Purpose Recent studies suggest that tumor-infiltrating lymphocytes (TILs) are associated with disease-free (DFS) and overall survival (OS) in operable triple-negative breast cancer (TNBC). We seek to validate the prognostic impact of TILs in primary TNBCs in two adjuvant phase III trials conducted by the Eastern Cooperative Oncology Group (ECOG). Patients and methods Full-face hematoxylin and eosin–stained sections of 506 tumors from ECOG trials E2197 and E1199 were evaluated for density of TILs in intraepithelial (iTILs) and stromal compartments (sTILs). Patient cases of TNBC from E2197 and E1199 were randomly selected based on availability of sections. For the primary end point of DFS, association with TIL scores was determined by fitting proportional hazards models stratified on study. Secondary end points were OS and distant recurrence–free interval (DRFI). Reporting recommendations for tumor marker prognostic studies criteria were followed, and all analyses were prespecified. Results The majority of 481 evaluable cancers had TILs (sTILs, 80%; iTILs, 15%). With a median follow-up of 10.6 years, higher sTIL scores were associated with better prognosis; for every 10% increase in sTILs, a 14% reduction of risk of recurrence or death (P = .02), 18% reduction of risk of distant recurrence (P = .04), and 19% reduction of risk of death (P = .01) were observed. Multivariable analysis confirmed sTILs to be an independent prognostic marker of DFS, DRFI, and OS. Conclusion In two national randomized clinical trials using contemporary adjuvant chemotherapy, we confirm that stromal lymphocytic infiltration constitutes a robust prognostic factor in TNBCs. Studies assessing outcomes and therapeutic efficacies should consider stratification for this parameter.

Prognostic Value of Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancers From Two Phase III Randomized Adjuvant Breast Cancer Trials: ECOG 2197 and ECOG 1199

Background National Central Cancer Registry of China (NCCRC) updated nationwide cancer statistics using population-based cancer registry data in 2014 collected from all available cancer registries. Methods In 2017, 449 cancer registries submitted cancer registry data in 2014, among which 339 registries' data met the criteria of quality control and were included in analysis. These cancer registries covered 288,243,347 population, accounting for about 21.07% of the national population in 2014. Numbers of nationwide new cancer cases and deaths were estimated using calculated incidence and mortality rates and corresponding national population stratified by area, sex, age group and cancer type. The world Segi's population was applied for age-standardized rates. Results A total of 3,804,000 new cancer cases were diagnosed, the crude incidence rate was 278.07/100,000 (301.67/100,000 in males, 253.29/100,000 in females) and the age-standardized incidence rate by world standard population (ASIRW) was 186.53/100,000. Calculated age-standardized incidence rate was higher in urban areas than in rural areas (191.6/100,000 vs. 179.2/100,000). South China had the highest cancer incidence rate while Southwest China had the lowest incidence rate. Cancer incidence rate was higher in female for population between 20 to 54 years but was higher in male for population younger than 20 years or over 54 years. A total of 2,296,000 cancer deaths were reported, the crude mortality rate was 167.89/100,000 (207.24/100,000 in males, 126.54/100,000 in females) and the age-standardized mortality rate by world standard population (ASMRW) was 106.09/100,000. Calculated age-standardized mortality rate was higher in rural areas than in urban areas (110.3/100,000 vs. 102.5/100,000). East China had the highest cancer mortality rate while North China had the lowest mortality rate. The mortality rate in male was higher than that in female. Common cancer types and major causes of cancer death differed between age group and sex. Conclusions Heavy cancer burden and its disparities between area, sex and age group pose a major challenge to public health in China. Nationwide cancer registry plays a crucial role in cancer prevention and control.

/pdf/cancer-incidence-and-mortality-in-china-2014-4e2woagh1c.pdf

Cancer incidence and mortality in China, 2014.

Cancer is the leading cause of human deaths in the world and produces serious economic burdens. On September 12, 2018, the academic journal A Cancer Journal for Clinicians published an article about the latest statistics of cancers worldwide, which provided a status report on the global burden of 36 cancers in 185 countries worldwide. Cancer has also become a serious public health problem in China and caused more and more attention of the government and people in recent years. This review analyzes the incidence, mortality and prevalent trend of cancers in China, discusses the reasons behind this status, and reviews the potential countermeasures for cancer prevention and control in China.

Analysis of status and countermeasures of cancer incidence and mortality in China.

