Neu Status Research Articles

Her-2/neu Status in Syrian Women with Breast Carcinoma: A Syrian Cohort Study of more than 10000 Cases

Her-2/neu Status in Syrian Women with Breast Carcinoma: A Syrian Cohort Study of more than 10000 Cases

Her-2/neu Oncogene Amplification by Fluorescence In Situ Hybridization and Protein Overexpression on Immunohistochemistry in Breast Cancer.

To investigate the concordance and discordance between the test results of Her-2/neu by immunohisto-chemistry (IHC) and flourescence In Situ hybridization (FISH) in breast cancer cases. Descriptive cross-sectional study. Department of Histopathology, Dr. Ziauddin Hospital, Karachi, from 2011 to 2016. Forty-three specimens of invasive ductal carcinoma of breast were evaluated for grade and Her-2/neu status using IHC and FISH methods. Concordance and discordance between their results was determined. There is 100% concordance between FISH and IHC in cases scoring 0, 1+ (negative) and 3+ (positive) immunostaining. Tumour cases scoring 2+ immunostaining showed amplification in 69.2% cases. All grade-I tumours were non-amplified on FISH, while most of the grade-III tumours showed Her-2/neu amplification on FISH. There is significant association of Her-2/neu IHC with tumour grade and FISH (p<0.05). A fairly high proportion i.e. 69.7% of cases showed Her-2/neu gene amplification. There was high concordance between Her-2/neu testing on IHC and FISH, (Kappa co-efficient 0.466, p <0.001). Her-2/neu amplification increases with increasing grade of breast cancer. A high proportion of Her-2/neu gene amplified cases indicates aggressive disease in that area and need for FISH testing on large scale, which is the gold standard for equivocal cases on immunohistochemistry.

Low serum 25-hydroxy vitamin D levels are associated with aggressive breast cancer variants and poor prognostic factors in patients with breast carcinoma.

This study was conducted to assess the serum 25-hydroxy (OH) vitamin D levels in patients with breast cancer compared to healthy controls and to identify its association with aggressive breast cancer phenotypes. Serum 25-OH vitamin D levels of 78 breast cancer patients and 78 matched healthy controls were estimated using ELISA. The cases and controls were matched with respect to age, menopausal status, parity, weight, height and co-morbidities. Prognostic factors like grade of tumour, hormone receptor status, HER2 neu status and lymphovascular invasion were compared with 25-OH vitamin D levels. The mean serum 25-OH vitamin D levels of cases were significantly lower compared to the controls (22.33 ± 8.19 vs. 37.41 ± 12.9 ng/mL; p = 0.0001). Patients with higher grades of tumour, non-luminal types of breast cancer and breast cancers with estrogen receptor negativity had significantly lower serum 25-OH vitamin D levels than their opposing groups. Patients with excellent and good Nottingham's prognostic Index (NPI) had significantly higher serum 25-OH vitamin D levels than the moderate and poor NPI groups. Newly diagnosed breast cancer patients have significantly lower serum 25-OH vitamin D levels than healthy controls. Lower level of serum 25-OH vitamin D correlates with aggressive breast cancer phenotypes.

P-Glycoprotein Expression in Indian Breast Cancer Patients with Reference to Molecular Subtypes and Response to Anthracycline-Based Chemotherapy-a Prospective Clinical Study from a Developing Country.

Chemo-resistance is an important factor determining the response of tumor to neoadjuvant chemotherapy (NACT). Our study was aimed to determine the role of P-glycoprotein (P-glyp) expression as a predictor of response to NACT in locally advanced breast cancer (LABC) patients with special reference to molecular subtypes. Sixty cases of locally advanced breast cancer (LABC) were subjected to trucut biopsy and the tissue samples were evaluated immunohistochemically for P-glyp, ER, PR, and Her 2 neu status. Pre- and post-NACT P-glyp expression was correlated with clinical response (using WHO criteria after three cycles of CEF regimen) and molecular subtypes. The change in the P-glyp expression before (pre-) and after (post-) NACT was statistically significant with higher stage (p = 0.02), hormonal negative molecular subtypes (p = 0.01), and poor clinical response (p = 0.01). Pre-NACT-positive P-glyp expression is associated with higher stage and hormonal negative molecular subtypes and poor clinical response. The increased expression of P-glyp induced by NACT likely explains the concept of acquired chemo-resistance and may prove as an intermediate checkpoint in determining chemo-sensitivity for further treatment so that additional doses of ineffective chemotherapy may be avoided in non-responders translating into better patient safety.

