Biological Characteristics Of Breast Cancer Research Articles

Quantitative Analysis of Shear Wave Elastography and US-Guided Diffuse Optical Tomography for Evaluating Biological Characteristics of Breast Cancer

Shear Wave Elastography (SWE) and Ultrasound-guided Diffuse Optical Tomography (US-guided DOT) demonstrate promise in distinguishing between benign and malignant breast lesions. This study aims to assess the feasibility and correlation of SWE and US-guided DOT in evaluating the biological characteristics of breast cancer. A cohort of 235 breast cancer patients with 238 lesions, scheduled for surgery within one to three days, underwent B-mode ultrasound (US), US-guided DOT, and SWE. Parameters such as Total Hemoglobin Concentration (THC), Maximal Elasticity (Emax), Mean Elasticity (Emean), Standard Deviation of Elasticity (Esd), and Area Ratiowere measured. Correlation with post-surgical pathology reports was examined to explore associations between THC, SWE Parameters, and pathology characteristics. Lesions in patient groups with ER-, PR-, HER2+, high Ki67, LVI+, and ALN+exhibited higher THC, Emax, and Esd compared to groups with ER+, PR+, HER2-, low Ki67, LVI-, and ALN-. The increase was seen in all grades of IDC-I to -III. THC significantly correlated with Smax (r=0.340, P<0.001), Emax (r=0.339, P<0.001), Emean (r=0.201, P=0.003), and Esd (r=0.313, P<0.001). US-guided DOT and SWE prove valuable for the quantitative assessment of breast cancer's biological characteristics, with THC positively correlated with Emax, Emean, and Esd.

The mechanism of lapatinib and its application in breast cancer

This paper aims to study the synthetic route, mechanism of action and application of lapatinib in breast cancer. As a common malignant tumor, breast cancer poses a serious threat to the life and health of patients. As an effective targeted drug, lapatinib is significant in treating breast cancer. Its pharmacological effects can block the growth and metastasis of tumor cells by inhibiting specific signaling pathways and affect cancer cells metabolism and drug efficacy. Its molecular mechanism is mainly through targeting the epidermal growth factor receptor (EGFR) to inhibit the proliferation and survival of tumor cells. Studies on lapatinibs drug metabolism and pharmacodynamics also described its metabolism and therapeutic effect in vivo. Secondly, the pathophysiology of breast cancer was summarized, including the pathogenesis, clinical manifestations, and molecular biological characteristics of breast cancer. The therapeutic effect, application, efficacy evaluation, and adverse reaction management of lapatinib were analyzed for the application of lapatinib in the treatment of breast cancer. Moreover, the existing lapatinib synthetic routes were described. Lapatinib has a substantial treatment influence and may effectively decrease harmful reactions when used to treat breast cancer. Nevertheless, additional study is required to ascertain its optimal application and possible mechanism of action in breast cancer treatment.

Correlation between connexin 43 expression in circulating tumor cells and biological characteristics of breast cancer

BackgroundConnexin 43 (Cx43) has been closely linked to the occurrence and progression of breast cancer. Distant metastasis of breast cancer is aided by the epithelial-mesenchymal transition of circulating tumor cells (CTCs). However, the impact of Cx43 expression on CTCs and the extent of its role in the disease remain unclear. MethodsWe determined CTCs in 156 patients, who had breast cancer with a disease course of two or more years. We also measured the expression of Cx43 in the CTCs. The CTCs were detected in the blood of 139 of these patients. These 139 patients were divided into two groups: the Cx43 group and the non-Cx43 group based on their Cx43 expression. ResultsOverall, Cx43 expression was found in 83 of the 139 patients (59.7%, 83/139 cases). The two groups significantly differed in terms of the number of mixed biphenotypic type CTCs and the total number of CTCs (P < 0.05). There were significant correlations between Cx43 expression and Ki67 expression, tumor size, lymph node metastasis, and TNM stage (P < 0.05 for all). The data suggested that patients with Cx43 expression had a higher risk of distant metastasis and had later-stage disease. The difference in Cx43 expression between patients with and without epidermal growth factor receptor 2 (Her2) overexpression was statistically significant (P < 0.05). The difference in disease-free survival (DFS) between the two groups was statistically significant (P = 0.03), and the Cx43 group had a shorter duration of DFS. Univariate Cox regression analysis revealed that Cx43 expression, Her2 expression, and tumor size were significantly correlated with DFS (P = 0.03, 0.0023, and 0.01, respectively). ConclusionCx43 expression in the CTCs of patients with breast cancer is a cancer-promoting factor.

