Predictive Factors In Breast Cancer Research Articles

Impact of hormone receptor status and tumor subtypes on clinical behavior and outcomes of breast cancer in young BRCA carriers.

504 Background: Hormone receptor expression is a known positive prognostic and predictive factor in breast cancer (BC). Among young patients harboring germline BRCA1or BRCA2 (BRCA) pathogenic variants (PVs), most of the tumors arising in BRCA2carriers express hormone receptors, while most BC cases in BRCA1 carriers do not; however, limited evidence exists on the impact of hormone receptor status on clinical behavior and outcomes in young patients harboring BRCA PVs. Methods: This is an international, multicenter, hospital-based, retrospective cohort study including young patients (≤40 years) diagnosed with invasive BC between January 2000 and December 2020, harboring germline PVs in BRCA genes. Our analysis investigates the impact of hormone receptor status on clinical behavior and outcomes of BC. The type and pattern of recurrence and survival outcomes (disease-free survival [DFS], BC specific survival [BCSS] and overall survival [OS]) were first investigated according to hormone receptors expression (positive vs. negative), and then according to BC subtype (luminal A-like vs. luminal B-like vs. triple-negative vs. HER2-positive BC). Results: From 78 centers worldwide, 4,709 BRCA carriers were included in this analysis, of whom 2,143 (45.5%) had hormone receptor-positive and 2,566 (54.5%) hormone receptor-negative BC. Patients with hormone receptor-positive BC were more likely to harbor BRCA2 PVs while less frequently had grade 3 tumors and nodal involvement. Median follow-up was 7.88 (IQR 4.47-12.61) years. The rate of distant recurrences was higher in patients with hormone receptor-positive BC (13.1% vs. 9.6%, p<.001), while the rate of second primary BC was lower (9.1% vs. 14.7%, p<.001) when compared to patients with hormone receptor-negative disease. The 8-years DFS was 65.8% in patients with hormone receptor-positive and 63.4% in those with hormone receptor-negative BC. No differences in terms of OS nor BCSS were observed. The hazard ratio of hormone receptor-positive vs. negative disease changed over time for DFS, BCSS, and OS (p<.05 for interactions of hormone receptor status and survival time). Among the 4,363 patients eligible for subtypes analysis, 612 had luminal A-like, 1,038 luminal B-like, 2,373 triple-negative and 340 HER2-positive BC. Patients with Luminal A-like BC had the worst long-term prognosis in terms of DFS compared to all the other subgroups (8-years DFS: 60.8% in luminal A-like vs. 63.5% in triple-negative vs. 65.5% in HER2-positive and 69.7% in luminal B-like subtype). Conclusions: In young BRCAPVs carriers with early BC, hormone receptor status did not appear to be a positive prognostic factor. The differences in pattern of recurrence and second primary BC among hormone receptor-positive vs. negative disease warrants consideration in counseling patients on treatment, follow-up strategies and indication for risk-reducing surgery.

Steroid profile in patients with breast cancer and in mice treated with mifepristone.

Progesterone receptors (PRs) are biomarkers used as prognostic and predictive factors in breast cancer, but they are still not used as therapeutic targets. We have proposed that the ratio between PR isoforms A and B (PRA and PRB) predicts antiprogestin responsiveness. The MIPRA trial confirmed the benefit of 200 mg mifepristone, administered to patients with tumors with a high PRA/PRB ratio, but dose-ranging has not been conducted. The aim of this study was to establish the plasma mifepristone levels of patients from the MIPRA trial, along with the resultant steroid profiles, and compare these with those observed in mifepristone-treated mice using therapeutic schemes able to induce the regression of experimental mammary carcinomas with high PRA/PRB ratios: 6 mg pellets implanted subcutaneously, or daily doses of 12 mg/kg body weight. The plasma levels of mifepristone and other 19 plasma steroids were measured by liquid chromatography-tandem mass spectometry. In mifepristone-treated mice, plasma levels were lower than those registered in mifepristone-treated patients (i.e. day 7 after treatment initiation, pellet-treated mice: 8.4 ± 3.9 ng/mL; mifepristone-treated patients: 300.3 ± 31.7 ng/mL (mean ± s.d.; P < 0.001)). The increase in corticoid related steroids observed in patients was not observed in mifepristone-treated mice. The increase in progesterone levels was the most significant side effect detected in mifepristone-treated mice after 14 or 21 days of treatment, probably due to an ovarian compensatory effect not observed in postmenopausal patients. We conclude that in future clinical trials using mifepristone, the possibility of lowering the standard daily dose of 200 mg should be considered.