Hypermethylated LATS2 gene with decreased expression in female breast cancer: A case control study from North India

BackgroundLATS2, a presumed tumor suppressor gene located on chromosome 13q11–12 is involved in cell growth related activity like regulation of cell cycle at G1/S. The reduced expression of LATS2 has been reported in many tumors; including tumors of Breast, which is to the best of our knowledge has not been studied in north Indian female breast cancer population. ObjectiveHere, we looked upon the expression pattern and methylation status of the LATS2 gene in north Indian female breast cancer cases to further strengthen its role as a tumor suppressor gene and more importantly as a cancer biomarker. MethodsmRNA expression level was determined by real time PCR in 140 Breast cancer patients, Protein expression was studied by Immunohistochemistry and Promoter methylation was studied by Methylation specific PCR. All findings were correlated with clinicopathological features. ResultsLATS2 mRNA expression was remarkably downregulated in 67.85% (95/140) cases. The expression of Large Associated Tumor Suppressor 2 at protein level was also absent in 67.85% (95/140) cases. The absence of LATS2 protein strongly correlated with promoter hypermethylation where 91 out of a total of 107 hyper methylated cases showed absence of protein (91/107, 85%). The absence of LATS2 protein was strongly significant with HER2 neu status (0.01), TNM staging (0.009) and Molecular subtype (0.024). ConclusionThe decreased expression in breast cancer seems to be associated with hypermethylation of LATS2 promoter regions. Further LATS2 as a tumor suppressor can be recognized as a promising Biomarker in Breast cancer pathogenesis. Though, further studies, targeting larger sets of breast cancer population are required to establish LATS2 as a promising biomarker.

Potential diagnostic role of circulating MiRNAs in breast cancer: Implications on clinicopathological characters

BackgroundCirculating miRNAs are stable in body fluids and resembles their levels in cancer tissue/cells. They have been expressed in many cancers among them is breast cancer. Authors aimed to investigate the expression levels of three circulating oncomiRNAs (miRNA-21, miRNA-222 and miRNA-373) in serum samples as a minimally non-invasive method for early detection of breast cancer, and study their relation with clinicopathological characters. MethodsMiRNAs expression levels were determined using quantitative real-time polymerase chain reaction (qPCR) in serum samples from three groups: primary breast cancer patients (n = 137), benign breast lesion patients (n = 60), and healthy individuals as control group (n = 38). Statistical analyses were carried out using SPSS. ResultsSignificant differences were observed between the expression levels of the studied miRNAs in the investigated groups, as their median levels were increased in breast cancer patients followed by benign group patients then the healthy individuals. MiRNA-373 reported the highest diagnostic efficacy as compared to miRNA-21 and miRNA-222 with high area under the curve (AUC equals 0.987). The relation between tested miRNAs and clinicopathological factors revealed significant difference with clinical stages and histological grades. Level of miRNA-21 and miRNA-373 were statistically significantly higher in invasive duct carcinoma (IDC) as compared to non-IDC. Similarly, their levels were increased in lymph node metastasis (P < 0.01). MiRNA-222 and miRNA-373 were significantly increased in positive PgR and positive Her-2/neu status, respectively. ConclusionAssessment of miRNAs in serum samples can be applied as minimally non-invasive markers for early detection of breast cancer, and as discriminator between different clinicopathological characters.

