Human Epithelial Receptor Research Articles

Treatment Problems In Triple Negative Breast Cancer

Background: Breast cancer ranks second on the list of common diseases worldwide. It causes many deaths in the United States and Europe, second only to lung cancer. Triple-negative breast cancer (TNBC) does not express Estrogen Receptor (ER), Progesterone Receptor (PR), and Human Epithelial Receptor (HER2). It represents 24% of new cases of all breast cancer, and its incidence increases yearly. TNBC is a hormone-resistant breast cancer, so no current standard therapy exists. This article aims to explore regimen-resistant and troubleshooting treatment responses in TNBC cases. The method of writing this article is a literature review of studies using the keywords triple-negative breast cancer treatment and regimen, which are limited to only the most recent articles, 2012-2022, using search engines from PubMed, Science Direct, and Google Scholar. Results: There is no definitive therapy for the triple-negative breast cancer subtype, in which the TNBC type has no target receptor. Chemotherapy is the SOC of TNBC for early stage treatment. For late-stage and relapsed TNBC, however, chemotherapy is no longer the first choice. Currently there is no standard chemotherapy regimen that can be given to patients who experience relapse after chemotherapy because they will have a short response and lead to metastases. Some studies have shown that chemotherapy gives a better response, but the prognosis of TNBC remains poor. TNBC has different responses to therapy. TNBC showed a good response to combination chemotherapy along with pembrolizumab, capecitabine, olaparib, and radiotherapy, compared to chemotherapy by itself. Surgical therapy, such as Breast-Conserving Surgery (BCS), does not improve better prognosis in TNBC patients. Conclusions: Combining pembrolizumab, olaparib, capecitabine, and radiotherapy with chemotherapy increased survival rates compared to chemotherapy only.

Biospecific Monolayer Coating for Multivalent Capture of Circulating Tumor Cells with High Sensitivity

AbstractThe isolation and detection of rare circulating tumor cells (CTCs) from patient peripheral blood can help to monitor the metastatic spread of carcinoma and evaluate therapeutic outcomes. However, it is technically challenging to isolate CTCs due to extreme rarity in blood. Current techniques typically have to utilize complex instrumentation to capture CTCs, resulting in nonapplicability. Inspired from the mussel adhesion, a polyglycerol‐based block polymer is used to fabricate a biospecific and bioinert interface for isolating CTCs with high selectivity and efficiency. Benefitting from the antifouling polyglycerol, the resulting monolayer coating greatly suppresses the nonspecific cells adhesion. Compared with one anti‐epithelial cell adhesion molecule (anti‐EpCAM), the CTCs' capture efficiency was improved to 95% when multiple receptors, i.e. anti‐EpCAM/Human epithelial receptor 2 (Her2)/Epithelial Growth Factor receptor (EGFR) are employed, even for low EpCAM‐expressing CTCs. The CTCs detection limit on the presented surface is as low as 1 cell mL−1. Furthermore, CTCs are isolated from breast cancer patients' blood sample with a high selectivity. Also, the CTCs can be released and still keep proliferation capability for downstream analysis. This multifunctional block polymer surface coating is quite cost effective and highly applicable for CTCs' isolation in the clinic, which can provide a new prospect for designing the next‐generation of bio/nanointerfaces for biomedical studies.

Pituitary, Gonadal, Thyroid Hormones and Endocrine Disruptors in Pre and Postmenopausal Nigerian Women with ER-, PR- and HER-2-Positive and Negative Breast Cancers.