Prognostic and predictive value of a novel 100-point scale in patients with T1–2N0M0 breast cancer

Aim. To increase the efficacy of systemic breast cancer therapy and reduce inappropriate prescriptions using individual immunohistochemical tumor characteristics, as well as to develop prognostic scales to ensure a tailored approach to adjuvant systemic treatment in breast cancer patients. Materials and methods. We conducted a comprehensive study that included collection of literature data on clinical, pathomorphological, prognostic, and predictive factors of breast cancer, as well as a retrospective cohort study using the data from the cancer registry. We also performed histological and immunohistochemical examination of tumor tissue samples from breast cancer patients (for the retrospective cohort study) and statistical data analysis. A total of 1,216 patients with T1–2N0M0 breast cancer were included in this study. Histological and immunohistochemical examinations of tissue samples (paraffin blocks) were conducted in the laboratory of N. N. Petrov National Medical Research Center of Oncology. We stained slides for both routinely used markers (including estrogen receptors, progesterone receptors, HER2, and Ki-67) and other markers (CK14, FOXA1, FOXP3, PD-L1, P53, SMA, androgen receptors, E-cadherin, CD4, CD8, CK5 / 6, EGFR).We analyzed risk factors for lethal outcomes in patients from this group to develop prognostic scales and compared their results. Results. We evaluated the most clinically and statistically significant factors affecting mortality. Using logistic regression, we chose 10 factors that had the greatest impact on the outcomes and then produced several scales, includinga 10-point regression scale (based on 10 most significant factors identified). Survival analysis in high-risk and low-risk patients using the regression scale demonstrated significant differences between these groups (р &lt;0.00001). The assessment of adjuvant chemotherapy efficacy in the combined group of intermediate- and high-risk patients (as estimated by the regression model) showed that intermediate- and high-risk patients receiving adjuvant chemotherapy had significant differences in their survival (р = 0.0057). The regression scale for 10-year prognosis demonstrated sufficient sensitivity (58.05 %), specificity (69.47 %) and ef fectiveness (63.76 %). Conclusion. Our regression prognostic scale includes markers with a high prognostic value. The multifactorial approach used in the developed regression scale for breast cancer 10-year prognosis increases its accuracy and reliability.

Relationship between Molecular Subtype, Degree of Differentiation, and Lymph Node Metastasis with Survival of Breast Cancer Patients at Dr. M. Djamil General Hospital, Padang, Indonesia

Background: Breast cancer has the highest incidence of all cancers in women worldwide. A molecular subtype of breast cancer, degree of differentiation, and lymph node metastasis are prognostic and predictive factors of breast cancer. This study aims to explore the relationship between molecular subtype, degree of differentiation, and lymph node metastasis with overall survival and disease-free survival of breast cancer patients at Dr. M. Djamil General Hospital Padang.&#x0D; Methods: This study was an analytic observational study with a retrospective cohort approach using secondary data from 68 subjects. The test variables in this study were the molecular subtype of breast cancer, the degree of differentiation, and lymph node metastasis which were obtained from secondary data and medical records. Another test variable is patient survival, namely overall survival (OS) and disease-free survival (DFS). Data analysis with the help of SPSS software in univariate, bivariate, and multivariate.&#x0D; Results: Patients with lymph node metastases were 7.94 times more likely to experience an event (death) (HR=7.94 95% CI: 0.91–78.2). Patients with lymph node metastases were 10.2 times more likely to experience an event (recurrence) (HR=10.2 95% CI: 1.03–101.1).&#x0D; Conclusion: Lymph node metastases are the factors most related to survival (overall survival and disease-free survival) of breast cancer patients at Dr. M. Djamil General Hospital, Padang, Indonesia.