Correlation of tumor size and immunohistochemistry status with lung metastasis in carcinoma breast

Background: Breast cancer is common cancer among females in rural India and is rapidly catching up to cervical cancer in rural India. Metastasis can occur after the initiation of treatment or at the time of diagnosis. The stage at initial presentation and underlying biology of the tumor has an impact on prognosis and metastasis of the tumor. The objective of the study was to study the correlation between tumor size and lung metastasis and to find the correlation between ER, PR status, and lung metastasis.Methods: This study was conducted in 82 patients with breast carcinoma coming to the department of the general surgery and oncology at Government Stanley Medical College and Hospital. Details of cases and full history obtained. Routine blood investigations were done. Tumor size is evaluated by clinical examination and imaging. For all patients, core needle biopsy is done to confirm the diagnosis and receptor status. IHC status of the tumor is obtained from the pathologist. Presence of lung metastasis documented by CECT chest.Results: In this study, the prevalence rate of lung metastasis in carcinoma breast patients is 9.75% Total number of Carcinoma Breast are 82, in which lung metastasis is seen in 8 cases and CECT chest is normal in 74 patients. The prevalence rate of lung metastasis in ER-positive patients is 9.90%. The prevalence rate of lung metastasis in ER-negative patients is 10.81%. The prevalence rate of metastasis in PR positive patients is 9.52%. The prevalence rate of metastasis in PR negative patients is 10%. Of 34 cases with HER-2 positive status 3 patients presented with lung metastasis with a prevalence rate of 8.82%. Of 48 cases with HER-2 negative status 5 cases presented with lung metastasis with a prevalence rate of 10.42%.Conclusions: In this study prevalence of lung metastasis in carcinoma breast is 9.75%. There seems to be no correlation between ER, PR and HER-2 neu status and lung metastasis. There is also no correlation between clinically T2 and T3 tumors and lung metastasis. Whereas clinically T4 tumors seem to have a higher incidence of lung metastasis.

Determination of HER-2/neu gene Status by Chromogenic in Situ Hybridisation Assay on Borderline (2+) Immunohistochemistry Cases in Patients with Invasive Breast Carcinoma: An Experimental Study on Preserved Tissue

HER-2 (also known as HER-2/neu) is a member of the epidermal growth factor (EGF) receptor family. The amplification of oncogene HER-2 is presented in 20 to 30% of breast cancers and results in an increase of the protein expression. HER-2 over expression has also been shown to correlate with poor prognosis. It is associated with poorly differentiated high grade tumors with lymph node involvement, greater risk of recurrence and relative resistance to some types of chemotherapy. The receptor is however a target for treatment with anti HER-2 antibody trastuzumab (Herceptin). Immunohistochemistry analysis for HER 2 scoring is subjective, requires trained personnel and expertise. One of the main concerns with IHC is that there is evidence of significant inter-observer variation in the assessment of staining, which can lead to misclassification of HER2 status. Chromogenic in situ hybridization (CISH) testing is sensitive and specific in detecting HER-2/neu gene amplification. Direct evaluation of gene amplification using CISH assay is a reliable method for routine diagnostic evaluation of HER2/neu status in breast cancer patients, especially in specimens showing 2+ IHC score. This observational experimental study was carried out in the Department of Pathology, Bangabandhu Sheikh Mujib Medical University, Dhaka, during the period of July 2014 to June 2015, The aim of this study was to assess HER-2 expression accurately in equivocal immunohistochemistry (2+) invasive breast cancer cases by Chromogenic in situ hybridization (CISH) and to associate the findings of CISH assay with the histologic prognostic and predictive factors (eg: tumor size, regional lymph node metastases, tumor grade and type. A total of 20 archival paraffin tissue blocks and IHC slides with IHC score 2+ for HER-2 were included in this study. All the slides were reviewed. CISH assay was done on section from archival paraffin block.CISH assay showed amplification of the HER-2 neu gene in 30% of cases. Majority (60%) was nonamplified. In two cases the results were unsatisfactory for interpretation. The differences were not statistically significant (p&gt;0.05) among three groups (amplified, nonamplified and unsatisfactory) regarding the baseline characteristics (age and sex) with CISH. All the results of CISH assay in association with tumor size, tumor grade and lymphnode metastasis were not statistically significant. HER-2 / neu status is the one of the most important prognostic and predictive factor. It is a target for treatment with anti HER-2 antibody trastuzumab (Herceptin). Detection of HER-2/ neu status by IHC may sometimes be difficult and inaccurate, specially in IHC score 2+ cases. Based on the findings of the study, CISH can be considered a useful, simple and reproducible method for detecting HER-2/ neu gene amplification in cases with borderline (2+) immunohistochemistry score , and patients may be benefited from Trastuzumab therapy.