Background Breast cancer is the most commonly diagnosed cancer and leading cause of cancer death among women worldwide but has patterns and trends which vary in different countries. This study aimed to evaluate the global patterns of breast cancer incidence and mortality and analyze its temporal trends for breast cancer prevention and control. Methods Breast cancer incidence and mortality data in 2020 were obtained from the GLOBOCAN online database. Continued data from the Cancer Incidence in Five Continents Time Trends, the International Agency for Research on cancer mortality and China National Central Cancer Registry were used to analyze the time trends from 2000 to 2015 through Joinpoint regression, and annual average percent changes of breast cancer incidence and mortality were calculated. Association between Human Development Index and breast cancer incidence and mortality were estimated by linear regression. Results There were approximately 2.3 million new breast cancer cases and 685,000 breast cancer deaths worldwide in 2020. Its incidence and mortality varied among countries, with the age-standardized incidence ranging from the highest of 112.3 per 100,000 population in Belgium to the lowest of 35.8 per 100,000 population in Iran, and the age-standardized mortality from the highest of 41.0 per 100,000 population in Fiji to the lowest of 6.4 per 100,000 population in South Korea. The peak age of breast cancer in some Asian and African countries were over 10 years earlier than in European or American countries. As for the trends of breast cancer, the age-standardized incidence rates significantly increased in China and South Korea but decreased in the United States of America (USA) during 2000-2012. Meanwhile, the age-standardized mortality rates significantly increased in China and South Korea but decreased in the United Kingdom, the USA, and Australia during 2000 and 2015. Conclusions The global burden of breast cancer is rising fast and varies greatly among countries. The incidence and mortality rates of breast cancer increased rapidly in China and South Korea but decreased in the USA. Increased health awareness, effective prevention strategies, and improved access to medical treatment are extremely important to curb the snowballing breast cancer burden, especially in the most affected countries.

Global patterns of breast cancer incidence and mortality: A population-based cancer registry data analysis from 2000 to 2020

Rapid growth in nanotechnology toward the development of nanomedicine agents holds massive promise to improve therapeutic approaches against cancer. Nanomedicine products represent an opportunity to achieve sophisticated targeting strategies and multifunctionality. Nowadays, nanoparticles (NPs) have multiple applications in different branches of science. In recent years, NPs have repetitively been reported to play a significant role in modern medicine. They have been analyzed for different clinical applications, such as drug carriers, gene delivery to tumors, and contrast agents in imaging. A wide range of nanomaterials based on organic, inorganic, lipid, or glycan compounds, as well as on synthetic polymers has been utilized for the development and improvement of new cancer therapeutics. In this study, we discuss the role of NPs in treating cancer among different drug delivery methods for cancer therapy.

Nanoparticles and cancer therapy: Perspectives for application of nanoparticles in the treatment of cancers.

Characteristics of breast cancer in Central China, literature review and comparison with USA

BACKGROUND Topoisomerase 2 alpha (TOP2A) is a key enzyme in DNA replication and a target of various cytotoxic agents including anthracyclines. Previous studies evaluating the predictive and prognostic values of TOP2A in breast cancer are contradictory, likely secondary to the use of both different detection methods and different cutoff thresholds for positive status. Our own studies have previously confirmed the advantages of quantum dot-based nanotechnology for quantitative analysis of biomarkers relative to conventional immunohistochemistry (IHC). This study was designed to 1) assess the expression of TOP2A, 2) investigate the relationship between TOP2A expression and major clinical pathological parameters, and 3) evaluate the prognostic value of TOP2A by quantum dot-based immunofluorescent imaging and quantitative analytical system (QD-IIQAS) in triple-negative breast cancer (TNBC). PATIENTS AND METHODS TOP2A expression in 145 TNBC specimens was detected using IHC and QD-IIQAS, and a comparative analysis of the two methods was conducted, including an exploration of the relationship between TOP2A expression and major clinical pathological parameters in TNBC. The prognostic value of TOP2A in TNBC was assessed. RESULTS A similar antigen localization, a high correlation of staining rates (r=0.79), and a high agreement of measurements (κ=0.763) of TOP2A expression in TNBC were found by QD-IIQAS and conventional IHC (cutoff: 45.0 and 0.45, respectively). TOP2A was significantly higher in larger tumors (P=0.002), higher grade tumors (P=0.005), and lymph node positive patients (P<0.001). The 5-year disease-free survival (5-DFS) of the high and low TOP2A subgroups was significantly different for both QD-IIQAS and IHC (P<0.001, log-rank test for both). TOP2A expression was an independent predictor of survival in TNBC (P=0.001). CONCLUSION QD-IIQAS was an easy and accurate method for detecting and assessing TOP2A. The TOP2A expression was an independent prognostic indicator of 5-DFS in TNBC. Our study provides a good foundation for future studies exploring the relationship between TOP2A expression and response to anthracyclines.

