HER2 Research Articles

Resistance to Trastuzumab.

Simple SummaryTrastuzumab is a humanized antibody that has significantly improved the management and treatment outcomes of patients with cancers that overexpress HER2. Many research groups, both in academia and industry, have contributed towards understanding the various mechanisms engaged by trastuzumab to mediate its anti-tumor effects. Nevertheless, data from several clinical studies have indicated that a significant proportion of patients exhibit primary or acquired resistance to trastuzumab therapy. In this article, we discuss underlying mechanisms that contribute towards to resistance. Furthermore, we discuss the potential strategies to overcome some of the mechanisms of resistance to enhance the therapeutic efficacy of trastuzumab and other therapies based on it.One of the most impactful biologics for the treatment of breast cancer is the humanized monoclonal antibody, trastuzumab, which specifically recognizes the HER2/neu (HER2) protein encoded by the ERBB2 gene. Useful for both advanced and early breast cancers, trastuzumab has multiple mechanisms of action. Classical mechanisms attributed to trastuzumab action include cell cycle arrest, induction of apoptosis, and antibody-dependent cell-mediated cytotoxicity (ADCC). Recent studies have identified the role of the adaptive immune system in the clinical actions of trastuzumab. Despite the multiple mechanisms of action, many patients demonstrate resistance, primary or adaptive. Newly identified molecular and cellular mechanisms of trastuzumab resistance include induction of immune suppression, vascular mimicry, generation of breast cancer stem cells, deregulation of long non-coding RNAs, and metabolic escape. These newly identified mechanisms of resistance are discussed in detail in this review, particularly considering how they may lead to the development of well-rationalized, patient-tailored combinations that improve patient survival.

Metachronous Contralateral Breast Cancer in Ahmadu Bello University Teaching Hospital, Zaria, Northwestern Nigeria.

Breast cancer is the most frequent cancer of women. Metachronous contralateral breast cancer (MCBC) is a cancer in the contralateral breast after 6 months of the initial diagnosis of the first breast cancer. It is an important public health issue because of an increased incidence of a primary breast cancer and improved survival. There is a paucity of data in the Northwestern region of the country. The study was to document the incidence, the method of detection, clinicopathological features, and the treatment of MCBC in our hospital. It was a 7-year prospective study from January 2011 to December 2017. Patients who had treatment for nonmetastatic breast cancer, American Joint Committee on Cancer (AJCC) Stages 1-111, were followed up. Those that developed MCBC were studied. Age, the method of detection, stage at presentation, pathological types, hormone receptor status, and treatment were documented. Data obtained were analysed using SPSS version 21.0. Results were presented as simple percentages and charts. Of 1285 women with nonmetastatic breast cancer, 47 had MCBC (incidence of 3.7%); 30 (63.8%) were aged 21-50 years; 23 (48.9%) detected by self-breast examination; 13 (27.7%) by clinical breast examination; seven (14.9%) by mammography; and four (8.5%) by breast ultrasound scan. Fourteen (29.8%) were AJCC stage I; 23 (48.9%), stage II; seven (14.9%), stage III; and three (6.4%), stage IV. Thirty-nine (83%) were invasive ductal carcinoma; 22 (50.0%) were estrogen receptor/progesterone receptor (ER/PR) positive, human epidermal receptor (HER)-2 neu negative; nine were (20.5%) ER/PR and HER-2 neu positive; six (13.6%) were ER/PR negative, HER-2 neu positive, whereas seven (15.9%) were triple negative. Forty-three (91.5%) had modified radical mastectomy and 19 (40.4%) had cytotoxics. With an average of six cases in a year, MCBC is common in our hospital. Majority (63.8%) were young. The commonest method of detection was by self-breast examination. Majority (78.3%) presented at an early stage. Most (91.5%) still had modified radical mastectomy.

Dosimetric evaluation of cardiac and left anterior descending artery dose in patients with left-sided breast cancer treated by different techniques of hypofractionated adjuvant radiotherapy after breast conservative surgery

The aims: to dosimetrically evaluate the dose to the heart and left anterior descending artery in left-sided early breast cases using different techniques.
 Materials and methods: Prospective observational/analytical study done in cases of left-sided BCS referred for adjuvant RT in 54 patients. Patients who underwent left-sided BCS (breast conservative surgery), patients aged between 18- and 75 years performance status ECOG 0-2, histological confirmed DCIS, Invasive Breast Cancer-Stage 1, 2, 3, patients without any evidence of metastatic disease Irrespective of hormonal receptor and HER-2 neu status are included in the study.
 Results: All the 3 parameters for LAD showed the highest doses with 3DCRT and lowest with VMAT. Thus our study favoured VMAT (p<0.01) as the planning technique to achieve the least doses of LAD. However, for the heart, there was no statistically significant difference between 3DCRT and IMRT (p=0.349) for the average mean dose (Gy). On the other hand, there was a statistically significant difference between 3DCRT Vs VMAT and IMRT Vs VMAT (95 % CI, p<0.01), again favouring VMAT as the choice of planning technique. The average heart max dose(Gy) and average heart V20(%) showed statistically significant benefits with VMAT (p<0.01). There was a statistically significant benefit (p<0.000) with VMAT for both LV parameters. At the same time, there was a statistically significant benefit in terms of ipsilateral lung dose with VMAT(p<0.000), the dose to the right lung, right breast and favoured 3DCRT (p<0.01). PTV95 % (Gy) by 3DCRT, IMRT, and VMAT in our study is 41.01, 41.96, and 41.76, respectively. Though the difference between the 3 techniques seems meagre, there was a statistically significant difference (p<0.012) favouring IMRT.
 Conclusion: We conclude that using the VMAT technique in radiotherapy for left-sided breast cancer can significantly reduce radiation doses to the heart and LAD, potentially reducing cardiac risk. For all patients, the cardiac doses are considerably decreased for all dose levels without compromising the dose coverage to PTV, which is an advantage over IMRT and 3DCRT