Absolute Lymphocyte Count as an Independent Prognostic Factor in Metastatic Breast Cancer: A Retrospective Study

Introduction: Recently, absolute lymphocyte count (ALC) and neutrophil-to-lymphocyte ratio (NLR) have been reported to be prognostic and/or predictive factors in breast cancer. However, most of the investigations on the relationship between systemic inflammatory markers and prognosis have been conducted perioperatively, with few studies reporting on patients with metastatic or recurrent breast cancer (MBC). Here, we investigated the role of ALC and NLR as prognostic factors of MBC. Methods: This was a retrospective observational study of patients with MBC treated at the University of Tsukuba Hospital between 2013 and 2020. ALC and NLR clinical data were obtained from the patients’ charts. Based on the previous reports, the cutoff value of ALC was set at 1,500/µL and that of NLR, at 3. We investigated the prognostic significance of ALC and NLR. Results: About 80% of the 243 included patients were hormone receptor-positive, 20% were HER2-positive, and 10% were triple negative. The patients were grouped as follows: 114 (46.9%) and 129 (53.1%) in the high and low ALC groups and 145 (59.7%) and 98 (40.3%) in the high and low NLR groups, respectively. The group with high ALC at diagnosis of MBC showed significantly better prognosis (p = 0.002), and the median overall survival (OS) was 70.9 months, as compared with 40.2 months for the low ALC group. On multivariate analysis, visceral metastasis, subtype, and ALC were independent variables for OS; the NLR status was not correlated with OS. Conclusions: Analysis of real-world data suggests that ALC at diagnosis of MBC is an independent prognostic factor.

Significance of Bcl-2 expression in breast cancer

Introduction and Aim: The most prevalent and lethal form of cancer in women, breast carcinoma is thought to account for 2,088, 849 (11.6%) of all new cases each year. Protooncogene Bcl-2 is primarily present in the perinuclear membrane. Examining the significance of Bcl-2 expression as a predictive factor in breast cancer is the goal of the current investigation. Materials and Methods: From December 2019 to January 2021, a tertiary care hospital in Chennai conducted this investigation on 42 cases of mastectomy specimens. Using tools from Path Insitu, Bcl-2 marker immunohistochemistry was carried out. Scores were taken after observing Bcl-2 expression in the cytoplasm of tumor cells. Results: Total 42 cases were studied, and the age of patient ranged from 33-80 years. Out of 42 cases of IDC-NST (Invasive ductal carcinoma- No special type) 19 cases (45%) showed positive expression and 23 cases (54%) showed lack of staining for Bcl-2. Tumor size and grade of IDC-NST has significant relationship with Bcl-2 expression with p value of 0.05. No correlation has been found between lymph nodes harboring malignant cells and Bcl2 expression with p value &gt;0.05. Conclusion: The staging and prognosis of breast cancer depend heavily on the size, grading based on histopathology, and lymph node harboring tumor cells. Hormonal receptor tests are frequently used in the process of treating breast cancer. The goal of the current investigation was to assess Bcl2's value as an additional marker for prognosis. Significant Bcl-2 expression was seen in tumors of modest histologic grade and size.

A Five-Year Review of the Outcomes of Breast Imaging Reporting and Data System 4 Lesions in Hospital Universiti Sains Malaysia.