Evolution and clinical significance of HER2-low status after neoadjuvant therapy for breast cancer.

The emergence of HER2 antibody-drug conjugates provides new treatment decisions for breast cancer patients, especially those with HER2-low expression. In order to explore the biological characteristics of breast cancer with HER2-low expression, the HER2-low category in primary breast cancer and residual tumor after neoadjuvant therapy was investigated to reflect the evolution of HER2 expression. HER2 was assessed according to the latest ASCO/CAP guidelines. The cut-off value for staining of HER2-positive cells was >10%. HER2-negative cases were divided into HER2-low (IHC=1+/2+ and no ISH amplification) and HER2-zero (IHC-0), and the clinicopathological characteristics of the cases were collected. This study included 1140 patients with invasive breast cancer who received preoperative neoadjuvant therapy from 2018 to 2021, of which 365 patients achieved pCR and 775 were non-pCR. In the non-pCR cohort, HER2-low cases accounted for 59.61% of primary tumors and 55.36% of residual tumors. Among HER2-negative cases, HR-positive tumors had a higher incidence of low HER2 expression compared with triple-negative tumors (80.27% vs 60.00% in primary tumors and 72.68% vs 50.77% in residual tumors). The inconsistency rate of HER2 expression was 21.42%, mainly manifested as the conversion of HER2-low cases to HER2-zero (10.19%) and the conversion of HER2-zero to HER2-low (6.45%). Among the HER2-negative cases in the primary tumor, the HER2 discordance rate of HR-positive cases was lower than that of triple-negative cases (23.34% VS 36.92%). This difference was mainly caused by the case switching from HER2-low to HER2-zero. Compared with HER2-zero cases, there were statistically significant differences in RCB grade, MP grade and the number of metastatic lymph nodes in HER2-low cases. Patients with low HER2 expression had a lower pathological response rate and a higher number of metastatic lymph nodes. HER2-low breast cancer is highly unstable during disease evolution and has certain biological characteristics. HER2-low breast cancer is not only correlated with positive HR, but also has a certain correlation with positive AR. Re-detection of HER2 in breast cancer after neoadjuvant therapy may lead to new treatment opportunities for a certain proportion of patients.

Circular RNA_0006014 promotes breast cancer progression through sponging miR-885-3p to regulate NTRK2 and PIK3/AKT pathway.

Breast cancer is the most common cancer in women worldwide. Numerous reports have demonstrated that circRNAs play an essential role in regulating the biological characteristics of breast cancer. However, there are currently no reports regarding the role of hsa_circ_0006014 in breast cancer. In this study, qRT-PCR was used to detect the expression of hsa_circ_0006014 and related genes. MTT, colony formation and Transwell assays were used to explore the potential biological functions of hsa_circ_0006014 in breast cancer cells. Western blotting was used to explore the potential molecular mechanisms involving hsa_circ_0006014. In vivo experiments were used to evaluate the influence of hsa_circ_0006014 on animal tumors. In this study, we found higher expression of hsa_circ_0006014 in breast tumor samples than in matched adjacent normal samples, and its expression was positively correlated with histological grade (grade iii). Phenotypically, hsa_circ_0006014 promoted the proliferation of MDA-MB-231 and MCF-7 breast cancer cells. Mechanistically, there were confirmed binding sites between hsa_circ_0006014 and miR-885-3p, and hsa_circ_0006014 promoted breast cancer cell proliferation partially by sponging miR-885-3p and influenced CDK2/CCNE1 and CDK4/6/CCND1. Furthermore, we found that hsa_circ_0006014 regulated NTRK2 through miR-885-3p to modulate the PIK3/AKT signaling pathway. Our results demonstrated that hsa_circ_0006014 promotes breast cancer progression by sponging miR-885-3p to regulate the NTRK2/PIK3CA/AKT axis.