Breast cancer is broadly sub-divided into hormone responsive and non-hormone responsive subtypes. Estradiol has been associated with hormone responsive breast cancers. There is, however, a paucity of information on the role of sex hormones, gonadotropins, and thyroid hormone in non-hormone responsive breast cancer. This study aimed to determine differences in the serum levels of sex hormones, gonadotropins, thyroid hormones, and endocrine disruptors (lead, cadmium, and arsenic) in Nigerian women with hormone responsive and non-hormone responsive breast cancers. Seventy-nine non-pregnant women aged 28–80 years with histologically confirmed breast cancer were recruited, pre-therapy, into this cross-sectional study. They comprised 52 premenopausal women and 27 postmenopausal women recruited from the Surgical Oncology Clinic of the Department of Surgery, University College Hospital, Ibadan. Comparison of biochemical parameters were based on the positivity (+) and negativity (−) of estrogen receptor (ER), progesterone receptor (PR) and human epithelial receptor-2 (HER-2). Estradiol, progesterone, follicle stimulating hormone (FSH), luteinizing hormone (LH), free thyroxine (FT4), free triiodothyronine (FT3), and thyroid stimulating hormone (TSH) were determined using enzyme immunoassay (EIA). Serum lead, cadmium and arsenic were determined using atomic absorption spectrophotometry (AAS). Expression of ER, PR and HER2 were determined using immunohistochemistry. Data was analyzed using Mann-Whitney U-test and multiple regression, with p < 0.05 considered as being statistically significant. Estradiol and progesterone were significantly higher in breast cancer participants with ER− and PR− compared with those with ER+ and PR+ breast cancer (p < 0.05). Follicle stimulating hormone and LH levels were significantly higher in participants with ER+ and PR+ breast cancer compared with participants with ER− and PR− breast cancer (p < 0.05). Arsenic was inversely related with TSH in premenopausal participants with ER− and PR− (β = −0.305; β = −0.304, respectively). Sex hormones and gonadotropins appear to be involved in the pathogenesis of triple negative and luminal breast cancer, respectively.

First-in-human phase 0 study of 111In-CHX-A"-DTPA trastuzumab for HER2 tumor imaging.

Introduction:Tumors over-expressing the human epithelial receptor 2 (HER2) or exhibiting amplification or mutation of its proto-oncogene have a poorer prognosis. Using trastuzumab and/or other HER2 targeted therapies can increase overall survival in patients with HER2(+) tumors making it critical to accurately identify patients who may benefit. We report on a Phase 0 study of the imaging agent, 111In-CHX-A”-DTPA trastuzumab, in patients with known HER2 status to evaluate its safety and biodistribution and to obtain preliminary data regarding its ability to provide an accurate, whole-body, non-invasive means to determine HER2 status.Methods:111In-CHX-A”-DTPA trastuzumab was radiolabeled on-site and slowly infused into 11 patients who underwent single (n=5) or multiple (n=6) ɣ-camera (n=6) and/or SPECT (n=8) imaging sessions.Results:No safety issues were identified. Visual and semi-quantitative imaging data were concordant with tissue HER2 expression profiling in all but 1 patient. The biodistribution showed intense peak liver activity at the initial imaging timepoint (3.3h) and a single-phase clearance fit of the average time-activity curve (TAC) estimated t1/2=46.9h (R2=0.97; 95%CI 41.8 to 53h). This was followed by high gastrointestinal (GI) tract activity peaking by 52h. Linear regression predicted GI clearance by 201.2h (R2 =0.96; 95%CI 188.5 to 216.9h). Blood pool had lower activity with its maximum on the initial images. Non-linear regression fit projected a t1/2=34.2h (R2 =0.96; 95%CI 25.3 to 46.3h). Assuming linear whole-body clearance, linear regression projected complete elimination (x-intercept) at 256.5hr (R2=0.96; 95%CI 186.1 to 489.2h).Conclusion:111In-CHX-A”-DTPA trastuzumab can be safely imaged in humans. The biodistribution allowed for visual and semiquantitative analysis with results concordant with tissue expression profiling in 10 of 11 patients. Advances in Knowledge and Implications for Patient Care Using readily available components and on-site radiolabeling 111In-CHX-A”-DTPA trastuzumab SPECT imaging may provide an economical, non-invasive means to detect HER2 over-expression.

Comparison of Tumor Recurrence After Resection of Highly- and Poorly-Metastatic Triple-negative Breast Cancer in Orthotopic Nude-Mouse Models

