. New breast cancer protein as a potential biomarker in liquid biopsies [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2844.

The five-year survival rate of breast cancer at Radiation and Isotopes Centre Khartoum, Sudan

BackgroundThe Radiation and Isotopes Centre Khartoum (RICK) is the largest public cancer centre in Sudan. The most common cancer in Sudan (and RICK) is breast cancer. The study aims to determine the five year survival of breast cancer as well as factors influencing this survivorship. MethodsThis retrospective facility-based study was conducted on patients diagnosed as having breast cancer at RICK during the year 2013. At 305 patients, the population under study was totally covered. Data analysis was conducted using SPSS version 23. Kaplan-Meier method was used to estimate survival, and to further plot it against specific variables. ResultsThe five-year survival was found to be 79%. Lymph nodes were involved in 70.5% of the cases. The mean time between patients’ first discovery of symptoms and diagnosis at RICK was 13.03 months. Presence of comorbid diabetes and hypertension significantly increased breast cancer mortality. ConclusionsBreast cancer in Sudan is characterized by younger age, delayed diagnosis and advanced staging at presentation, as well as lower five-year breast cancer survival in comparison to developed countries.

PET-CT upstaging of unilateral operable breast cancer and its correlation with molecular subtypes.

Context:Prognosis and survival rates for breast cancer vary greatly depending on the cancer stage of the patient. Instead of a step-by-step approach using multiple investigations, we can get all the information about the metastatic load of the disease in PET-CT imaging by one single investigation. There is also a correlation between prognosis, FDG uptake, and molecular subtype of breast cancer (Luminal A, Luminal B, Human epidermal growth factor receptor 2 (HER2) positive and Triple-negative). Pre-treatment baseline PET-CT scan was done in 156 unilateral early and operable breast cancer patients from November 2017 to April 2019 in our prospective observational study.Aims: To evaluate the utility of PET-CT in staging and upstaging of early and operable breast cancer by detection of unsuspected lymph nodes and distant organ metastases.To determine the prognostic association between SUVmax of the primary breast lesion in the upstaged cases and the molecular subtypes. Results: Thus, PET-CT can serve as one-stop imaging in unilateral operable early breast cancer patients for upstaging and prognostication based on the correlation of SUVmax with molecular subtypes of breast lesions in patients who will surely benefit from whole-body imaging.Out of 156 patients, approximately 27 patients were upstaged after pre-treatment PET CT.Six patients were upstaged to stage IIIC and 21 patients were upstaged to IV.Regional nodes like internal mammary and supraclavicular nodes were detected in 7 patients and 5 patients, respectively, out of 156 patients.Non-regional distant nodes and organ metastases were detected in 11 and 18 patients out of 156 patients.Most common molecular subtype detected in the upstaged cases in our study was Luminal A (13 patients) followed by Triple negative (6), Luminal B (3) and HER2-neu-positive subtypes (1). Conclusions: FDG PET-CT is a substantial modality to provide information on regional, non regional lymph nodes and distant metastases in early operable breast cancer.It helps in evaluating the whole body metastatic burden in a single sitting, therefore, reducing the need for multiple investigations.SUVmax association of the index lesion with molecular subtype in the FDG PET scanning can serve as a prognostication factor in operable early breast cancer patients.

Determination of Relative Frequency of Calretinin Expression in Patients with Breast Cancer in Yazd, Iran