Circulating microRNAs as indicators in the prediction of neoadjuvant chemotherapy response in luminal B breast cancer.

PurposeCirculating microRNAs (miRNAs) have been indicated as predictive biomarker for the response to neoadjuvant chemotherapy (NAC) and the prognosis of breast cancer (BC); however, to date the conclusions have been controversial. The biological characteristics of BC were affected by molecular subtypes. Hence, we aimed to investigate the predictive effect of miRNAs on NAC response in luminal B BC patients.MethodsThirty‐seven luminal B BC patient under NAC were prospectively enrolled in this study. Based on their clinical, pathological, and comprehensive response, the patients were defined as responder or non‐responders, respectively. Circulating miRNAs were isolated from blood samples before and at the middle of NAC, and candidate miRNAs (miR‐34a‐5p, miR‐125b‐5p, miR‐210, miR‐222, miR‐375, miR‐718, miR‐4516, and let‐7g) were analyzed by quantitative real‐time polymerase chain reaction (PCR). In addition, the association between miRNAs and disease‐free survival (DFS) was examined.ResultsmiR‐718, miR‐4516, miR‐210, and miR‐125b‐5p were found to be specific miRNAs associated with chemo‐sensitivity of luminal B HER2 negative patients (n = 24). In the luminal B HER2 positive cohort (n = 13), dynamics of miR‐222 and let‐7g correlated with pathological response. Treatment‐induced increase in miR‐34a‐5p in the responders except who reached pathologic complete response (pCR) was consistently identified across all luminal B patients and its two subgroups. Finally, after adjustments for Neo‐Bioscore, patients with increased levels of miR‐125b‐5p during NAC had a worse DFS than those with decreased levels (HR = 5.86, 95% CI = 1.39–24.62, p = 0.016).ConclusionSpecific circulating miRNAs were identified as predictive markers for NAC response and prognosis in luminal B BC. The underlying mechanism needs further studies.

Clinical and Biological Characteristics of Breast Cancer in Women with Mammary Paget's Disease: A Retrospective Study of 36 cases

Clinical and Biological Characteristics of Breast Cancer in Women with Mammary Paget's Disease: A Retrospective Study of 36 cases

Shear-Wave Elastography of the Breast: Added Value of a Quality Map in Diagnosis and Prediction of the Biological Characteristics of Breast Cancer.