Triple-negative breast cancer (TNBC), defined by the absence of receptors for estrogen, progesterone and human epithelial receptor 2, is a recalcitrant disease in need of effective therapy. We previously isolated highly-metastatic variants of the human TNBC cell line MDA-MB-231 using serial orthotopic implantation in nude mice. In the present report, we compared local and metastatic recurrence in lymph nodes in orthotopic nude-mouse models after bright-light surgery (BLS) of tumors from highly-metastatic variants or poorly-metastatic parental MDA-MB-231-RFP cells. Orthotopic tumors from parental MDA-MB-231 or highly-metastatic MDA-MB-231 were resected under bright light similar to an operating room. After resection of primary tumors, local recurrence from highly-metastatic MDA-MB-231 cells grew more rapidly than did parental MDA-MB-231 cells. Lymph-node metastasis from highly-metastatic MDA-MB-231 cells occurred after primary tumor resection much more extensively than after parental MDA-MB-231 tumors were resected. The results of the present report suggest that conventional surgery under bright light was unable to control highly-metastatic compared with poorly-metastatic MDA-MB-231 TNBC.

In Vivo Selection of Intermediately- and Highly-Malignant Variants of Triple-negative Breast Cancer in Orthotopic Nude Mouse Models.

Triple-negative breast cancer (TNBC), defined by the absence of receptors for estrogen, progesterone and human epithelial receptor 2 (HER2), is a recalcitrant disease in need of effective therapy. We previously isolated very-highly metastatic variants of the TNBC cell line MDA-MB-231 using serial orthotopic implantation of MDA-MB-231 human breast cancer cells in nude mice. MDA-MB-231 cells expressing red fluorescent protein (MDA-MB-231-RFP) (1×107 cells/site) were initially injected subcutaneously in the flank of nude mice. After the subcutaneous tumors grew, they were harvested and cut into small pieces for orthotopic implantation into the right lower mammary gland. After the orthotopic tumors grew, they were resected and cut into small pieces and orthotopically re-implanted into the mammary gland of nude mice. The tumors grew and metastasized to lymph nodes. The lymph node metastases were harvested and cut into small pieces and orthotopically re-implanted into the mammary gland of nude mice. After the orthotopic tumors grew, the tumor was removed leaving residual cancer cells, which grew and metastasized to lymph nodes. The lymph node metastases were harvested, cut into pieces and orthotopically re-implanted into the mammary gland of nude mice for three or seven cycles in order to isolate intermediately, or highly-metastatic variants, respectively. The degree of malignancy of isolated variants of MDA-MB-231 depends on the extent of orthotopic transplantation. Serial transplantation resulted in MDA-MB-231-RFP which significantly produced larger tumors compared with the parental MDA-MB-231-RFP. Serial orthotopic implantation for three cycles resulted in intermediately-metastatic variants of MDA-MB-231-RFP. MDA-MB-231-RFP serially orthotopically transplanted seven times significantly metastasized more to lymph nodes compared with parental MDA-MB-231-RFP cells and the intermediately-metastatic variant. The highly-metastatic variant MDA-MB-231-RFP cells significantly metastasized to the lung to a greater extent compared with parental MDA-MB-231-RFP and intermediate variants of MDA-MB-231-RFP. These results suggest that the number of serial orthotopic transplantations of MDA-MB-231-RFP correlates positively with tumor aggressiveness, and the intermediately- and highly-metastatic variants can serve as models of metastatic progression of TNBC.

Metaplastic carcinoma of the breast: A case series and review of the literature

Abstract Purpose Metaplastic breast carcinoma (MBC) is a rare aggressive type of breast cancer, which accounts for less than 1% of breast tumors. Since its recognition as a distinct pathological entity in 2000, number of MBC patients has been increasing over years. We aimed to report a series of 7 cases of MBC treated in our clinics. Materials and methods Between 2006 and 2015, 7 cases with diagnosis of MBC were retrospectively reviewed. Patients' characteristics, clinicopathological features and types of surgery were evaluated. Results All patients were female with a median age of 51(40–65) years. Median tumor size was 40 mm (35–85 mm). Two patients had breast-conserving surgery and 4 patients had mastectomy. One patient received chemotherapy due to extensive metastatic disease at the time of presentation. Only one patient had one positive sentinel lymph node with no other involvement in the non-sentinel nodes. Two patients had spindle cell carcinoma, 2 patients had pure epithelial type, and 3 patients had mixed epithelial and mesenchymal type MBC. Most common component of MBC was squamous cell metaplasia that was found in 4 out of 7 patients. Six patients had triple negative tumors except the patient with disseminated disease. This patient had estrogen receptor positive, progesterone receptor negative tumor with human epithelial receptor-2 (HER2) over-expression. Median Ki67 score measured in 5 patients was 57% (40–95%). Conclusion Our small series is consistent with the literature. MBC rarely metastasize to axillary lymph nodes despite large size and are usually triple negative with high Ki-67 scores indicating aggressiveness and lack of response to hormonal therapy. Larger series of patients are needed to find and test new biomarkers to develop potential targeted therapy for subgroups of the disease.