Introduction: Breast cancer is known as the most common type of cancer among women in the world. Several methods have been proposed to predict the behavior of breast carcinoma. Recently calretinin has been found to be a reliable factor in predicting tumor survival rate in breast cancer. The aim of this study was to evaluate the relative frequency of calretinin expression in patients with breast cancer in Yazd,Iran. Material and methods: In this cross-sectional retrospective study, the clinicopathologic features and the outcome of patients with breast cancer from 2017 to 2018 were reviewed at Shahid Sadoughi Hospital, Yazd, Iran. The influence of potential prognostic parameters in the overall survival was investigated by log-rank test and Cox regression analysis. Results: Among 100 cases with breast carcinoma, 14.5% were positive for calretinin. The distribution of the rate of positivity of IHC markers including ER, PR, P53, Ki67 and Her2 was 62.9%, 57.1%, 46.2%, 80.5% and 22.1%, respectively. The most common grade and stage were grade2 and stage3 respectively. There was no significant difference in the status of IHC markers (including ER, PR, Her2 and Ki67) in terms of calretinin. 66.7% of the patients with calretinin positive results were P53 positive. The results of the mean tumor size distribution in the two groups of positive and negative calretinin showed a significant difference (P-value = 0.05). A lower age at the time of diagnosis was found in patients with calretinin positive results (P-value = 0.119). The mean survival rate in calretinin positive group was 6.71 years and 6.62 years in calretinin negative patients which was not statistically significant. Conclusion: The results of this study indicated an association between calretinin expression and other IHC markers (although not statistically significant) in predicting poor prognosis in breast cancer patients. In addition, we found a statistically significant association among calretinin with smaller tumor size and lower age at the time of diagnosis in patients with breast cancer.

A novel approach to identify subtype-specific network biomarkers of breast cancer survivability

Increasing the survival rates for breast cancer has gained significant researcher interest. However, current studies reveal that a small subset of gene makers can predict survivability for people with different breast cancer subtypes. In these studies, the selected genes are not necessarily functionally related, and hence, they may not correctly indicate the molecular mechanism behind breast cancer survivability. Also, several studies have shown there is a very low overlap between the biomarkers subsets for the same cancer disease. To improve the robustness of the classification performance and stability of detected biomarkers, recent methods involve taking existing knowledge on relations between genes into account in the classifier by aggregating functionality-related genes to produce discriminative gene subnetworks called network biomarkers. In this paper, using a dataset of patients with different subtypes of breast cancer, we devised a novel network-based approach by integrating a protein–protein interaction (PPI) network with gene expression data to (1) identify the network biomarkers (metagene) of breast cancer survivability and (2) predict the survivability of breast cancer patients based on their subtypes of breast cancer. Our method involves using the concept of seed genes for the identification of network biomarkers, ADASYN to solve class-imbalance, and random forest to predict the survivability of patients. We obtained the best classification performance with distance three from seed gene protein where the Gmean, F1-measure, and accuracy were respectively 0.900, 0.800, and 90.34%. The maximum size of a network biomarker with distance 3 is 9. A maximum of 34 genes is needed to accurately predict the survivability of breast cancer patients. This method can be used to identify the survivability of breast cancer patients using gene relationship networks. It has high prediction performance, including specificity and sensitivity for both cohorts of survivals and deceased.

Survival Rate and Prognostic Factors among Iranian Breast Cancer Patients

Survival time is one of the indicators used for evaluation of the quality of care in different types of malignancies, including breast cancer. The present study aimed to estimate the survival rate of breast cancer and its related factors among Iranian patients. Overall, 3148 cases of breast cancer who referred to the Cancer Research Center in Shahid Beheshti University of Medical Sciences, Tehran, Iran during 1994-2017 participated in this longitudinal study. Survival estimates were calculated using the Kaplan-Meier method and the Bayesian generalized Birnbaum-Saunders model with cure rate from geometric distribution. Clinical, pathological, and biological variables as potential prognostic factors were entered in univariate and multivariate analyses.In order to identify the significant prognostic factors, 95% highest posterior density (HPD) intervals were used. The overall 1, 5, 10, 15, 20 and 25-year survival rate were 95%, 75%, 60%, 47%, 46% and 46%, respectively. A significant relation was observed between survival time and the variables such as age, size of tumor, number of lymph nodes, stage, histological grade, estrogen receptor, progesterone receptor, and lymphovascular invasion. The findings of this study might help the health managers to plan long-term programs considering regional determinants, public education, and screening for early detection of breast cancer cases which can eventually influence the overall survival rate of these patients.