EVALUATION OF RECEPTOR STATUS IN CARCINOMA BREAST

Background/Objective: In Indian population, there has been a fairly steady and large increase in the incidence of breast cancer over the past several decades and its management requires complex multidisciplinary approach to increase overall survival rate. As data for incidence of luminal subtypes is Indian patients is absent which will indicate the prognosis of the patient, this study was taken up to study the incidence of receptor status and hence luminal subtypes in Indian patients. This study was conducted in the Department of Genera Methods: l Surgery at Chigateri General Hospital and Bapuji Hospital attached to J.J.M. Medical college, Davangere. 30 patients with diagnosed carcinoma breast were selected according to the inclusion criteria and tumor tissue was sent to pathology lab to determine the Estrogen Receptor (ER), Progesterone Receptor (PR), Her 2 Neu status and Ki67 index. 50% are above 50 years (post- menopausal) and 90% of the patie Results: nts are females. Histopathological examination showed that 76.6% were diagnosed with IDC and majority of patients are present in stage IIB and stage IIIA . In our study we observed luminal A subtypes comprised of 23.33% of cases where as luminal B subtypes comprised of 20% of cases, Majority of cases i.e. 33.33% were basal like / triple negative with poor prognosis .Her 2 Neu amplied cases comprised 23.33% of total study population which is similar to western population. The receptor status is very different on out study population of Indian patient Conclusion: s as compared to the western population and hence it is recommended that ER, PR, Her 2 Neu and Ki67 index analysis should be performed routinely on all breast cancer patients which changes the treatment plan and impact on the overall survival rate

Evaluation of Estrogen and Progesterone Receptors and Her-2 Expression with Grading in the Fine-needle Aspirates of Patients with Breast Carcinoma.

Background:There has been a limited literature with regards to comparison between the pre-operative hormonal/Her-2 neu assessment by immunostaining on fine-needle aspiration (FNA) versus core needle biopsies (CNBs) and their correlation with grading of breast carcinoma.Materials and Methods:Two hundred fifty FNAs and 201 CNBs from 252 patients with breast carcinoma were subjected immunocytochemical/histochemical (ICC/IHC) staining along with the grading by the Robinson cytologic and modified Scarff-Bloom-Richardson scoring systems, respectively. Depending on the material adequacy, IHC was also performed on cell blocks. Sensitivity, specificity, and predictive values of ICC were calculated. The kappa statistics was performed to see the power of the study. Cytologic versus histologic gradings were compared and analysed by percentage analysis.Results:Sensitivity of ICC on FNAs for ER, PR, and Her-2neu was 49%, 28.8%, and 46%, respectively, while specificity was 84.5%, 90.6%, and 86.6%, respectively, with a fair agreement on kappa statistics. Her-2neu positivity on CNB versus FNA had a moderate agreement. Her-2neu staining of 3+ was seen in most of the Grade-2 tumours on FNA.Conclusions:Fairly reliable results on grading and hormonal/Her-2neu status are possible when ICC is performed on qualitatively superior FNA material. This is particularly useful in the management of patients in certain settings like inoperable cases.

Development of a novel prognostic score for breast cancer patients using mRNA expression of CHAC1.

To develop a prognostic score for primary breast cancer patients integrating conventional predictors and the novel biomarker CHAC1 to aid adjuvant chemotherapy decisions. A prognostic score for overall survival was developed using: conventional predictors from a dataset of 1777 patients and the weight of CHAC1 mRNA expression from an independent dataset of 106 patients using multivariate Cox regression. The new score includes: CHAC1 mRNA expression, age, tumor size, HER2 neu status, lymph node status and degree of malignancy. Using a cut-off value of11 score points, 10-year survival was 82% in low-risk (n=34) and 43% in high-risk patients (n=72). The addition of CHAC1 resulted in 16% reclassification. Including CHAC1 in prognostic prediction may aid (and change) personalized treatment selection.