Sex Hormones, Oestrogen Receptor, Progesterone Receptor and Human Epithelial Receptor 2 Expressions in Pre and Postmenopausal Sub-Saharan African Women with Breast Cancer

Aim: This study was carried out to determine the serum levels of sex hormones and gonadotropins as well as the expression of oestrogen receptor (ER), progesterone receptor (PR) and human epithelial receptor 2 (HER 2) in pre and postmenopausal women with breast cancer. Study Design: Case-control study. Place and Duration of Study: Surgical Oncology Clinic, University College Hospital, Ibadan, Nigeria between April 2011 and July 2014. Methodology: 169 non-pregnant women aged 48.3±1.3 years were recruited for this study. They comprised of 85 histologically confirmed breast cancer pre-therapy (cases) matched with 84 Original Research Article Ajayi et al.; JCTI, 3(4): 1-11, 2016; Article no.JCTI.25259 2 apparently healthy women without breast cancer (controls) according to age and menstrual phase. Both cases and controls were subdivided into pre and postmenopausal groups (54 premenopausal cases; 31 postmenopausal cases; 53 premenopausal controls; 31 postmenopausal controls respectively). Anthropometry and reproductive history were obtained by standard methods. Blood (10ml) was obtained from participants and centrifuged to obtain serum. Oestradiol, progesterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) were determined using enzyme immunoassay (EIA). Expression of ER, PR and HER 2 were determined by immunohistochemistry. Data analysed by Chi-square, Student’s t-test and multiple regression were considered statistically significant at p<0.05. Results: All premenopausal cases (100%) had ER and PR receptor negative expressions out of which 46(88.5%) had HER 2 receptor negative expression. Oestradiol and progesterone were significantly higher in postmenopausal cases compared with controls (p<0.05) while FSH and LH were significantly higher in premenopausal cases than controls (p<0.05). Conclusion: The pathophysiology of breast cancer may be based on menstrual phase. Elevated gonadotropins and sex hormones may be important in premenopausal and postmenopausal women with breast cancer. Triple negative breast cancer observed in 88.5% of premenopausal women with breast cancer is critical in the management of the disease especially in younger women.

Evaluation of the Expression of the Human Epithelial Receptor 2 (HER2) in Gastric Carcinoma.

Objective. To evaluate the HER2 expression on gastric adenocarcinoma from a Brazilian population and also to analyze the relations between the receptor and clinical characteristics, as well as the survival status. Materials and Methods. A retrospective analysis was conducted from January of 2008 to July of 2012, considering only gastrectomies with curative intent. Tumors were tested for HER2 status using immunohistochemistry. The relation between HER2 status and clinical aspects, surgical findings, and survival were also analyzed. Results. 222 patients with gastric carcinoma were submitted to surgery during that period, but only 121 (54,5%) were with curative intention. The immunohistochemistry revealed that 4 patients (3,3%) were HER2-positive, 6 patients (4,9%) HER2-undetermined, and 111 patients (91,7%) HER2-negative. There was no statistical concordance between HER2 status and survival or the clinical aspects. Conclusion. The HER2 overexpression rate was very low in this Brazilian population sample and cannot be considered as a prognostic factor.