/pdf/quantum-dot-based-immunofluorescent-imaging-and-quantitative-3d984is50t.pdf

Quantum dot-based immunofluorescent imaging and quantitative detection of TOP2A and prognostic value in triple-negative breast cancer

Ki67 has potential prognostic and predictive values for breast cancer patients, and has become an important biomarker in routine clinical practice. The aims of the present study were to investigate the distribution of Ki67 expression and its correlation with other clinicopathological parameters in central China. In total, 1,259 patients with newly-diagnosed invasive breast cancer were included in the present study. The clinical information was obtained from the electronic medical records. The expression levels of Ki67, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) were detected by immunohistochemical analysis. The associations between Ki67 scores and other prognostic factors were evaluated as continuous and categorical variables. The mean value of the Ki67 scores of all patients was 31%. In total, ~36% (456/1,259) of the patients demonstrated a low expression of Ki67. A statistically significant correlation was identified between the mean Ki67 scores and the lymph node status, tumor grade, ER, PR and HER2 status, and clinical stage or molecular subtypes (all P 14%) and low (≤14%) level groups, the χ2 test was used to verify these results. The Ki67 scores demonstrated no statistically significant differences between the HER2-positive (non-luminal) and three negative subtypes, with the exception of patients with a tumor size of >2 cm (P=0.02). In conclusion, the results revealed the presence of significant correlations between Ki67 and other clinicopathological parameters.

/pdf/associations-and-indications-of-ki67-expression-with-oybixlyonm.pdf

Associations and indications of Ki67 expression with clinicopathological parameters and molecular subtypes in invasive breast cancer: A population-based study

Triple-negative breast cancer (TNBC) is a unique breast cancer subtype with high heterogeneity and poor prognosis. Currently, the treatment effect of TNBC has reached a bottleneck, rendering new breakthroughs difficult. Cancer invasion is not an entirely cell-autonomous process, requiring the cells to transmigrate across the surrounding extracellular matrix (ECM) barriers. Developing a new system that integrates key constituents in the tumor microenvironment with pivotal cancer cell molecules is essential for the in-depth investigation of the mechanism of invasion in TNBC. We describe a computer-aided algorithm developed using quantum dot (QD)-based multiplex molecular imaging of TNBC tissues. We performed in situ simultaneous imaging and quantitative detection of epidermal growth factor receptor (EGFR), expressed in the TNBC cell membrane, and collagen IV, the major ECM constituent; calculated the EGFR/collagen IV ratio; and investigated the prognostic value of the EGFR/collagen IV ratio in TNBC. We simultaneously imaged and quantitatively detected EGFR and collagen IV in the TNBC samples. In all patients, quantitative determination showed a statistically significant negative correlation between EGFR and collagen IV. The 5-year disease-free survival (5-DFS) of the high and low EGFR/collagen IV ratio subgroups was significantly different. The EGFR/collagen IV ratio was predictive and was an independent prognostic indicator in TNBC. Compared with EGFR expression, the EGFR/collagen IV ratio had a greater prognostic value for 5-DFS. Our findings open up a new avenue for predicting the clinical outcome in TNBC from the perspective of integrating molecules expressed in both cancer cells and the ECM.

Quantum dot-based in situ simultaneous molecular imaging and quantitative analysis of EGFR and collagen IV and identification of their prognostic value in triple-negative breast cancer.

Fibroadenomas are a type of benign tumor that occur in young women below the age of 35 years old. The tumors are the second most common type of tumor after fibrocystic disease. The chance of carcinoma arising in a fibroadenoma is extremely low. To date, <130 such cases have been reported. Previous studies have reported that fibroadenomas can evolve into a number of different types of malignancy. The present study is the first to describe a case of bilateral primary breast cancer with a unilateral invasive ductal carcinoma within a fibroadenoma. The current study presents a case of a 48-year-old female who presented with 2 stiff lumps on bilateral breasts, diagnosed as bilateral breast carcinoma, with a unilateral invasive ductal carcinoma within a fibroadenoma in the right breast. The patient underwent a bilateral mastectomy and subsequently received 4 cycles of chemotherapy (epirubicin, 60 mg/m2 and cyclophosphamide, 600 mg/m2) every 21 days, followed by 4 cycles of docetaxel chemotherapy (100 mg/m2) every 21 days. The patient then received maintenance endocrine therapy (tamoxifen, 20 mg, twice daily) for 19 months. The patient was followed up every 3 months, and at the last follow-up examination in May 2015, the patient exhibited no signs of recurrence.

/pdf/bilateral-breast-cancer-with-a-unilateral-carcinoma-within-a-4h828qoxoi.pdf

Hongmei Zheng

Papers

Characteristics of breast cancer in Central China, literature review and comparison with USA

Quantum dot-based immunofluorescent imaging and quantitative detection of TOP2A and prognostic value in triple-negative breast cancer

Associations and indications of Ki67 expression with clinicopathological parameters and molecular subtypes in invasive breast cancer: A population-based study

Quantum dot-based in situ simultaneous molecular imaging and quantitative analysis of EGFR and collagen IV and identification of their prognostic value in triple-negative breast cancer.

Bilateral breast cancer with a unilateral carcinoma within a fibroadenoma: A case report.