ObjectiveTo determine the added value of a shear-wave elastography (SWE) quality map (QM) in the diagnosis of breast lesions and in predicting the biological characteristics of invasive breast cancer.Materials and MethodsBetween January 2016 and February 2019, this study included 368 women with 368 pathologically proven breast lesions, which appeared as poor-quality regions in the QM of SWE. To measure shear-wave velocity (SWV), seven regions of interest were placed in each lesion with and without QM guidance. Under QM guidance, poor-quality areas were avoided. Diagnostic performance was calculated for mean SWV (SWVmean), max SWV (SWVmax), and standard deviation (SD) with QM guidance (SWVmean + QM, SWVmax + QM, and SD + QM, respectively) and without QM guidance (SWVmean − QM, SWVmax − QM, and SD − QM, respectively). For invasive cancers, the relationship between SWV findings and biological characteristics was investigated with and without QM guidance.ResultsOf the 368 women (mean age, 47 years; SD, 10.8 years) enrolled, 159 had benign breast lesions and 209 had malignant breast lesions. SWVmean + QM (3.6 ± 1.39 m/s) and SD + QM (1.02 ± 0.84) were significantly different from SWVmean − QM (3.29 ± 1.22 m/s) and SD − QM (1.46 ± 1.06), respectively (all p < 0.001). For differential diagnosis of breast lesions, the sensitivity and areas under the receiver operating characteristic curve (AUC) of SWVmean + QM (sensitivity: 89%; AUC: 0.932) were better than those of SWVmean − QM (sensitivity, 84.2%; AUC, 0.912) (all p < 0.05). There was no significant difference in sensitivity and specificity between SD + QM and SD − QM (all p = 1.000). Among the biological characteristics of invasive cancers, lymphovascular involvement, axillary lymph node metastasis, negative estrogen receptor status, negative progesterone receptor status, positive human epidermal growth factor receptor status, and aggressive molecular subtypes showed higher SWVmean + QM (all p < 0.05), while only lymphovascular involvement showed higher SWVmean − QM (p = 0.036).ConclusionThe use of QM in SWE might improve the diagnostic performance for breast lesions and facilitate prediction of the biological characteristics of invasive breast cancers.

Research Advances on Effect of Adipose-derived Stem Cells on Biological Characteristics of Breast Cancer

Research Advances on Effect of Adipose-derived Stem Cells on Biological Characteristics of Breast Cancer

Abstract P1-17-07: Cancer management and outcome of very young non-pregnant patients with breast cancer diagnosed at 40 years or younger– GBG 29

Abstract Introduction Breast cancer diagnosed in young women who are 40 years (yrs) or younger is a relatively rare disease. However, it represents the most common cause of cancer-related deaths in this age-group. Furthermore, young age at diagnosis is associated with an increased risk of recurrence and worse survival. To date, general concepts concerning oncological cancer management should be driven by clinicopathological tumor characteristics and should adhere to standardized protocols for patients in general, but little is known about the oncological cancer treatment and outcome of this very young women in today's clinical practice. Patients and Methods The breast cancer in pregnancy registry study (BCP/GBG29/BIG 03-02) is a multicenter, international, observational study. BCP was established to investigate the oncological management and outcome of breast cancer in pregnancy. Since 2014 non-pregnant patients who are 40 yrs or younger are eligible if diagnosed with histological confirmed invasive breast cancer, independent of the type of treatment as control cohort. All patients received oncological treatment according to local standards. In this study the following endpoints will be analyzed descriptively for the young non-pregnant women cohort: breast cancer staging at diagnosis, biological characteristics of breast cancer at diagnosis, diagnostic procedures, treatment modalities, toxicity, pathological complete response after neoadjuvant chemotherapy, disease-free survival and overall survival. Results From February 2014 until June 2018, 969 non-pregnant patients ≤40 yrs have been registered. The median age at diagnosis was 35 yrs (range 19-40). Overall, 90.1% of patients had a stage T1-2 at diagnosis and 67.1% of patients had negative lymph nodes. 86.7% of tumors were invasive ductal carcinomas and 4.1% lobular carcinomas. Grading (G) 3 was reported in 55.5%. 26.6% of tumors were luminal A-like (ER- and/or PgR-positive, HER2-negative, G1-2), 40.0% luminal B-like (ER- and/or PgR-positive, HER2-negative, G3 or ER- and/or PgR-positive, HER2-positive, any G), 7.7% HER2 positive non-luminal-like, and 25.7% triple negative breast cancers. 3.8% of young non-pregnant patients had metastatic disease at primary diagnosis. Conclusion This registry comprises a large cohort of young non-pregnant patients with breast cancer diagnosed at the age of 40 yrs or younger and provides important data about a modern breast cancer treatment as well as oncological outcome in this setting of young women. Further results including oncological management, toxicity, and survival will be presented at the meeting. Citation Format: Seiler S, Schmatloch S, Reinisch M, Neunhöffer T, Schmidt M, Bechtner C, Marmé F, Wagner M, Möbus V, Reimer T, Kleine-Tebbe A, Sinn B, Stickeler E, Untch M, Janni W, Seither F, Loibl S. Cancer management and outcome of very young non-pregnant patients with breast cancer diagnosed at 40 years or younger– GBG 29 [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-17-07.

