Benign Thyroid Diseases and the Risk of Death from Breast Cancer

Abstract Biopterin as a stable metabolite is produced by oxidation of 5,6,7,8-tetrahydrobiopterin (BH4). It is known that many diseases may cause changes in BH4 concentration and/or dihydropteridine reductase (DHPR) enzyme activity. There is only a limited number of studies correlating DHPR activity in malignancies. The main goal of the present study was to evaluate alterations in the DHPR activity and biopterin levels in patients with breast and thyroid cancers. The breast cancer patients (n=24) were compared to patients with benign breast diseases (n=19) and controls (n=30). In addition; the patients with thyroid cancer (n=17) were compared to patients with benign thyroid diseases (n=42) and the control group. We did not observe any significant difference between the benign disorders and the malignancies. Biopterin concentrations in patients with benign and malign thyroid and breast diseases were lower than the controls (all p <0.05). DHPR activities in thyroid diseases were significantly higher than the controls while insignificant decreases in DHPR activities in breast patients were detected. Our results suggested significant alterations in unconjugated pteridine pathway in thyroid and breast disorders.

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Guideline for radioiodine therapy for benign thyroid diseases (version 3)

Nuklearmedizin ◽

10.1055/s-0038-1623919 ◽

2004 ◽

Vol 43 (06) ◽

pp. 217-220 ◽

Cited By ~ 8

Author(s):

J. Dressler ◽

F. Grünwald ◽

B. Leisner ◽

E. Moser ◽

Chr. Reiners ◽

...

Keyword(s):

Radioiodine Therapy ◽

Thyroid Volume ◽

Thyroid Diseases ◽

Antithyroid Drugs ◽

Graves Disease ◽

Co Morbidity ◽

History Of ◽

Individual Decisions ◽

Prophylactic Use ◽

Benign Thyroid

SummaryThe version 3 of the guideline for radioiodine therapy for benign thyroid diseases presents first of all a revision of the version 2. The chapter indication for radioiodine therapy, surgical treatment or antithyroid drugs bases on an interdisciplinary consensus. The manifold criteria for decision making consider the entity of thyroid disease (autonomy, Graves’ disease, goitre, goitre recurrence), the thyroid volume, suspicion of malignancy, cystic nodules, risk of surgery and co-morbidity, history of subtotal thyroidectomy, persistent or recurrent thyrotoxicosis caused by Graves’ disease including known risk factors for relapse, compression of the trachea caused by goitre, requirement of direct therapeutic effect as well as the patient’s preference. Because often some of these criteria are relevant, the guideline offers the necessary flexibility for individual decisions. Further topics are patients’ preparation, counseling, dosage concepts, procedural details, results, side effects and follow-up care. The prophylactic use of glucocorticoids during radioiodine therapy in patients without preexisting ophthalmopathy as well as dosage and duration of glucocorticoid medication in patients with preexisting ophthalmopathy need to be clarified in further studies. The pragmatic recommendations for the combined use of radioiodine and glucocorticoids remained unchanged in the 3rd version.

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De-escalation of radiation therapy in patients with stage I, node-negative, HER2-positive breast cancer

npj Breast Cancer ◽

10.1038/s41523-021-00242-8 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Jose G. Bazan ◽

Sachin R. Jhawar ◽

Daniel Stover ◽

Ko Un Park ◽

Sasha Beyer ◽

...