Immunohistochemical and Clinicopathological Factors Associated with Axillary Lymph Node Metastasis in Breast Cancer Patients of Northern Pakistan

Background: Breast cancer is the most common type of tumors in Pakistani women, with axillary lymph node (ALN) positivity reported to be one of the most important prognostic factors.This study shows the distribution of various clinical and pathological variables including age, tumor size, grade, histologic subtype, and hormone receptor status among Pakistani women with and without ALN metastasis.Materials and Methods: A total of 245 cases of primary breast cancer from Northern Pakistan were analyzed in this study. Their clinical, pathological and immunohistochemical parameters, including estrogen receptor (ER), progesterone receptor (PR) and Her-2/Neu status, were extracted from previous histopathological reports and stratified based on the occurrence of ALN metastasis. Results: Occurrence of ALN metastasis was significantly different between older age patients above 50 years and younger age patients age &lt;50 years [χ² (1, N=245) =14.6, p&lt;0.001]. There was an increased number of metastases in large sized tumors &gt;5cm in size (80%, n=60), [χ² (2, N=245) =23.1, p&lt;0.001] and tumors with higher nuclear grade III (78.4%, n=40), [χ² (1, N=245) =5.1, p=0.02]. ALN metastasis was inversely associated with expression of estrogen receptor [χ² (1, N=245) =12.5, p&lt;0.001], and progesterone receptor [χ² (1, N=245) = &lt;0.001, p=0.99], while it was directly associated with Her-2/Neu expression [χ² (1, N=245) =5.63, p=0.01]. Conclusion: In Pakistani women, ALN metastasis was significantly associated with older age, tumor size, and high-grade tumors showing Her2/Neu expression and was inversely associated with ER, PR expression in breast tumors.

Discordance of the estrogen receptor and HER-2/neu in breast cancer from primary lesion to first and second metastatic site.

BackgroundHormone receptor and HER-2/neu discordance between the primary lesion and first metastasis has been reported. This study was performed to determine further biomarker discordance rates between the first and subsequent metastatic breast cancer lesions.MethodsWe performed a retrospective review of paired biomarkers from primary breast cancers compared to first reported and subsequent metastases from 103 patients with breast cancer. The estrogen receptor (ER), progesterone receptor (PR), and HER-2/neu status were reported at all three time points. In addition, hormone, cytotoxic, and targeted treatments were recorded for primary and metastatic disease, and survival was determined.ResultsBetween the primary and first metastases, discordance rates for ER, PR, and HER-2/neu were 15.8%, 33.7%, and 14.3%, respectively. There was discordance between the first and second metastases for the ER receptor in 18.8%, PR receptor in 19.8%, and HER-2/neu in 10.7%. Overall, there was discordance between the primary tumor and either the first or second metastases for ER in 27.7%, PR receptor in 40.7%, and HER-2/neu in 19.6% of cases. Discordance of either ER or PR affected survival, with worse survival experienced by those patients with all three hormone receptors remaining negative, and intermediate survival reported for those with discordant tumors (ER χ2=14.27, p=0.0008; PR χ2=11.31, p=0.0035). There was no difference in survival for patients whose HER-2/neu tumors were discordant.ConclusionThis study demonstrated that continued metastatic disease evolution may be associated with different tumor biology and that studies of metastatic lesions appear warranted, especially if targeted therapy is an option.