English

Background: Breast cancer markers are becoming increasingly important in breast cancer research due to their impact on prognosis, treatment and survival. The present retrospective study was carried out to quantify the proportion of estrogen (ER), progesterone (PR), and human epithelial receptor 2 (HER2) expressions and their association with tumour grade, age, and tumour size in breast cancer patients in Nigeria. Materials and methods: The paraffin embedded tissue sections were analysed for breast cancer markers using monoclonal antibody SP1 for ER and SP2 for PR and polyclonal antibody ErbB2 for HER2. Results: A total of 286 breast cancer paraffin wax tissue sections were analysed for ER, PR and HER2 expression. Of all the tissue samples examined, 20 (7%) were ERpositive, 6 (2.1%) were PR-positive, 11 (3.8%) were HER2-positive whereas 248 (87%) were triple-negative breast carcinoma. ER- and PR-positivity was associated with early grade I and II tumours (P  0.010-0.009) and tumour sizes of  50mm (p  0.001). HER2positivity was positively (P  0.009) associated with grade II tumours and negatively (P  0.0001) associated with grade III tumours. Triple-negative breast cancer was associated with grade III tumours (P  0.0001) and larger tumour sizes of  50mm (P  0.0001). Conclusion: A small proportion of Nigerian women with breast cancer are ER/PR-positive which are associated with less aggressive, better prognosis and benefit from endocrine therapy. An even smaller proportion of patients with aggressive tumors were HER2posivite but responsive to Herceptin treatment. Unfortunately, a very high proportion of cases were triple-negative which is associated with very aggressive tumours and no targeted treatment, which may explain the high mortality rates from breast cancer in Nigeria.

Targeted nanoparticles for simultaneous delivery of chemotherapeutic and hyperthermia agents – An in vitro study

The purpose of this study was to prepare targeted Poly lactide-co-glycolide (PLGA) nanoparticles with simultaneous entrapment of indocyanine green (ICG) and doxorubicin (DOX) by surface decorating them with tumor specific monoclonal antibodies in order to achieve simultaneous therapy and imaging. ICG was chosen as an imaging and hyperthermia agent and DOX was used as a chemotherapeutic agent. ICG and DOX were incorporated into PLGA nanoparticles using the oil-in-water emulsion solvent evaporation technique. These nanoparticles were further surface decorated with antibodies against Human Epithelial Receptor-2 (HER-2) using carbodiimide chemistry. The uptake of antibody conjugated ICG-DOX-PLGA nanoparticles (AIDNP) was enhanced in SKOV-3 (HER-2 overexpressing cell lines) compared to their non-conjugated counterparts (ICG–DOX–PLGA nanoparticles (IDNP)). The uptake of antibody conjugated ICG–DOX–PLGA nanoparticles, however, was similar in MES-SA and MES-SA/Dx5 cancer cells (HER-2 negative cell lines), which were used as negative controls. The cytotoxicity results after laser treatment (808nm, 6.7W/cm2) showed an enhanced toxicity in treatment of SKOV-3. The negative controls exhibited comparable cytotoxicity with or without exposure to the laser. Thus, this study showed that these antibody conjugated ICG–DOX–PLGA nanoparticles have potential for combinatorial chemotherapy and hyperthermia.

Serum soluble ST2 is associated with ER-positive breast cancer

BackgroundST2, a member of the interleukin (IL)-1receptor family, regulates Th1/Th2 immune responses in autoimmune and inflammatory conditions. However, the role of ST2 signaling in tumor growth and metastasis of breast cancers has not been investigated. This study investigated the possible role of soluble ST2 (sST2) in breast cancer.MethodsThe serum levels of IL-33, sST2, and vascular endothelial growth factor (VEGF) in 150 breast cancer patients and 90 healthy women were measured by enzyme-linked immunosorbent assay. Estrogen receptor(ER), progesterone receptor, human epithelial receptor (HER)-2, and cell cycle regulated protein Ki-67 were measured. Clinical stage, tumor size, lymph node metastasis, and histological type were also recorded.ResultsThe serum levels of sST2, IL-33, and VEGF were significantly higher in breast cancer patients than in the control group (P < 0.05, each). Serum sST2 levels in ER-positive breast cancer patients were significantly associated with age, histological type, clinical stage, tumor size, and Ki-67 status (P < 0.05, each). Moreover, the serum levels of IL-33 and sST2 in breast cancers significantly correlated with VEGF levels (IL-33: r = 0.375, P < 0.0001; sST2: r = 0.164, P = 0.045). Serum levels of sST2, IL-33, and VEGF decreased after modified radical mastectomy in ER-positive breast cancers. Serum levels of IL-33, sST2, and VEGF and clinicopathological factors were not significantly correlated with disease-free survival and overall survival of ER-positive breast cancer women during follow-up.ConclusionSerum sST2 levels in ER-positive breast cancer patients are significantly associated with factors that indicate poor prognosis.