Keyword(s):

Breast Cancer ◽

Early Stage ◽

Local Therapy ◽

Adjuvant Radiation ◽

Her2 Positive ◽

Node Negative ◽

Risk Of Death ◽

Her2 Breast Cancer ◽

Neoadjuvant Systemic Therapy ◽

Increased Risk

AbstractIn the modern era, highly effective anti-HER2 therapy is associated with low local-regional recurrence (LRR) rates for early-stage HER2+ breast cancer raising the question of whether local therapy de-escalation by radiation omission is possible in patients with small-node negative tumors treated with lumpectomy. To evaluate existing data on radiation omission, we used the National Cancer Database (NCDB) to test the hypothesis that RT omission results in equivalent overall survival (OS) in stage 1 (T1N0) HER2+ breast cancer. We excluded patients that received neoadjuvant systemic therapy. We stratified the cohort by receipt of adjuvant radiation. We identified 6897 patients (6388 RT; 509 no RT). Patients that did not receive radiation tended to be ≥70 years-old (odds ratio [OR] = 3.69, 95% CI: 3.02–4.51, p < 0.0001), to have ≥1 comorbidity (OR = 1.33, 95% CI: 1.06–1.68, p = 0.0154), to be Hispanic (OR = 1.49, 95% CI: 1.00–2.22, p = 0.049), and to live in lower income areas (OR = 1.32, 95% CI: 1.07–1.64, p = 0.0266). Radiation omission was associated with a 3.67-fold (95% CI: 2.23–6.02, p < 0.0001) increased risk of death. While other selection biases that influence radiation omission likely persist, these data should give caution to radiation omission in T1N0 HER2+ breast cancer.

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Surgery for primary tumor benefits survival for breast cancer patients with bone metastases: a large cohort retrospective study

BMC Cancer ◽

10.1186/s12885-021-07964-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Zhangheng Huang ◽

Xin Zhou ◽

Yuexin Tong ◽

Lujian Zhu ◽

Ruhan Zhao ◽

...

Keyword(s):

Breast Cancer ◽

Prognostic Factors ◽

Bone Metastases ◽

Cancer Patients ◽

Primary Tumor ◽

Predictive Accuracy ◽

Rank Test ◽

Breast Cancer Patients ◽

Risk Of Death ◽

The Impact

Abstract Background The role of surgery for the primary tumor in breast cancer patients with bone metastases (BM) remains unclear. The purpose of this study was to determine the impact of surgery for the primary tumor in breast cancer patients with BM and to develop prognostic nomograms to predict the overall survival (OS) of breast cancer patients with BM. Methods A total of 3956 breast cancer patients with BM from the Surveillance, Epidemiology, and End Results database between 2010 and 2016 were included. Propensity score matching (PSM) was used to eliminate the bias between the surgery and non-surgery groups. The Kaplan-Meier analysis and the log-rank test were performed to compare the OS between two groups. Cox proportional risk regression models were used to identify independent prognostic factors. Two nomograms were constructed for predicting the OS of patients in the surgery and non-surgery groups, respectively. In addition, calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) were used to evaluate the performance of nomograms. Result The survival analysis showed that the surgery of the primary tumor significantly improved the OS for breast cancer patients with BM. Based on independent prognostic factors, separate nomograms were constructed for the surgery and non-surgery groups. The calibration and ROC curves of these nomograms indicated that both two models have high predictive accuracy, with the area under the curve values ≥0.700 on both the training and validation cohorts. Moreover, DCA showed that nomograms have strong clinical utility. Based on the results of the X-tile analysis, all patients were classified in the low-risk-of-death subgroup had a better prognosis. Conclusion The surgery of the primary tumor may provide survival benefits for breast cancer patients with BM. Furthermore, these prognostic nomograms we constructed may be used as a tool to accurately assess the long-term prognosis of patients and help clinicians to develop individualized treatment strategies.