Purpose: The Breast Imaging Reporting and Data System (BI-RADS) lexicon used in reporting breast imaging has several categories with specific positive predictive values for breast cancer. Among those, BI-RADS 4 is associated with a wider range of risk for breast cancer, which makes the decision for biopsy difficult. The study aim was to determine the malignancy rate and clinical outcomes of BI-RADS 4 lesions in Hospital Universiti Sains Malaysia (HUSM) for a period of five years.Methods: This was a retrospective study of patients diagnosed by mammographic or ultrasonographic findings with BI-RADS 4 breast lesions in HUSM, Kelantan from July 2015 to June 2020. Data were collected from the medical records and an electronic database. Patients with BI-RADS 4 lesions who underwent biopsy and had a known tissue diagnosis were included in this study. The data was used to calculate the malignancy rate and associated positive predictive factors for breast cancer associated with BI-RADS 4 lesions.Results: From the mammography and ultrasonography performed at HUSM from July 2015 to June 2020, a total of 256 lesions were categorized as BI-RADS 4. However, only 198 BI-RADS 4 lesions underwent biopsy and were included in the study. Of these 198 lesions, 26.8% were malignant on histopathological examination of the biopsy samples. Simple logistic regression analysis showed that age, diabetes mellitus, hypertension, number of parity, and certain mammogram findings were significantly associated with breast cancer. Invasive breast cancer was the most common type. Fibrocystic disease was the most common benign pathology, followed by fibroadenoma.Conclusion: The malignancy rate of BI-RADS 4 lesions in HUSM was similar to previously reported rates. A thorough evaluation of positive predictive factors and careful selection of patients for biopsy in BI-RADS 4 lesions will minimize unwanted biopsies and associated patient anxiety, in addition to reducing the health care burden.

Receptorski status estrogena i progesterona karcinoma dojke operisanih žena u odnosu na godine starosti

Due to its frequency, morbidity and mortality, breast cancer represents the most significant malignancy in women. Oestrogen and progesterone receptor status is used as an important prognostic and predictive factor in breast cancer. The purpose of this research was to determine estrogen and progesterone receptor status of primary breast cancer relative to patient age. High receptor level indicates an active response to endocrine therapy. Studies have shown that about 70% of breast cancers are oestrogen receptor positive, while 30% are negative. The study encompassed 337 patients operated at the Kruševac Regional Centre in the period from 1 January 2011 to 31 December 2013. The patients were classified into four groups according to their hormonal status, after which all groups were tested for certain parameters. All patients had histopathological findings and diagnosis confirmation. Patients with a determined receptor status (329) were divided into four groups depending on the steroid (oestrogen and progesterone) receptor status. Data was analysed with regard to hormonal sensitivity with the patients split into two subgroups: hormone-sensitive and hormone-insensitive. Our results show that 67.65% of the carcinoma were ER+/PR+, 9.19% ER+/PR-, 0.59% ER-/PR+, and 21% ER-/PR-17.21, while 18 women (5.34%) were not tested. Our low percentage of ER-/PRof 17.21% is probably due to the fact that only 18 (5.34%) of the patients were younger than 40. The average share of ER+/PR+, found in our study to be 67.65% goes to over 90% in postmenopausal patients, while the share of ER-/PRamounts to 33.33% in younger patients. The study of oestrogen and progesterone receptor status relative to the patient's age showed that the percentage of patients with ER/PR positive status increases statistically significantly with age and the percentage of hormone insensitive cancers declines, but this decline is not statistically significant.

Gene Methylation in Circulating Cell-Free DNA from the Blood Plasma as Prognostic and Predictive Factor in Breast Cancer

Gene Methylation in Circulating Cell-Free DNA from the Blood Plasma as Prognostic and Predictive Factor in Breast Cancer

Targeted Agents for HER2-Positive Breast Cancer: Optimal Use in Older Patients.

The human epidermal growth factor-2 (HER2) gene is overexpressed in 15-20 % of all breast cancers. HER2 overexpression is a predictive factor in breast cancer and is associated with high rates of disease recurrence and death in the absence of adjuvant systemic therapy. With the advent of HER2-directed therapies, there has been a significant improvement in the outcome of HER2-positive (HER2+) breast cancer in all clinical settings. Patients aged >65 years remain under-represented in most clinical trials. Existing literature suggests that older patients with HER2+ disease derive a similar benefit from anti-HER2 therapies as do their younger counterparts, in both adjuvant and metastatic settings. Cardiotoxicity from HER2-directed therapy is a major concern with older patients, especially in the setting of pre-existing co-morbidities. Older patients need a geriatric assessment before beginning any systemic therapy, to identify patients predisposed to developing toxicity and to plan therapy. Many onco-geriatric tools have been developed to further identify frail patients. In this article, we discuss the most up-to-date clinical data on existing therapies for HER2+ breast cancer in adjuvant, neoadjuvant, and metastatic settings, and their application in older patients. We attempt to highlight clinical benefits and toxicities in this group that may aid clinicians in therapeutic decision making.