Abstract OT2-03-01: NRG oncology/NSABP B-51/RTOG 1304: A phase III superiority clinical trial designed to determine if chest wall and regional nodal radiotherapy (CWRNRT) post mastectomy (Mx) or the addition of RNRT to breast RT post breast-conserving surgery (BCS) will reduce invasive cancer events in patients (pts) with positive axillary (Ax) nodes and convert to ypN0 after neoadjuvant chemotherapy (NC)

Abstract Background: This phase III post-NC trial evaluates if CWRNRT post Mx or whole breast irradiation (WBI) with RNRT after BCS significantly reduces the invasive breast cancer recurrence-free interval (IBC-RFI) rate in pts presenting with positive Ax nodes that are pathologically negative after NC. Secondary aims are OS, LRRFI, DRFI, DFS-DCIS, and second primary cancer, as well as comparing RT effect on cosmesis in reconstructed Mx pts. Correlative science studies examine RT effect by tumor subtype, molecular outcome predictors for residual disease pts, and predictors for the degree of reduction in loco-regional recurrence. Methods: Clinical T1-3, N1 IBC pts with positive Ax nodes (FNA or core needle biopsy) complete ≥8 wks of NC (anthracycline and/or taxane). HER2-positive pts receive anti-HER2 therapy (tx). After NC, BCS or Mx is performed with a sentinel node biopsy (≥2 nodes) and/or Ax dissection with histologically negative nodes. ER/PR and HER2 neu status before NC is required. Pts receive required systemic tx. Radiation credentialing with a facility questionnaire and a case benchmark is required. Randomization for Mx pts is to no CWRNRT or CWRNRT and for BCS pts to WBI or WBI+RNRT. Statistics: 1636 pts to be enrolled over 5 yrs with definitive analysis at 7.5 yrs. Study is powered at 80% to test that RT reduces the annual hazard rate of events for IBCR-FI by 35% for an absolute risk reduction in the 5-yr cumulative rate of 4.6%. Intent-to-treat analysis with 3 interim analyses at 43, 86, and 129 events, with a 4th/final analysis at 172 events will occur. Accrual as of 6/13/16 is 356. Pt-reported outcomes focusing on RT effect will be obtained from 736 pts before randomization and at 3, 6, 12, and 24 months. Contacts: Protocol: CTSU member website https://www.ctsu.org. Questions: NRG Oncology Pgh Clin Coord Dpt: 1-800-477-7227 or ccd@nsabp.org. Pt entry: OPEN at https://open.ctsu.org or the OPEN tab on CTSU member website. Support: U10 CA-2166; -180868, -180822; -189867; Elekta. Citation Format: Mamounas EP, Bandos H, White JR, Julian TB, Khan AJ, Shaitelman SF, Torres MA, Vicini FA, Ganz PA, McCloskey SA, Paik S, Gupta N, Li XA, DiCostanzo DJ, Curran, Jr WJ, Wolmark N. NRG oncology/NSABP B-51/RTOG 1304: A phase III superiority clinical trial designed to determine if chest wall and regional nodal radiotherapy (CWRNRT) post mastectomy (Mx) or the addition of RNRT to breast RT post breast-conserving surgery (BCS) will reduce invasive cancer events in patients (pts) with positive axillary (Ax) nodes and convert to ypN0 after neoadjuvant chemotherapy (NC) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT2-03-01.

HER2/neu Testing In 432 Consecutive Breast Cancer Cases using FISH and IHC - A Comparative Study.

The development of trastuzumab, a HER-2/neu targeted monoclonal antibody resulted in significant improvements in clinical response and survival in HER-2/neu gene amplified group of patients. Thus, accurate assessment of HER-2/neu status becomes critical. Fluorescence In Situ Hybridization (FISH) and Immunohistochemistry (IHC) are the most commonly used methods for this purpose and specific recommendations exist with regard to the concordance to be observed between the two tests. Here, we report and evaluate the concordance rate between FISH and IHC for HER-2/neu status in breast cancer specimens. Archival paraffin blocks of tumour tissue from 450 patients of breast cancer were analyzed for Her-2/neu status using FISH and IHC. There was a highly significant concordance between the results of FISH and IHC assays in HER-2/neu status assessment in invasive breast cancer cases. There were inverse associations between the expression of Oestrogen Receptors/Progesterone Receptors (ER/PR) and HER-2/neu amplification. Although, IHC gave significant concordant results with FISH in determining HER-2/neu status, its subjective grading system precludes its use as a gold standard. FISH should always be used to determine true gene amplification when the IHC results are equivocal.

Pattern of distant metastasis in molecular subtypes of carcinoma breast: An institutional study.