Relationship of Socio Economic Status, Income, and Education with the Survival Rate of Breast Cancer: A Meta-Analysis

Despite our awareness of the significant effect of Social Determinant of Health (SDoH) such as Socio Economic Status (SES), income and education on breast cancer survival, there was a serious lack of information about the effect of different level of these factors on breast cancer survival. So far, no meta-analysis has been conducted with this aim, but this gap was addressed by this meta-analysis. Main electronic databases such as PubMed, Web of Science, and Scopus were investigated up to January 2019. Epidemiological studies focusing on the association between SDoH and breast cancer were singled out. Q-test and I2 statistic were used to study the heterogeneity across studies. Begg's and Egger's tests were applied to explore the likelihood of the publication bias. The results were reported as hazard ratio (HR) with 95% confidence intervals (CI) through a random-effects model. We identified 7,653 references and included 25 studies involving 1,497,881 participants. The HR estimate of breast cancer survival was 0.82 (0.67, 0.98) among high level of SES, 0.82 (0.70, 0.94) among high level of income and 0.72 (0.66, 0.78) among academic level of education. The SES, income, and education were associated with breast cancer survival, although the association was not very strong. However, there was a significant association between the levels of these factors and breast cancer survival.

Golgi-Localized PAQR4 Mediates Antiapoptotic Ceramidase Activity in Breast Cancer.

The metabolic network of sphingolipids plays important roles in cancer biology. Prominent sphingolipids include ceramides and sphingosine-1-phosphate that regulate multiple aspects of growth, apoptosis, and cellular signaling. Although a significant number of enzymatic regulators of the sphingolipid pathway have been described in detail, many remained poorly characterized. Here we applied a patient-derived systemic approach to identify and molecularly define progestin and adipoQ receptor family member IV (PAQR4) as a Golgi-localized ceramidase. PAQR4 was approximately 5-fold upregulated in breast cancer compared with matched control tissue and its overexpression correlated with disease-specific survival rates in breast cancer. Induction of PAQR4 in breast tumors was found to be subtype-independent and correlated with increased ceramidase activity. These findings establish PAQR4 as Golgi-localized ceramidase required for cellular growth in breast cancer. SIGNIFICANCE: Induction of and cellular dependency on de novo sphingolipid synthesis via PAQR4 highlights a central vulnerability in breast cancer that may serve as a viable therapeutic target.

Abstract C020: Regularized multiple mediation analysis for big data set—With an application to explore racial disparity in breast cancer survival

Abstract Mediation effect refers to the effect conveyed by a third variable, the mediator, to an observed relationship between an exposure and a response variable of interest. Mediation analysis is used widely in fields such as social science, prevention study, behavior research, and epidemiology. For example, it has been well established that low socioeconomic status is associated with poor health status. To reduce this health disparity, investigators would need to quantify the effects, called mediation effects, from different risk factors that intervene in the relationship between the socioeconomic status and health outcomes, so that efficient interventions can be carried out. The general multiple mediation analysis method, proposed by Yu et al., improved traditional methods (e.g., estimation of natural and controlled direct effects) to enable consideration of multiple mediators simultaneously and the use of linear and nonlinear predictive models for estimating mediation effects. A big data set includes a large number of variables. Within big data mediation analysis, the number of potential mediators is big. For example, in explaining the racial disparity in breast cancer survival, there are a lot of risk factors that need to be considered such as individual behaviors, environmental factors, social-economic status, treatment effects, diagnosis characters, and even gene expression variables. In this study, we propose to use a regularized mediation analysis method that identifies significant mediators and estimates their indirect effects simultaneously. Breast cancer is the most common cancer and the second leading cause of cancer death among women of all races. Despite the improvement of survival rates of breast cancer in the U.S., a significant difference between white and black women remains. Due to limitations of current analytic methods and the lack of comprehensive data sets, researchers have not been able to differentiate the relative effect that each factor contributes to the overall racial disparity. We use the CDC-funded Patterns of Care study and Enhancing Cancer Registry Data for Comparative Effectiveness Research study to examine the determinants of racial disparities in breast cancer survival using the propose regularized multiple mediation analysis. Using the proposed method, we identified important factors that explain the racial disparity in breast cancer survival, which includes the cancer stage-related variables (stage, tumor size, lymph nodes involvement, extension, and tumor size), molecular subtype, treatment methods such as surgery and hormonal therapy, and tumor grade. Age also contributed to the racial differences, but in an opposite direction. Black patients are more likely to be diagnosed at a younger age, which is related with better survival outcomes. Overall, we found that all racial disparity in survival among Louisiana breast cancer patients was explained by factors included in the study. Citation Format: Qingzhao Yu, Lu Zhang, Meichin Hsieh, Xiaocheng Wu, Richard A Scribner, Bin Li. Regularized multiple mediation analysis for big data set—With an application to explore racial disparity in breast cancer survival [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C020.