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Key Genes and Prognostic Analysis in HER2+ Breast Cancer

Technology in Cancer Research & Treatment ◽

10.1177/1533033820983298 ◽

2021 ◽

Vol 20 ◽

pp. 153303382098329

Author(s):

Yujie Weng ◽

Wei Liang ◽

Yucheng Ji ◽

Zhongxian Li ◽

Rong Jia ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Differentially Expressed Genes ◽

Protein Interaction ◽

Differentially Expressed ◽

Protein Kinase Activity ◽

Protein Protein Interaction ◽

Risk Of Death ◽

Her2 Breast Cancer ◽

Key Genes

Human epidermal growth factor 2 (HER2)+ breast cancer is considered the most dangerous type of breast cancers. Herein, we used bioinformatics methods to identify potential key genes in HER2+ breast cancer to enable its diagnosis, treatment, and prognosis prediction. Datasets of HER2+ breast cancer and normal tissue samples retrieved from Gene Expression Omnibus and The Cancer Genome Atlas databases were subjected to analysis for differentially expressed genes using R software. The identified differentially expressed genes were subjected to gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses followed by construction of protein-protein interaction networks using the STRING database to identify key genes. The genes were further validated via survival and differential gene expression analyses. We identified 97 upregulated and 106 downregulated genes that were primarily associated with processes such as mitosis, protein kinase activity, cell cycle, and the p53 signaling pathway. Visualization of the protein-protein interaction network identified 10 key genes ( CCNA2, CDK1, CDC20, CCNB1, DLGAP5, AURKA, BUB1B, RRM2, TPX2, and MAD2L1), all of which were upregulated. Survival analysis using PROGgeneV2 showed that CDC20, CCNA2, DLGAP5, RRM2, and TPX2 are prognosis-related key genes in HER2+ breast cancer. A nomogram showed that high expression of RRM2, DLGAP5, and TPX2 was positively associated with the risk of death. TPX2, which has not previously been reported in HER2+ breast cancer, was associated with breast cancer development, progression, and prognosis and is therefore a potential key gene. It is hoped that this study can provide a new method for the diagnosis and treatment of HER2 + breast cancer.

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Phenotypic discordance between primary and metastatic breast cancer in the large-scale real-life multicenter French ESME cohort

npj Breast Cancer ◽

10.1038/s41523-021-00252-6 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Thomas Grinda ◽

Natacha Joyon ◽

Amélie Lusque ◽

Sarah Lefèvre ◽

Laurent Arnould ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Large Scale ◽

Tumour Progression ◽

Primary Tumour ◽

Multivariable Analysis ◽

Real Life ◽

Metastatic Breast ◽

Her2 Status ◽

Risk Of Death

AbstractExpression of hormone receptor (HR) for estrogens (ER) and progesterone (PR) and HER2 remains the cornerstone to define the therapeutic strategy for breast cancer patients. We aimed to compare phenotypic profiles between matched primary and metastatic breast cancer (MBC) in the ESME database, a National real-life multicenter cohort of MBC patients. Patients with results available on both primary tumour and metastatic disease within 6 months of MBC diagnosis and before any tumour progression were eligible for the main analysis. Among the 16,703 patients included in the database, 1677 (10.0%) had available biopsy results at MBC diagnosis and on matched primary tumour. The change rate of either HR or HER2 was 27.0%. Global HR status changed (from positive = either ER or PR positive, to negative = both negative; and reverse) in 14.2% of the cases (expression loss in 72.5% and gain in 27.5%). HER2 status changed in 7.8% (amplification loss in 45.2%). The discordance rate appeared similar across different biopsy sites. Metastasis to bone, HER2+ and RH+/HER2- subtypes and previous adjuvant endocrine therapy, but not relapse interval were associated with an HR discordance in multivariable analysis. Loss of HR status was significantly associated with a risk of death (HR adjusted = 1.51, p = 0.002) while gain of HR and HER2 discordance was not. In conclusion, discordance of HR and HER2 expression between primary and metastatic breast cancer cannot be neglected. In addition, HR loss is associated with worse survival. Sampling metastatic sites is essential for treatment adjustment.