Prediction of biological characteristics of breast cancer using dual-phase FDG PET/CT.

The aim of this study was to assess whether the retention index (RI) determined using dual-phase 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) reflects the malignant features of breast cancer. A total of 1,523 patients with breast cancer were retrospectively evaluated. PET/CT scans were performed at 1h and 2h after FDG administration before treatment. The maximum standardized uptake value (SUVmax) at both time points (SUVmax1 and SUVmax2) in the primary tumour and RI were calculated. Primary tumour tissues were evaluated in terms of biological features, such as histology, nuclear grade, lymphovascular invasion and molecular subtype. Of the 1,523 patients, 463 (30.4%) had luminal A-like, 661 (43.4%) had luminal B-like, 229 (15.0%) had human epidermal growth factor receptor 2-positive (HER2-positive), and 157 (10.3%) triple-negative breast cancer. The median SUVmax1, SUVmax2 and RI values were 2.2, 2.3 and 2.6%, respectively. These metabolic parameters were correlated with tumour size, nodal metastasis, histology, nuclear grade, lymphovascular invasion, and molecular subtype (all P < 0.001). The median RI values were 0% in luminal A-like, 5.3% in luminal B-like, 6.9% in HER2-positive, and 11.4% in triple-negative breast cancer. RI was associated with malignant features when the tumour accumulated a significant amount of FDG. In a subanalysis of patients with tumours of stages T2 to T4, RI was correlated with nodal metastasis, histology, nuclear grade, and molecular subtype (luminal A-like 4.8%, luminal B-like 12.3%, HER2-positive 15.8%, and triple-negative 16.3%). RI determined using delayed-phase FDG PET/CT is associated with malignant features in breast cancers with significant FDG uptake. Dual-phase imaging was helpful in distinguishing luminal A-like breast cancer from luminal B-like, HER2-positive, and triple-negative breast cancers.

Correlation between the maximum elastic modulus(Emax) shear-wave elastography and immunohistochemical profiles in breast cancer

Objective To investigate the correlation between the maximum elastic modulus(Emax) of breast cancer obtained by shear-wave elastography (SWE) and immunohistochemical profiles. Methods One hundred and sixty patients with 171 pathologically proven breast lesions were included in this study. All of them underwent conventional ultrasound and SWE examination before surgery. The Emax and maximum diameter were obtained. Histologic grade, immunohistochemical profiles ER, PR, HER-2, Ki-67 and molecular subtypes were recorded according to pathological results after surgery. The correlation between Emax and tumor size, histological grade, ER, PR, HER-2, Ki-67 and molecular subtypes were analyzed. Results ①There was a positive correlation between the tumor size with Emax(r=0.510, P<0.05); ②The Emax of tumors with HER-2 positive expression were higher than that with HER-2 negative expression(P<0.05), the Emax of tumors with Ki67 high expression were higher than that with Ki67 low expression (P<0.05); ③There were significant differences in Emax between different molecular subtypes(P<0.05), the Emax of HER-2 positive tumor was the highest, followed by those of Luminal B tumor, triple-negative and Luminal A tumor; ④Multiple linear regression indicated that tumor size was the strongest pathologic determinate of Emax value(P<0.05), its standardized partial regression coefficient was 0.500, and HER-2 also had significant influence on Emax value of tumor(P<0.05), the standardized partial regression coefficient was 0.237. Conclusions Some prognosis immunohistochemical feature of breast cancer showed association with the Emax. Breast cancers with higher Emax at shear-wave elastography had poor prognostic features. To some extend, the value of Emax can reflect the biological characteristics of breast cancer, SWE may provide a certain imaging basis for the prognosis of breast cancer and the choice of treatment plan. Key words: Ultrasonography; Breast Neoplasms; Elasticity imaging techniques; Immunohistochemical profiles