PP061: Genetic expressions of ER/PR and HER2/neu among salivary gland tumour patients at UCH Ibadan

Acinar and ductal structures are found in normal breast and salivary gland tissue, also similar histopathological findings were revealed by some neoplasm from these tissues therefore the role of ER/PR and HER2/neu as molecular targets in breast cancer were projected to salivary gland tumours (SGT’s). The purpose of this study was to determine the levels of expression of these genes which may be indicators for targeted therapy in SGT’s. The study utilised sections of hematoxylin-eosin (H&E) and IHC sections of antibody panels to estrogen (ERα), progesterone (PR) and Human Epithelial Receptor (HER2) as specified by the manufacturer (Dako Cytomation, USA). 40 salivary gland tumour specimen from 19 males (47.5%) and 21 females (52.5%) were utilised (age range was 6–75 years; mean 45.4 ± 16.6 years) there were 15 benign and 25 malignant cases. There was a definite increased positive expression of oestrogen receptor with increasing clinical stage ( x 2 = 5.6; p = 0.00) and higher histological grades irrespective of sex and histological type ( X 2 = 4.2; p = 0.04 Fisher’s exact) while the positive expression of PR was generally low irrespective of sex, clinical stage, histological type and grade of malignant SGT’s. There was lack of positive expression of HER2/neu among all benign SGT’s while only one high grade acinic cell carcinoma showed minimal positive expression among the malignant SGT’s. ERα receptor may be a suitable molecular target for therapy of high grade malignant SGT that show positive expression, the role of PR receptor targeted therapy is doubtful in malignant SGT’s. None of the SGT’s showed convincing positive HER2/neu expression.

Analysis of indoleamine 2-3 dioxygenase (IDO1) expression in breast cancer tissue by immunohistochemistry

The immunosuppressive enzyme, indoleamine 2,3 dioxygenase (IDO), is overexpressed in many different tumor types including breast cancer. IDO inhibitors synergize with chemotherapy in breast cancer murine models. Characterizing IDO expression in breast cancer could define which patients receive IDO inhibitors. This study analyzed IDO protein expression in 203 breast cancer cases. The relationship between IDO, overall survival (OS), disease-specific survival (DSS), clinicopathologic, molecular, and immune tumor infiltrate factors was evaluated. Expression of IDO, estrogen receptor (ER), progesterone receptor (PR), human epithelial receptor 2, cytokeratin 5/6, epithelial growth factor receptor, phosphorylated AKT, neoangiogenesis, nitrogen oxide synthetase 2 (NOS2), cyclooxygenase 2 (COX2), FoxP3, CD8, and CD11b on archival breast cancer tissue sections was evaluated by immunohistochemistry. Associations between IDO and these markers were explored by a univariate and multivariate analysis. Survival was analyzed using Kaplan-Meier (OS) and Wilcoxon two-sample (DSS) tests. IDO expression was higher in ER+ tumors compared to ER- tumors. IDO was lower in those with higher neoangiogenesis. OS was better in ER+ patients with high IDO expression. DSS was better in node-positive patients with high IDO expression. IDO activity positively correlates with NOS2. COX2 as positively correlated with IDO on univariate but not multivariate analysis. There was a trend toward greater numbers of CD11b+ cells in IDO-low tumors. IDO protein expression is lower in ER- breast tumors with greater neoangiogenesis. Future clinical trials evaluating the synergy between IDO inhibitors and chemotherapy should take this finding into account and stratify for ER status in the trial design.

Ciblage des récepteurs ErbB2 par immuno-histochimie et FISH pour cas équivoque, chez 160 patientes atteintes d’un cancer du sein de l’ouest Algérien