Pre-analytics, a national survey of Senonetwork Italia breast centers: Much still to do ahead

IntroductionPre-analytics involves handling and processing of microbiopsy and surgical specimen. It is critical for the preservation of morphology and the integrity of molecular markers, which are paramount as prognostic and predictive factors in breast cancer. Although pre-analytical variables in breast cancer are codified by national and international guidelines, there is currently no data on their actual endorsement in clinical practice among Breast Units (BU). Materials and methodsAn anonymous questionnaire was sent by e-mail by Senonetwork Italia, a no-profit organization representing the multidisciplinary network of BU in Italy. The questionnaire involved twenty-four questions concerning critical issues related to the average time and transport temperature of the samples, monitoring of warm and cold ischemia, average fixation time for biopsies and surgical specimens, inking of the margins, and radiography of the operating sample. ResultsForty-nine of 113 affiliated BU (43%), involved in the management of 44% of all breast cancer treated every year in Italy, answered the questionnaire. More than 90% of the BU reported a biopsy/VABB fixation time between 6 and 24 h. Only 41% of the Centers received the fresh operative sample to be sectioned immediately, 20% used the vacuum method and the sample arrived in the laboratory within 24–72 h. Delay in sectioning the sample was reported in as many as 40% of BU, while hot and cold ischemia time was monitored in only 4.2% and 6.2% of BU, respectively. ConclusionCritical issues on pre-analytics are reported by the majority of dedicated BU in Italy. This represents a major challenge regarding quality of care, and improvements are needed in order to obtain valid and reproducible results of prognostic and predictive factors.

Emerging immune gene signatures as prognostic or predictive biomarkers in breast cancer.

Several multigene assays have been developed to predict the risk of distant recurrence and response to adjuvant therapy in early breast cancer. However, the prognostic or predictive value of current proliferation gene signature-based assays are limited to hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer. Considerable discordance between the different assays in classifying patients into risk groups has also been reported, thus raising questions about the clinical utility of these assays for individual patients. Therefore, there still remains a need for better prognostic or predictive biomarkers for breast cancer. The role of immune cells comprising tumor microenvironment in tumor progression has been recognized. Accumulating evidences have shown that immune gene signatures and tumor-infiltrating lymphocytes (TILs) can be prognostic or predictive factors in breast cancer, particularly with regard to HER2+ and triple-negative breast cancer. In this review, I summarize current multigene assays for breast cancer and discuss recent progress in identifying novel breast cancer biomarkers, focusing on the emerging importance of immune gene signatures and TILs as prognostic or predictive biomarkers.

Prognostic role of Tif1γ expression and circulating tumor cells in patients with breast cancer.

Transcription intermediary factor 1γ (Tif1γ), a ubiquitous nuclear protein, is a regulator of transforming growth factor-β (TGF-β)/Smad signaling. Tif1γ can function as an oncogene and as a tumor suppressor. In the present study, Tif1γ levels were measured in the plasma of patients with breast cancer in order to investigate the association of Tif1γ with overall survival (OS). The results indicated that Tif1γ is an independent prognostic and predictive factor in breast cancer, and thus, a promising target protein for use in diagnostics and patient follow-up. Plasma levels of Tif1γ were measured in samples obtained from 110 patients with operable breast cancer and in 110 healthy volunteers at the Breast Cancer Department of Yangpu Hospital between 2008 and 2016. The association between Tif1γ levels and clinicopathologic parameters, and the OS in a follow-up period of 98 months was evaluated. The prognostic significance was assessed using the Kaplan-Meier method. The levels of Tif1γ were significantly lower in patients with breast cancer compared with healthy controls. The average concentration of 18.40 ng/ml was used to discriminate between Tif1γ-positive (52) and Tif1γ-negative patients (58). Tif1γ-positive patients had a significantly improved OS compared with Tif1γ-negative patients. In the multivariate analysis, Tif1γ was an independent predictor of a favorable OS in a prospective follow-up setting; thus, Tif1γ plasma levels are an independent prognostic factor for patients with breast cancer. These findings support the potential of using measurements of Tif1γ plasma levels to guide breast cancer therapy and monitoring. Further studies are required to validate Tif1γ as an easily detectable, non-invasive prognostic biomarker for breast cancer.