EARLY BREAST CANCER: THE IMPORTANCE OF THE BIOLOGICAL TUMOR SUBTYPE FOR CHOOSING SURGICAL TREATMENT TACTICS (А LITERATURE REVIEW)

Purpose: to determine the dependence of the development of local relapse depending on the chosen tactics of surgical treatment with different biological subtypes of breast cancer. Materials and methods: molecular taxonomy of breast cancer may improve the prognosis of regional regional recurrence (MPR) and has a great potential for improving decisionmaking regarding local treatment for breast cancer. The review of the world literature, reflecting prospective and retrospective studies on the biological characteristics of breast cancer, is reviewed. The studies reflect such parameters as the degree of malignancy, the age of the patients, the biological subtype of the tumor, and the treatment performed. The development of local and regional regional relapse was assessed depending on the choice of surgical treatment tactics: radical mastectomy and organ-preserving treatment + radiotherapy. The search was limited to 2001, when biological subtypes of breast cancer were identified. Prospective and retrospective studies were evaluated in patients with early operable breast cancer. Conclusions: young age, tumor malignancy, tumor node size, presence of lymphovascular invasion or lymph node involvement and unfavorable tumor subtypes such as Her2 /neu and triple-negative tumors can be considered as the main predictors of relapse in breast cancer. Tumors having a triple-negative nature have the most aggressive course, this concerns both local, regional relapse, and distant metastasis. Advances in modern neoadjuvant therapy have reduced the overall number of local relapses for all subgroups. Radiation therapy also helps to reduce the risk of local and regional recurrence. At present, there is no single-valued data on the choice of surgical treatment tactics for various biological subtypes, however effective systemic therapy as well as radiotherapy reduces the frequency of local recurrences after performing organ-preserving surgeries in unfavorable tumor subtypes and according to the results of studies, the total and disease-free survival is comparable, as and during mastectomy.

Correlation of Prognostic Factors of Invasive Lobular Carcinoma with ADC Value of DWI and SUVMax of FDG-PET.

Invasive lobular carcinoma (ILC) is the second most common kind of breast cancer. Diffusion weighted imaging (DWI) and positron emission tomography/computed tomography (PET/CT) are functional modalities for presenting the biological characteristics of breast cancer. The purpose of this article is to study the relationship between DWI or PET/CT and ILC's prognostic factors. The relationship between the apparent diffusion coefficient (ADC) values, standard uptake value (SUV)max and prognostic factors of ILC were statistically evaluated. The ADC values were lower in mass types of ILC. SUVmax was statistically higher in grade 3 and 4 background parenchymal enhancement and positive lymph node metastasis. ADC values of DWI and SUVmax of PET/CT can be helpful in the prediction of the prognosis of ILC.

Advances in the comprehensive treatment of young women patients with breast cancer

The incidence rate of young women with breast cancer is increasing. Because of distinct biological characteristics of breast cancer in young patients, it is reasonable to identify who is the best one for breast-conserving surgery. Patients with systemic chemotherapy should be fully considered about fertility requirements. In addition, endocrine therapy combined with ovarian function inhibition can improve the effect, meanwhile, there should increase the proportion of patients with targeted therapy. Key words: Breast neoplasms; Therapy

A51: Immunologic microenvironment and some molecular biological characteristics of breast cancer