Molecular subtypes of carcinoma breast show a particular pattern of distant metastasis, the knowledge of which can help to diagnose and intervene early in the course of the disease. The aim of this study was to investigate and establish an association between the molecular subtypes of carcinoma breast and the pattern of distant metastasis. Single arm, retrospective study. Totally 400 patients of carcinoma breast (Stage I and II) were selected who were treated between January 2010 and December 2013. All these patients were treated with the standard treatment protocol for breast cancer. The estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2 (HER-2) Neu status, and Ki-67 were done, and patients were classified into luminal A/B, HER-2 enriched, luminal/HER-2, and triple-negative subtypes. All patients were followed up until December 2015, and the pattern of local failure as well as distant metastasis was correlated with the molecular subtypes. A total of 143 patients developed distant metastasis and local recurrence. Bone was the most common site of metastasis overall. It was the most common type of metastasis in luminal A/B (53.3%) and luminal-HER (57.1%). Brain metastasis was most common in HER-2-enriched subtype (30.3%), whereas liver was the most common site of metastasis in HER-2-enriched subtype (45.45%). The incidence of brain metastasis was comparatively lower in luminal A/B subtype. Local recurrence was most common in HER-2-enriched subtype. The results were statistically significant for lung metastasis and local recurrence (with P = 0.004 and 0.047, respectively). A strong association exists between the molecular subtypes and the site of distant metastasis in breast cancer which can be used for greater vigilance to detect site-specific distant metastasis beforehand.

Utility of gene expression signature in treatment decision of breast cancer

Breast cancer is the most common cancer and a leading cause of cancer-related mortality in women worldwide. About 1.7 million women were diagnosed with breast cancer in 2012 and 6.3 million women were alive with breast cancer in the previous five years (1,2). Despite modern therapeutic interventions, the 5-year survival rate of breast cancer has improved only marginally and its recurrence is observed in more than 50% of the patients (3,4). Treatment failure and recurrence of breast cancer can be attributed to multiple factors which are difficult to predict for a particular patient (5). Genomic tests such as Oncotype DX, MammaPrint, miRNAs and other molecular and clinico-pathological markers are often employed for guiding therapeutic decisions (6-13) but it is difficult to say which test is reliable. Subtyping of breast cancer is largely based on estrogen/progesterone receptor (ER/PR), and human epidermal growth factor receptor 2 (HER2)/neu status and the most aggressive form is considered to be triple negative breast cancer (TNBC) (14), the drug resistance and recurrence rate of which is extremely high (15-17). Most alarmingly, TNBC has recently been found to be prevalent in as high as 74% of premenopausal women below 35 year of age (18). However, there exists no TNBC-specific therapeutic target yet.

Immunohistochemical Staining of Estrogen Receptor and Human Epidermal Growth Factor Receptor 2 in Carcinoma Breast in Bangladeshi Women

Introduction: Breast cancer is the most common cause of cancer death among women. Estrogen Receptor (ER), Progesterone Receptor (PR) and human epidermal growth factor receptor 2 (Her-2/ neu) status are used as an important prognostic marker for breast cancer.Objectives: The aim of this study was to evaluate ER and Her-2 in breast carcinoma among Bangladeshi women and to co-relate with other prognostic parameters.Materials and Methods: The study was carried out in a tertiary level hospital in Bangladesh during the period of January 2010 to December 2011. Total 100 histologically proved breast carcinoma cases were included in the study. Immunostaining for ER and Her-2/neu were carried out. Quick scoring of ER and expression of Her-2/neu were correlated with histomorphological parameters.Results: Among 100 cases 93 were ductal carcinoma and 07 were non ductal. Among all, 38% show ER positive (score- 3-8) while 62% are ER negative (score 0-2). Her-2/neu was over expressed in 30%, 22% were borderline and 48% were negative. There were inverse relationship between ER positivity and Her-2/neu overexpression. ER positivity was related with lower histological grade, while Her-2/neu overexpression was related with higher histological grade.Conclusions: ER positivity in Breast carcinoma patients in Bangladesh is lower in comparison to western literature while Her-2/neu overexpression rate is quite high like other Asian countries.Journal of Armed Forces Medical College Bangladesh Vol.11(1) 2015: 7-13