Predictive and Prognostic Impact of Tumor-Infiltrating Lymphocytes (CD8+) In Breast Cancer Treated With Neoadjuvant Chemotherapy

Background and Objectives: the use of neoadjuvant chemotherapy (NAC) in breast cancer induces a pCR in only 30–35% of patients. We can’t depend only on clinical and pathological factors to distinguish the patients who have no chance of a pCR or not. Moreover, the NAC scenario is the perfect setting to study possible changes in TIL levels. Tumor-infiltrating lymphocytes (TIL) (CD) 8+ are essential components of tumor-specific cellular adaptive immunity. However, only few studies have addressed the significance of (CD8+) TIL in patients with breast cancer. Patients and Methods: we assessed the stromal and intratumral TIL, CD+8 in pretreatment core biopsy by immuohistochemistry (IHC) in 45 patients with breast cancer received neoadjuvant anthracyclin and docetaxel chemotherapy. CD8 classified into high or low according to the inter quartile range. Tumors with ≥ 50% intratumoral or stromal lymphocytes were designated lymphocyte predominant breast cancer (LPBC). Results: we found statistically significant correlation with high CD8 and DFS and smaller tumor residual (95% CI, 18.6-22.9; P= 0.01) and (p=0.003) respectively. But there was no significant difference regarding pCR or OS between high and low groups. Conclusion: this study confirmed that the CD8 TIL is an important prognostic and predictive factor in breast cancer.

HIP1 expression predicts outcome in breast cancer patients treated with neoadjuvant chemotherapy

IntroductionHuntingtin-interacting protein 1 (HIP1) binds to inositol and clathrin, which is related to neurodegeneration. Signaling of growth factors receptors through clathrin is one mechanism by which cells regulate intracellular signaling. High levels of HIP1 protein have been observed in breast, colon, kidney, lung, ovarian and prostate cancer and melanoma. MethodsTumor biopsies were obtained from 83 breast cancer patients (p) treated with four cycles of fluorouracil, epirubicin and cyclophosphamide neoadjuvant chemotherapy. Estrogen receptor, progesterone receptor, HER2, cytokeratin 5/6, vimentin and HIP1 were examined by tissue microarray. HER2 was also assessed by chromogenic in situ hybridization and the prognostic and predictive value of HIP1 expression was evaluated. ResultsHIP1 was evaluated by immunohistochemistry (IHC) in 83 p, considered negative if the result was 0, and positive if it was 1, 2 or 3. The result was 0 in 11 p (13.3%), 1 in 40 p (48.2%), 2 in 25 p (30.1%), and 3 in 7 p (8.4%). Negative HP1 was correlated with poorly differentiated tumors (p=0.021) and triple negative tumors (p=0.038). Negative HIP1 was not correlated with response but HIP1 negative was correlated with shorter time to progression (TTP) (p=0.003) and overall survival (OS) (p=0.009). ConclusionsHIP1 could be a prognostic and predictive factor in breast cancer.

Clinicopathological characteristics of oestrogen receptor negative, progesterone receptor positive breast cancers: re-evaluating subsets within this group

AimsThe presence of oestrogen and progesterone receptors (ER, PR) in breast carcinoma is an important prognostic indicator as well as a predictor of likely response to hormonal treatment. Current ambiguity...