The purpose of the study was to assess parameters of local cellular immunity, expression of apoptosis-controlling proteins and some other receptors in various molecular subtypes of breast cancer (BC) with different clinical course and prognosis. Materials and methods 100 BC patients aged 30–76 years (59 ± 3.4) were recruited. Tissues of tumor and peritumoral area were homogenized by MediMachine, subset contents of T, B, NK-lymphocytes were estimated by flow cytometer FACS CantoII. Percentage of lymphocytes expressing CD3, CD4, CD8, CD19, CD16/56, were counted from total amount of CD45+ lymphocytes. Sections of paraffin-embedded blocks were studied by immunohistochemical method with polyvalent HRP-DAB detection system. Staining was performed using Thermo Scientific autostainer. Tumor was considered p53-positive when >25% of tumor cell nuclei were positively stained, and bcl-2-positive when >25% of cells showed specific cytoplasmic staining. Expression of E-cadherin was assessed by the number of cells with positive membrane expression of this marker, taking into account intensity of the reaction. Expression of topoisomerase 2α and androgen receptors was assessed by the number of tumor cells with positive nuclear expression of these markers; number of stained nuclei per 100 nuclei in 3 fields of view was counted. Results Some differences characterizing tumor cells of molecular breast cancer subtypes were found. Tumor tissue contained higher amount of T-lymphocytes than blood (85.9 ± 2.36% vs 60.1 ± 4.5%, P p53 overexpression was equally often recorded in luminal B and Her2+ subtypes of BC and slightly less frequently in triple-negative subtype. Accumulation of p53 was 2 times less frequently detected in luminal A subtype in comparison with triple -negative cancer and 2.5 and 2.7 times less frequently in comparison with luminal B and Her2+ BC, respectively. Study of bcl-2 expression showed reducing the frequency of positive tumor cell staining in dependence on the receptor status of tumor: positive cases were several times less frequent in triple-negative and Her2+ subtypes in comparison with luminal A and B subtypes. Luminal A subtype was characterized by the minimal p53, topoisomerase 2 α and androgen receptor expression and maximal expression of bcl-2 and E-cadherin. Luminal B subtype showed a high expression of p53, bcl-2 and androgen receptors and moderate expression of topoisomerase 2 α and E-cadherin. High expression of topoisomerase 2 α , low expression of androgen receptors and moderate expression of E- cadherin were registered in triple-negative BC. The maximal expression of topoisomerase 2 α and p53, as well as low expression of bcl-2 and E-cadherin, was observed in Her2+ subtype. Conclusions CD8+ T-lymphocytes dominate in tumor tissue of BC. Besides, tumor tissue of luminal A BC contains more NK-cells than other subtypes. A number of differences in expression of apoptosis-controlling proteins was observed in various molecular subtypes of breast cancer. Luminal A BC was noted for the minimal p53 expression and maximal bcl-2expression. Luminal B subtype had a high p53 and bcl- 2 expression. In Her2+ BC p53 expression was maximal and bcl-2 expression was low. The described differences allow assessing molecular subtypes of breast cancer and predicting the disease course from previously unexplored perspectives.

1903 Some molecular biological characteristics of breast cancer

1903 Some molecular biological characteristics of breast cancer

TAT-ODD-p53 enhances the radiosensitivity of hypoxic breast cancer cells by inhibiting Parkin-mediated mitophagy.

Radiation therapy has an important role in the treatment of breast cancer. Dysfunction p53 and hypoxia are typical biological characteristics of breast cancer that constitute barriers to the efficacy of radiotherapy. Mitophagy plays a protective role in cellular homeostasis under hypoxic conditions, while mitophagy is inhibited by p53 in normal cells. We explored the effects of a p53 fusion protein, TAT-ODD-p53, on the radiosensitivity of hypoxic breast cancer cells both in vitro and in vivo, as well as investigating the related molecular mechanisms. We found that selective accumulation of TAT-ODD-p53 occurred under hypoxic conditions and significantly increased tumor cell radiosensitivity both in vitro and in vivo. Mitophagy had an important role in maintaining hypoxia-induced radioresistance. Mitophagy was inhibited by TAT-ODD-p53 and this inhibition was suppressed by over-expression of Parkin in hypoxic irradiated breast cancer cells. In addition, mitophagy was induced by deletion of p53, with this effect being weakened by Parkin knockdown at a low oxygen tension. By interacting with Parkin, p53 inhibited the translocation of Parkin to the mitochondria, disrupting the protective mitophagy process. These results suggest that TAT-ODD-p53 has a significant and preferential radiosensitizing effect on hypoxic breast cancer cells by inhibition of Parkin-mediated mitophagy.