The Study of HER-2/neu, ER/PR Expression Using Immunohistochemistry (IHC) in the Iraqi Breast Cancer

Background: Breast cancer is the most common cancer in woman that originates from the uncontrolled growth of abnormal breast cells. According to the Iraq Cancer Registry 2009, breast cancer ranks as the first between the ten common cancers in Iraq and there is a wide tendency to increase the rate of breast cancer in earlier age group. Estimation of estrogen (ER) and progesterone (PR) receptors status as well as human epidermal growth factor receptor 2(Her-2/neu) serve as specific guidance to select the patients whose benefit from endocrine therapy and provide prognostic information. The study aimed to assess the expression of ER/PR hormone receptor and Her-2/neu in breast cancer patients and correlation with various Clinicopathological aspects as a predictive biomarker.Method: The current study was performed from the period between Jan 2015-Feb 2015 in Department of Oncology that referred to Baghdad Teaching Hospital in the Medical City. Routine staining hematoxylin and eosin (H&amp;E) for histopathological examination and immunohistochemistry (IHC) test for ER, PR and Her-2/neu expression was conducted in all cases.Results: This study includes total 30 cases of breast cancer. The age of patients were between 29-65 years with 47± 9.8 (mean ±SD). Majority of tumors are invasive ductal carcinomas represented 23(76.7%).There are significant differences between different scores were observed in IHC test for Her-2/neu status and showed 8(26.7%) out of 30 cases were positive expression.The ER and PR expression status was strongly associated and demonstrated in 21(70%) of cases.The most commune subgroup was Her-2/neu+, ER/PR+ seen in 10(33.3%) out of 30 breast cancer patients.Conclusion: HER-2/neu is positively expressed in about 26.7% of breast cancer cases.The study of ER, PR status showed higher rates of positive expression70% and was strongly associated. Using IHC examination the Her-2/neu+, ER/PR+ subgroup indicates the most common subtype 10 (33.3%) compared to other tumor subtypes in breast cancer.

A new digital classification schema to detect treatment variances and enable value-based payment reforms.

28 Background: Value based payment reforms which improve the outcome to cost ratio (paying for outcomes not for services) require detailed information on both elements. Although the digitalization of medicine via the EHR may facilitate data collection, the imprecise ICD9 and ICD10 schemas hinder analysis (eg: all breast cancers are ICD9 174.9). A more precise classification schema that accounts for biologic variances to allow analysis (and reduction) of treatment variances is needed. Methods: We have developed a digital classification (COTA Nodal Address) based on known clinically relevant prognostic variables. (eg: breast cancer variables include stage, tumor size, hormone status, her2 neu status, etc.). The digital classification also accounts for therapy status (neoadjuvant vs adjuvant, etc.) and line (1st or 2nd treatment, etc.). Results: Using breast cancer as an example, there are &gt; 2975 unique CNA phenotypes that encompass prognostic and treatment status variables. However, in a series of 1204 patients in a community setting only 114 CNAs have been utilized, suggesting biologic disequilibrium. Two phenotypes accounted for the top 25% of cases, 6 for the top 50% and 16 for the top 75%. Early stage, small tumor, hormone receptor positive were most common. The CNA classification uncovered treatment variances among patients with similar phenotypes. In an ongoing episodes of care payment program, young breast cancer patients with early stage, good performance status, hormone positive, her2 neu negative, very small tumors (with similar extended attributes) received varying adjuvant treatment strategies (hormone alone 46% , non-anthracycline 35%, anthracycline chemotherapy 4%, observation 1%). Conclusions: Unlike ICD9/10 systems, a digital classification schema that precisely segregates cancers into unique cohorts based on complete biologic characteristics can rapidly identify behavioral variances at scale that drive differences in outcomes and costs. Using the breast cancer model, we have noted demographic disequilibrium in cancer presentations (potentially a factor of both biology and screening practices) and major variances in treatment strategies (with impact on outcomes/ costs).