Summary The determination of Human Epithelial receptor 2 (HER2) status by immunohistochemistry (IHC) is very important for diagnosis since the appearance of Trastuzamab in adjuvant and neoadjuvant breast cancer. The objective set for this study was to evaluate the overexpression of HER2 in 160 patients with invasive breast cancer, because of the involvement of erbB family receptors (epidermal growth factor receptor) in breast oncogenesis. The assessment of HER2 status is semi-quantitative, and is following a defined scale: score 1 + (negative), score 2 + (verification of gene amplification by FISH or CISH more objective and quantitative IHC), score 3 + (positive). Our strategy is purely and prognosis is to redo the IHC scores of 2, once you realize the score confirmed a FISH (fluorescence in situ hybridization), and 50 patients have undergone evaluation of HER2 gene amplification/neu. The indication for treatment Herceptin® scores for IHC and FISH amplified 3. The majority of cases are invasive ductal carcinomas: 84.37% of cases. Our results were as follows: 22.25% are HER2 +1, 31.25% HER2 +2, 46.25% HER2 +3. A monoclonal antibody against the HER2 receptor, trastuzumab (Herceptin®) is used as a treatment for women with HER2+. Our case series, although limited to permits to handle patients scoring 2, which in itself is a first and a big step for our laboratory.

Inflammatory breast cancer in Morocco: Experience of Hassan II University Hospital.

e11516 Background: Inflammatory breast cancer (IBC) is the most virulent type of breast cancer. It represents 1 to 6% of all the breast cancer in Western countries. It is speculated that the incidence of IBC is greater in emerging countries especially in North Africa. The management of this disease requires a multidisciplinary. Methods: We recorded the cases of 80 patients with IBC admitted in the Medical Oncology Unit between January 2007 and August 2011. We included patients with IBC classified as T4d using criteria based on the tumor-node-metastasis (TNM) classification . The aims of this study is to evaluate the epidemiological, clinical, histopathological and therapeutic aspects of this disease. Results: The median age of our patients was 44.5 years ranged from 24 to 88 years. The incidence of IBC in our study was 7.8%. The lymph node involvement was noted in 60% distributed as following: N0 in 40%, N1 in 30%, N2 in 19%, N3 in 11%. For histology, ductal carcinoma represents 96% of all cases. Human epithelial receptor 2 (HER 2) was positive in 32% of the cases. Hormonal receptors were negative in 22% of the cases. The grade of the tumor according to the Scarff Bloom Richardson classification was as following: grade I ( 2.5%), grade II (52%), grade III (45.5%). All patients received neoadjuvant chemotherapy. 45% received chemotherapy with anthracyclines, 35% were treated with docetaxel and anthracycline and 10% with the association chemotherapy Trastuzumab. According to RECIST classification, a partial or total clinical response was noted in 80% of cases, 10% of patients had stability, and 10% clinical progression. According to Sattalof classification, a histological response greater than 50% in the tumor (TB) was noted in 45%. A complete pathological response (TANA or TANB) was obtained in 15% of cases. After a median follow up of 2 years 35% of the patients had a metastatic or locoregional reccurence, 45% of the cases remain in complete remission. Conclusions: The result of our study is concordant with the litterature. The incidence of IBC was greater than the incidence in western countries. The IBC was also associated with high grade and younger age. Despite a good clinical and pathological response to chemotherapy, outcomes were poor.

Pattern of distant recurrence according to the molecular subtypes in Korean women with breast cancer

BackgroundDistant recurrence is one of the most important risk factors in overall survival, and distant recurrence is related to a complex biologic interaction of seed and soil factors. The aim of the study was to investigate the association between the molecular subtypes and patterns of distant recurrence in patients with breast cancer.MethodsIn an investigation of 313 women with breast cancer who underwent surgery from 1994 and 2000, the expressions of estrogen and progestrone receptor (ER/PR), and human epithelial receptor-2 (HER2) were evaluated. The subtypes were defined as luminal-A, luminal-HER2, HER2-enriched, and triple negative breast cancer (TNBC) according to ER, PR, and HER2 status.ResultsBone was the most common site of distant recurrence. The incidence of first distant recurrence site was significantly different among the subtypes. Brain metastasis was more frequent in the luminal-HER2 and TNBC subtypes. In subgroup analysis, overall survival in patients with distant recurrence after 24 months after surgery was significantly different among the subtypes.ConclusionsOrgan-specific metastasis may depend on the molecular subtype of breast cancer. Tailored strategies against distant metastasis concerning the molecular subtypes in breast cancer may be considered.

Vascular endothelial growth factor receptors and the therapeutic targeting of angiogenesis in cancer: where do we go from here?