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Impact of Medicaid expansion on two-year mortality among stage IV breast cancer (BC) patients according to race.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.6525 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 6525-6525

Author(s):

Catalina Malinowski ◽

Xiudong Lei ◽

Hui Zhao ◽

Sharon H. Giordano ◽

Mariana Chavez Mac Gregor

Keyword(s):

Breast Cancer ◽

Low Income ◽

Stage Iv ◽

Medicaid Expansion ◽

Risk Of Death ◽

Stage Iv Breast Cancer ◽

Increased Risk ◽

The Impact ◽

Expansion Period ◽

White Patients

6525 Background: Inadequate access to healthcare services is associated with worse outcomes. Disparities in access to cancer care are more frequently seen among racial/ethnic minorities, uninsured patients, and those with low socioeconomic status. A provision in the Affordable Care Act called for expansion of Medicaid eligibility in order to cover more low-income Americans. In this study, we evaluate the impact of Medicaid expansion in 2-year mortality among metastatic BC patients according to race. Methods: Women (aged 40-64) diagnosed with metastatic BC (stage IV de novo) between 01/01/2010 and 12/31/2015 and residing in states that underwent Medicaid expansion in 01/2014 were identified in the National Cancer Database. For comparison purposes, 2010-2013 was considered the pre-expansion period and 2014-2015 the post-expansion period. We calculated 2-year mortality difference-in-difference (DID) estimates between White and non-White patients using multivariable linear regression models. Results are presented as adjusted differences (in % points) between groups in the pre- and post-expansion periods and as adjusted DID with 95%CI. Covariates included age, comorbidity, BC subtype, insurance type, transfer of care, distance to hospital, region, residence area, education, income quartile, facility type and facility volume. In addition, overall survival (OS) was evaluated in pre- and post-expansion periods via Kaplan-Meier method and Cox proportional hazards models; results are presented as 2-year OS estimates, hazard ratios (HRs), and 95% CIs. Results: Among 7,675 patients included, 4,942 were diagnosed in the pre- and 2,733 in the post-expansion period. We observed a reduction in 2-year mortality rates in both groups according to Medicaid expansion. Among Whites 2-year mortality decreased from 42.5% to 38.7% and among non-Whites from 45.4% to 36.4%, resulting in an adjusted DID of -5.2% (95%CI -9.8 to -0.6, p = 0.027). A greater reduction in 2-year mortality was observed among non-Whites in a sub-analysis of patients who resided in the poorest quartile (n = 1372), with an adjusted DID of -14.6% (95%CI -24.8 to -4.4, p = 0.005). In the multivariable Cox model, during the pre-expansion period there was an increased risk of death for non-Whites compared to Whites (HR 1.14, 95% CI 1.03 to 1.26, P = 0.04), however no differences were seen in the post-expansion period between the two groups (HR 0.93, 95% CI 0.80 to 1.07, P = 0.31). Conclusions: Medicaid expansion reduced racial disparities by decreasing the 2-year mortality of non-White patients with metastatic breast cancer and reducing the gap when compared to Whites. These results highlight the positive impact of policies aimed at improving equity and increasing access to health care.

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Retrospective Study about the Prevalence of (TILs) Tumor Infiltrating Lymphocytes in Non-Metastatic Triple Negative Breast Cancer Patients and its Prognostic Value

QJM ◽

10.1093/qjmed/hcab103.003 ◽

2021 ◽

Vol 114 (Supplement_1) ◽

Author(s):