Relationship between HER2 Proto-oncogene Status and Prognostic Factors of Breast Cancer in the West of Iran

Breast cancer is a very common health problem in Iranian women. The HER2-neu gene is a transmembrane receptor tyrosine kinase with homology to members of the EGF receptor family. The aim of this study was to investigate the association between HER2-neu oncogene status with prognostic factors of breast cancer in Kermanshah province, Iran. Relationship between HER2-neu and prognostic factors of 130 cases of breast cancer were evaluated during two years in Imam Reza hospital in Kermanshah, Iran. Data were analyzed using descriptive statistics and the T-test and Mann-Whitney U non-parametric test using SPSS 19. The mean age for the patients was 46.0±8.0 years, all being female. Among the predictive factors for breast cancer were family history, stage of disease, involvement of the lymphovascular system, number of involved lymph nodes in axillaries, grading and hormone receptor status with HER2-neu oncogene had direct correlation and between factors, tumor location, patient age and histological characteristics and HER2-neu oncogene had no significant relationship. We found significant correlation between HER2 with ER and PR and also HER2 with ER, PR negative. HER2-neu is risk factor that can be a good prognostic and also predictive factor. For these reasons, we recommend that it be evaluated for all types of BC.

Manejo de las muestras para test inmunohistoquímicos, moleculares y genéticos en el cáncer de mama

Molecular and immunohistochemical analysis of tissue samples are useful tools to establish prognostic and predictive factors in breast cancer. The efficiency of these techniques is based on a correct management of surgical specimens which includes pre-analytic controls such time of ischemia, appropriate fixation, gross manipulation and paraffin embedding. It is also important the right selection of tumor representation for study submission. The accuracy of all these steps will affect in the optimal result of the immunohistochemical and molecular test applied.

Breast Carcinoma; Human Epidermal Growth Factor Receptor-2 (HER-2) and Grading Correlation

Introduction: Overexpression of Human Epidermal Growth factor Receptor-2 (HER-2) is one of the most important prognostic and predictive factors of breast cancer, observed in 25% - 30% of breast carcinoma patients leading to poor prognosis and feasible anti HER-2 antibody drugs. The objective of this study was to evaluate the HER-2 frequency in target population and its correlation with histologic grade as well as tumor pathology, estrogen receptor (ER) and P53 in our patients. Methods: A total of 300 cases (all female) aged 24- 80 year, were randomly selected from patients who were admitted in two of the Tehran University of Medical Sciences affiliated centers (Emam Khomeini Cancer Institute and Shariati hospital) over a 2-year period (2013-2014). Assessment of tumors for HER-2, P53, ER, pathological type and histologic grade was performed. HER-2 over expression defined as three plus (+++) in immunohistochemistry (IHC). Results: The mean age was 49.6±11 years. HER-2 over expression was seen in 34% of the patients. Significant correlations were found between HER-2+, P53+ and high histologic grade and ER (P<0.05). However, there was no significant correlation between HER-2 and pathologic type of tumors in our study. Conclusion: Co-expression of several poor prognostic biomarkers in breast cancer (HER-2 +, P53 +, ER- , high grade) may predict more aggressive phenotype, worse disease and lower overall survival in these patients.

Impact of cyclooxygenase-2 over-expression on the prognosis of breast cancer patients.

The aim of this present study was to assess the impact of COX-2 over-expression on breast cancer survival. Non-metastatic invasive breast cancer patients who received adequate loco-regional and systemic treatments were evaluated. Patients' demographic, clinical, pathologic, and treatment-related and survival data were retrieved from their hospital files. COX-2, estrogen/progesterone receptor (ER/PR), HER-2/neu expression and Ki67 index of the tumors were determined immunohistochemically. As the primary objective, COX-2 positive and negative patients were compared in terms of overall (OS), disease-free (DFS) and breast cancer-specific survival (BCSS). Secondary objectives were to assess the independent prognostic factors for survival. In addition, the correlation of COX-2 expression with conventional prognostic and predictive factors of breast cancer was assessed. Two hundred and seventeen patients who underwent adequate breast cancer treatment between November 2004 and December 2013 were included in the study. The median follow-up was 37 months (range: 5-107). Eighty-one (37%) patients were COX-2 positive. OS, DFS, and BCSS were similar in COX-2 positive and negative patients. Ki67 index and age were significantly correlated with COX-2 expression (r=-0.116; p=0.02; r=0.159; p=0.02). PR expression was found to be the only independent factor for predicting OS, tumor size and molecular subtype classification were found to be the only independent factors for predicting DFS, and PR expression was found to be the only independent factor for predicting BCSS. Among the independent predictive and prognostic factors of breast cancer, COX-2 over-expression was only correlated with Ki67 index and age.