Abstract Vascular Endothelial Growth Factor receptors (VEGFRs), the interactions with their ligands and the subsequent signalling pathways are known to play a vital role in tumour angiogenesis. Initial clinical trials of VEGFR inhibitors were disappointing but over the past decade some therapies have been successfully brought to market. At present, VEGFR inhibitors appear to be most promising as adjuvants to conventional chemotherapy. However, several interacting signalling molecules and downstream pathways have recently been shown to interact with VEGFR signalling and provide promising novel targets, such as the platelet-derived growth factor (PDGF), epithelial growth factor (EGF), human epithelial receptor-2, (HER-2) Tie-2 and oestrogen receptors. Elucidation of this web of signalling pathways may identify new therapeutic strategies which may be used in combination with VEGFR inhibitors to augment the efficacy of anti-angiogenic cancer treatments. This review assesses the role of modulating VEGFR activity in cancer and systematically examines current evidence and trials in this area.

Involvement of Depressive Catecholamines as Thrombosis Risk/Inflammatory Markers in Non-Smoker, Non-Obese Congestive Heart Failure, Linked to Increased Epidermal Growth Factor-Receptor (EGF-R) Production

The EGF-R, also known as HER-1 or erbB-1 (EGF-R/HER-1/erbB-1), is a member of the human epithelial receptor tyrosine kinase family. sEGF-R is considered to play a role in cardiac (patho)physiology. We aimed to investigate whether soluble EGF-R is increased in congestive heart failure (CHF) patients and if related to disease severity. Soluble EGF-R, vitamin D, parathyroid hormone (PTH) was studied, and being evaluated in relation to Ca(2+), lipids, hsCRP, fibrinogen, serotonin, norepinepherine (NE). The study compared non-smoker, non-obese male CHF patients (n=50) with age and gender-matched essential hypertension (HTN) patients (n=20). Moreover, comparison with healthy control volunteers (n=20) were employed. EGF-R/HER-1/erbB-1 was higher (P=0.013) in 50 CHF male patients mean 12± 0.7fmol/ml, than in 20 HTN, 9.25±0.6fmol/ml or in 20 controls, 6.25±1fmol/ml. Serum EGF-R levels correlated positively with hsCRP and NE, and were highest among CVD patients (n=70) as well as negatively with vitamin D and HDL-C. EGF-R/HER-1/erbB-1 levels are increased in HTN and more in CHF patients. This study confirms a strong association between catecholamines as well as EGF-R/HER-1/erbB-1 levels with PTH and low vitamin D levels, being related to hyperlipidemia and inflammation (hsCRP and fibrinogen) in CVD. Moreover, contributing to the complex process of the inflammatory component of atherosclerosis in hypertensive patients that leads eventually to CHF.

Molecular subtypes of breast cancer and amplification of topoisomerase IIα: predictive role in dose intensive adjuvant chemotherapy

Benefit from chemotherapy treatment in breast cancer patients is determined by the molecular make-up of the tumour. In a retrospective analysis, we determined the molecular subtypes of breast cancer originally defined by expression microarrays by immunohistochemistry in tumours of patients who took part in a randomised study of adjuvant high-dose chemotherapy in breast cancer. In addition, the topoisomerase IIα (TOP2A) amplification status was determined by fluorescence in situ hybridisation and chromogenic in situ hybridisation. 411 of the 753 tumours (55%) were classified as luminal-like, 137 (18%) as basal-like and 205 (27%) as human epithelial receptor type 2 (HER2) amplified. The basal-like tumours were defined as having no expression of ER and HER2; 98 of them did express epidermal growth factor receptor and/or cytokeratin 5/6. The luminal-like tumours had a significantly better recurrence free and overall survival than the other two groups. From the 194 HER2-positive tumours, 47 (24%) were shown to harbour an amplification of TOP2A. Patients with an HER2-amplified tumour randomised to the high-dose therapy arm did worse than those in the conventional treatment arm, possibly caused by the lower cumulative anthracycline dose in the high-dose arm. The tumours with a TOP2A amplification contributed hardly to this difference, suggesting that TOP2A amplification is not the cause of the steep dose–response curve for anthracyclines in breast cancer. Possibly, the difference of the cumulative dose of only 25% between the treatment arms was insufficient to yield a survival difference.