Abstract D008: Resolving disparities in cancer patient outcomes in Trinidad and Tobago

Abstract The Caribbean Cancer Research Initiative (CCRI) began as a result of the alarming rates of various cancer types in the Caribbean and the lack of data and credible sources of information on the prevalence of cancer in the region. What we do know is that Trinidad and Tobago has one of the highest cancer mortality rates in the Caribbean. Some explanations for this disparity can be lack of treatment innovation, educational gaps regarding screening, shortcomings in health care administration and cultural biases. Preliminary data indicates that Trinidad has one of the highest breast cancer mortality rates in the Americas. The five year breast cancer survival rate is at approximately 30% compared to over 90% in the US. The median time to diagnostic resolution based on preliminary research is 65 days, approximately 3 times what is it in US and Canada. CCRI’s mission is to build the cancer research capacity in the Caribbean starting in Trinidad which will aid in preventing more cancers and improving patient outcomes in the Caribbean. One of the main programs of the organization is the patient navigation service which is designed to meet the needs of persons diagnosed with cancer and their family members. This service has highlighted some of the contributing factors to cancer disparities in Trinidad. Examples of these that will be featured on this poster are socioeconomic factors, cultural phenomenon, geographical factors and poor access to proper care. The Caribbean Cancer Research Initiative is committed to assist patients to overcome their barriers to gain better outcomes, which will aid in resolving disparities in cancer health in Trinidad. Citation Format: Nalisha Monroe. Resolving disparities in cancer patient outcomes in Trinidad and Tobago [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr D008.

Exploring Strategies for Using Social Media to Self-Manage Health Care When Living With and Beyond Breast Cancer: In-Depth Qualitative Study.

BackgroundAs breast cancer survival rates improve and structural health resources are increasingly being stretched, health providers require people living with and beyond breast cancer (LwBBC) to self-manage aspects of their care.ObjectiveThis study aimed to explore how women use and experience social media to self-manage their psychosocial needs and support self-management across the breast cancer continuum.MethodsThe experiences of 21 women (age range 27-64 years) were explored using an in-depth qualitative approach. The women varied in the duration of their experiences of LwBBC, which facilitated insights into how they evolve and change their self-management strategies over time. Semistructured interviews were analyzed inductively using a thematic analysis, a polytextual analysis, and voice-centered relational methods.ResultsThe use of multiple social media platforms, such as YouTube, Facebook, WhatsApp, and Twitter, enabled women to self-manage aspects of their care by satisfying needs for timely, relevant, and appropriate support, by navigating identities disrupted by diagnosis and treatment and by allowing them to (re)gain a sense of control. Women described extending their everyday use of multiple platforms to self-manage their care. However, women experienced social media as both empowering and dislocating, as their engagement was impacted by their everyday experiences of LwBBC.ConclusionsHealth care professionals (HCPs) need to be more aware, and open to the possibilities, of women using multiple social media resources as self-management tools. It is important for HCPs to initiate value-free discussions and create the space necessary for women to share how social media resources support a tailored and timely self-managed approach to their unique psychosocial needs.