At what age should screening mammography be recommended for Asian women?

Although regular screening mammography has been suggested to be associated with improvements in the relative survival of breast cancer in recent years, the appropriate age to start screening mammography remains controversial. In November 2009, the United States Preventive Service Task Force published updated guidelines for breast cancer, which no longer support routine screening mammography for women aged 40–49 years, but instead, defer the choice of screening in that age group to the patient and physician. The age to begin screening differs between guidelines, including those from the Task Force, the American Cancer Society and the World Health Organization. It remains unclear how this discrepancy impacts patient survival, especially among certain subpopulations. Although the biological characteristics of breast cancer and peak age of incidence differ among different ethnic populations, there have been few reports that evaluate the starting age for screening mammography based on ethnicity. Here, we discuss the benefits and harm of screening mammography in the fifth decade, and re-evaluate the starting age for screening mammography taking ethnicity into account, focusing on the Asian population. Breast cancer incidence peaked in the fifth decade in Asian women, which has been thought to be due to a combination of biological and environmental factors. Previous reports suggest that Asian women in their 40s may receive more benefit and less harm from screening mammography than the age-matched non-Asian US population. Therefore, starting screening mammography at age 40 may be beneficial for women of Asian ethnicity in well-resourced countries, such as Japanese women who reside in Japan.

Lentivirus-Mediated Short-Hairpin RNA Targeting Protein Phosphatase 4 Regulatory Subunit 1 Inhibits Growth in Breast Cancer.

PurposeProtein phosphatase 4 regulatory subunit 1 (PP4R1), as an interaction partner of the catalytic serine/threonine-protein phosphatase 4 catalytic subunit has been shown to involve in cellular processes and nuclear factor κB signaling. However, the functions of PP4R1 in human breast cancers remain unclear. This study is designed to explore the effect of PP4R1 knockdown on the biological characteristics of breast cancer cells.MethodsA lentivirus-mediated short hairpin RNA (shRNA) was designed to knockdown the expression of PP4R1 in ZR-75-30 breast cancer cells. The efficiency of lentivirus-mediated shRNA infection was determined using fluorescence microscopy to observe lentivirus-mediated green fluorescent protein expression and confirmed to be over 80%. PP4R1 expression in infected ZR-75-30 cells was detected by quantitative real-time polymerase chain reaction and western blot analysis. Cell proliferation and colony formation ability were measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and colony formation assay, respectively. Flow cytometry was used to measure cell cycle progression and cell apoptosis. In addition, apoptosis makers, including poly-ADP-ribose polymerase (PARP) and caspase-3, were investigated in PP4R1-silenced ZR-75-30 cells by western blot assay.ResultsWe successfully constructed lentivirus-mediated shRNA to target PP4R1 in ZR-75-30 cells. MTT assay and colony formation assay showed the loss of PP4R1 suppressed the proliferation of ZR-75-30 cells. Flow cytometry analysis indicated cell cycle arrest and increased cell apoptosis in PP4R1 knockdown cells. Further, the apoptosis response in cells depleted of PP4R1 was illustrated by downregulation of PARP and upregulation of caspase-3.ConclusionOur results suggest that PP4R1 could promote breast cancer cell proliferation and might play a vital role in breast cancer occurrence.