Hesham Ahmed ElGhazaly ◽

Manal Mohamed El-Mahdy ◽

Azza Mohamed Adel ◽

Nermeen Mostafa ◽

Aya Magdy Kamal Ali

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Retrospective Study ◽

Triple Negative Breast Cancer ◽

Prognostic Value ◽

Triple Negative ◽

Free Survival ◽

Female Patients ◽

Risk Of Death ◽

Reduced Risk

Abstract Background TNBC comprises a distinct disease entity with a unique microenvironment of TILs, the immunogenic potential of TNBC is derived from its genetic instability and high mutation rate. Tumors from patients with TNBC are more likely than tumors from patients with other subtypes to exhibit chromosomal instability and potential mutations. Objectives The study aims to evaluate the prevalence of CD8+ TILs biomarker by IHC in triple negative breast cancer and its prognostic value. TILs are an important prognostic value for the response of patient to chemotherapy the greater number of TILS is associated with higher probability of response to chemotherapy also decrease recurrence. TILS in triple negative breast cancer suggest a likely option for immunotherapy in this disease. Patients and Methods This is a retrospective study, which was carried on 30 female patients, Clinical data and paraffin wax block of female patients with triple negative breast cancer are to be collected from the breast cancer unit, department of clinical Oncology and Nuclear medicine Ain Shams university and Matarya teaching hospital. Results Several large systematic reviews and meta-analyses have confirmed that high levels of TILs are associated with better disease free survival and overall survival only in triple negative and HER2 positive subtypes, with no significant benefit seen in estrogen receptor positive breast carcinoma. In the Breast International Group (BIG) 02-98 trial shows that for every 10% increase in the intertumoral TILs there was a 17% reduced risk of relapse, and 27% reduced risk of death regardless of chemotherapy type. Also in eastern cooperative oncology group trial (ECOG) 2197, and 1199 showed that for every 10% increase in TILs, a 14% reduction of risk of recurrence, and 19% reduction in risk of death were observed. Conclusion Our study showed that All our patients (100%) were positive for CD8+, with a minimum range of 1% and a maximum range of 60%, most of the patients (20 patients) had CD8% between (10% to 20%). High levels of CD8 + TILs are good prognostic indicators in TNBC. our study showed that there were associations of CD8+ TILs infiltrate status with longer progression free survival and better overall survival in triple-negative breast cancer, but were not statistically significant probably due to our small sample size.

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Trends in Survival Over the Past Two Decades Among White and Black Patients With Newly Diagnosed Stage IV Breast Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2007.14.1168 ◽

2008 ◽

Vol 26 (30) ◽

pp. 4891-4898 ◽

Cited By ~ 132

Author(s):

Shaheenah Dawood ◽

Kristine Broglio ◽

Ana M. Gonzalez-Angulo ◽

Aman U. Buzdar ◽

Gabriel N. Hortobagyi ◽

...

Keyword(s):

Breast Cancer ◽

Stage Iv ◽

The United States ◽

Breast Cancer Specific Survival ◽

Newly Diagnosed ◽

Cancer Specific Survival ◽

Risk Of Death ◽

Black Patients ◽

Stage Iv Breast Cancer ◽

White Patients

Purpose Overall, breast cancer mortality has been declining in the United States, but survival studies of patients with stage IV disease are limited. The aim of this study was to evaluate trends in and factors affecting survival in a large population-based cohort of patients with newly diagnosed stage IV breast cancer. Patients and Methods We searched the Surveillance, Epidemiology, and End Results registry to identify female patients with stage IV breast cancer diagnosed between 1988 and 2003. Patients were divided into three groups according to year of diagnosis (1988 to 1993, 1994 to 1998, and 1999 to 2003). Survival outcomes were estimated by the Kaplan-Meier method, and Cox models were fit to determine the characteristics independently associated with survival. Results We identified 15,438 patients. Median age was 62 years. Median follow-up was 16 months, 18 months, and 11 months in periods 1988 to 1993, 1994 to 1998, and 1999 to 2003, respectively. Median breast cancer–specific survival was 23 months. In the multivariate model, earlier year of diagnosis, grade 3 disease, increasing age, being unmarried, hormone receptor–negative disease, and no surgery were all independently associated with worse overall and breast cancer–specific survival. With each successive year of diagnosis, black patients had an increasingly greater risk of death compared with white patients (hazard ratio, 1.03; 95% CI, 1.00 to 1.06; P = .031). Conclusion The survival of patients with newly diagnosed stage IV breast cancer has modestly improved over time, but these data suggest that the disparity in survival between black and white patients has increased.

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