The pink vans: Bringing cancer screening closer to home.

e14021 Background: A global survey reported that among 15 Asian countries, the Philippines has the highest breast cancer mortality rate and the lowest mortality-to-incidence ratio. This may be due to the fact that majority of breast cancers are diagnosed in locally advanced or metastatic stages among low- and middle-income countries. Studies show that in the Philippines more than half (53%) of patients with breast cancer were diagnosed at stages III and IV, while only 2-3% of cases were treated at Stage I. This translates to a dismal 58.6 % 5-year survival rate. Furthermore, socioeconomic factors were identified as one of the major causes for the lack of access to early detection and treatment. These include lower educational level, higher poverty rates, inadequate or no health insurance, lack of transportation, and/or the unavailability of health services in far-flung areas. These findings are currently of urgent national concern since the improvements in breast cancer survival rates brought by advances in treatments are mainly dependent on early detection, screening and timely treatment. Methods: In response to this gap in the delivery of services to promote early cancer detection, the University of the Philippines – Philippine General Hospital (UP-PGH) Cancer Institute established the Mobile Breast Cancer Diagnostic Clinic Program, a first in the country where two fully equipped “pink” vans are sent out to far flung areas and provide breast cancer screening and diagnostic services (eg. Mammogram, breast ultrasound, biopsies of suspicious masses, etc). These vans are manned by medical and surgical oncologists, and various paramedical professionals. Results: In the first 6 months of the program, the “pink” vans were able to visit 3 strategically identified areas in the country. These three tours have served a total of 189 women who all underwent screening mammography. 18 had their suspicious lesions biopsied, and two-thirds of which were found to be malignant. These patients were then referred to our institution for further work-up and management. Conclusions: As the Philippine health department continues to emphasize clinical and self-breast exam as part of its breast cancer control program, efforts like the UP-PGH “Pink Vans” may eventually help supplement the gap in the country’s breast cancer screening endeavors with the goal of improving survival by identifying the disease at its earliest stage.

Disparities in Genetic Testing and Care among Black women with Hereditary Breast Cancer.

Despite a steady improvement in breast cancer survival rates over the past several decades, mortality disparities remain among Black women, who have a 42% higher death rate compared to non-Hispanic white (NHW) women. Hereditary breast cancer (HBC) accounts for 5-10% of all breast cancer cases, the majority of which are due to the BRCA1 and BRCA2 (BRCA) genes. Despite the availability of BRCA testing for over 25 years, there remain disproportionately lower rates of genetic testing among Blacks compared to NHW due to a multitude of factors. The intent of this review is to discuss racial disparities focused on HBC across diverse populations and review the existing gaps to be addressed when delivering gene-based care. The factors contributing to the racial survival disparity are undoubtedly complex and likely an interplay between tumor biology, genomics, patterns of care and socioeconomic factors. Advances in genomic technologies that now allow for full characterization of germline DNA sequencing are integral in defining the complex and multifactorial cause of breast cancer and may help to explain the existing racial survival disparities. Identification of inherited cancer risk may lead to cancer prevention, early cancer detection, treatment guidance, and ultimately has great potential to improve outcomes. Consequently, advances in HBC diagnosis and treatment without widespread implementation have the potential to further widen the existing breast cancer mortality gap between Black and NHW women.

Identification of ALDH1A3 as a Viable Therapeutic Target in Breast Cancer Metastasis-Initiating Cells.

The development of efficacious therapies targeting metastatic spread of breast cancer to the brain represents an unmet clinical need. Accordingly, an improved understanding of the molecular underpinnings of central nervous system spread and progression of breast cancer brain metastases (BCBM) is required. In this study, the clinical burden of disease in BCBM was investigated, as well as the role of aldehyde dehydrogenase 1A3 (ALDH1A3) in the metastatic cascade leading to BCBM development. Initial analysis of clinical survival trends for breast cancer and BCBM determined improvement of breast cancer survival rates; however, this has failed to positively affect the prognostic milestones of triple-negative breast cancer (TNBC) brain metastases (BM). ALDH1A3 and a representative epithelial-mesenchymal transition (EMT) gene signature (mesenchymal markers, CD44 or Vimentin) were compared in tumors derived from BM, lung metastases (LM), or bone metastases (BoM) of patients as well as mice after injection of TNBC cells. Selective elevation of the EMT signature and ALDH1A3 were observed in BM, unlike LM and BoM, especially in the tumor edge. Furthermore, ALDH1A3 was determined to play a role in BCBM establishment via regulation of circulating tumor cell adhesion and migration phases in the BCBM cascade. Validation through genetic and pharmacologic inhibition of ALDH1A3 via lentiviral shRNA knockdown and a novel small-molecule inhibitor demonstrated selective inhibition of BCBM formation with prolonged survival of tumor-bearing mice. Given the survival benefits via targeting ALDH1A3, it may prove an effective therapeutic strategy for BCBM prevention and/or treatment.

A Model Selection Approach for Variable Selection with Censored Data

We consider the variable selection problem when the response is subject to censoring. A main particularity of this context is that information content of sampled units varies depending on the censoring times. Our approach is based on model selection where all 2k possible models are entertained and we adopt an objective Bayesian perspective where the choice of prior distributions is a delicate issue given the well-known sensitivity of Bayes factors to these prior inputs. We show that borrowing priors from the ‘uncensored’ literature may lead to unsatisfactory results as this default procedure implicitly assumes a uniform contribution of all units independently on their censoring times. In this paper, we develop specific methodology based on a generalization of the g-priors, explicitly addressing the particularities of survival problems arguing that it behaves comparatively better than standard approaches on the basis of arguments specific to variable selection problems (like e.g. predictive matching) in the particular case of the accelerated failure time model with lognormal errors. We apply the methodology to a recent large epidemiological study about breast cancer survival rates in Castellón, a province of Spain.

Estrogen-regulated PTTG1 promotes breast cancer progression by regulating cyclin kinase expression

BackgroundThe present study aims to investigate the effects of pituitary tumor transforming gene (PTTG) 1 on breast cancer and its underlying mechanism.MethodsGEO data set was applied to analyze the relationship between PTTG1 and survival status and the TCGA breast cancer dataset was used to explore its possible targets. The stable cell lines including PTTG1 knockdown cells, estrogen receptor (ESR) 1 knockdown cells, and PTTG1 overexpression cells were constructed. MTT was used to determine cell viabilities. Propidium iodide (PI) staining and flow cytometry were used to analyze the cell cycle. Quantitative polymerase chain reaction (qPCR) was employed to determine the mRNA expressions. Points mutations and luciferase reporter assays were used to determine the binding sites of estrogen.ResultsPTTG1 was associated with poor survival rates in breast cancer. In vitro study demonstrated that PTTG1 affected cell viabilities of MCF7 and T47D cells. Besides, PTTG1 affected cell cycle arrest of breast cancer cells. Overexpression of PTTG1 led to more breast cancer cells distributed in S phase. The levels of PTTG1 were associated with estrogen and further results showed that the levels of PTTG1 were positively correlated to tamoxifen resistance. Two genes including CCNA2 and CCNB2 were identified to be possible targets of PTTG1.ConclusionEstrogen-regulated PTTG1 promotes the development of breast cancer cells by the regulation of the cell cycle.