Clinicopathologic Correlation of CD44 + /CD24 - Expression in Breast Cancer: a Report from Tertiary Care Medical University in India.

CD44 + /CD24 - phenotype has been associated with stem cell-like characteristics with enhanced invasive properties, radiation resistance, and with distinct genetic profiles suggesting a correlation to adverse prognosis in western literature. The aim of this study was to study CD44 + /CD24 - phenotype as an adverse prognostic marker in Indian breast cancer patients. N = 61 breast cancer patients included in a tertiary care facility in India were evaluated for receptor studies (estrogen receptor ER, progesterone receptor PR, Herceptin antibody Her2 neu receptor, CD44 & CD24 stem cell markers). CD44 + /CD24 - phenotype was statistically related to adverse factors like estrogen and progesterone receptors non-expression, her 2 neu expression, and triple-negative breast cancer. Of the 39 patients with ER-ve status, 33 (84.6%) were found to have CD44 + /CD24 - phenotype and 82.5% of all the CD 44 + /CD24 - patients were ER negative (p = 0.001). Thirty-four (75.5%) of the PR-ve patients showed the CD44 + /CD24 - phenotype, and of all the CD 44 + /CD24 - patients, 85% of were PR negative (p = 0.006). Thirty-six (75%) of Her-2-Neu + ve were CD44 + /CD24 - . Approximately 90% of the Her 2 Neu patients expressed CD44 + /CD24 - and 76.9% of all the triple-negative patients were found to be CD44 + /CD24 - expression (p = 0.001). CD44 + /CD24 - had a significant association with adverse prognostic factors like stage of disease, hormonal receptor status, and molecular subtypes in Indian breast cancer patients like the Western data.

Molecular Classification of Breast Carcinoma in a Tertiary Hospital of India: the Recent Trends.

Breast cancer is a heterogeneous disorder with various subcategories of different cellular compositions, molecular alterations, and clinical behaviour and is dependent on numerous factors like grade, size, and hormonal receptors which influence the overall prognosis and response to the treatment. This study was done to determine the frequency of estrogen receptor (ER), progesterone receptor (PR), and Her2 neu positivity in breast cancer patients, further classifying them into their molecular types (luminal A, B, Her2 neu, and triple-negative) and studying their association with histological subtypes, lymph node status, and other epidemiological parameters. This was a 5-year retrospective study done on 314 patients. All relevant clinical data including the age, sex, and lymph node status along with the histological type and grade of the tumour were recorded, and immunohistochemical evaluation of Her2 neu, ER, and PR receptors was done. The results showed that ER was the most predominant immunomarker, followed by PR, with an inverse relationship between ER, PR, and Her2 neu. Among the molecular subtypes, luminal B showed the maximum prevalence followed by triple-negative and Her2 neu subtype. The least frequency was shown by luminal A. Our study concluded that molecular subtyping of breast carcinoma plays an important role in determining the prognosis, recurrence, and treatment. Increased expression of luminal B subtype can be correlated due to the advancing age of the patients.

Metastatic Trends in Breast Cancer According to Molecular Subtypes, Estrogen Receptor, Progesterone Receptor and Human Epidermal Growth Factor Receptor 2neu Status

Background : Breast cancer molecular subtypes have been established a close relationship with site specific metastasis, disease prognosis, selection of therapy and response to therapy. This study is the evaluation of primary tumor molecular determinants and its clinical outcome in association with metastatic behavior of breast cancer. Material and Methods: This prospective study was included 221 patients of breast cancer registered in the department between January 2016 to December 2018. Based upon hormonal status, patients with breast cancer were categorized into four groups i.e. luminal (ER+, PR+, HER 2neu-), HER 2neu enriched (ER-, PR-, HER 2neu+), triple positive (ER+, PR+, HER 2neu+) and triple negative (ER-, PR-, HER 2neu-). Metastatic sites were divided into skeleton and visceral (lung, liver, and brain). The study data was compiled using Microsoft Excel sheet and Chi-Square test was used to assess the association between categorical variables. P value less than 0.05 was considered as statistically significant. Results : The mean age of the patients was 48.21±11.4 years (ranging from 22 to 80 years). About 36.7% and 24.9% patients were diagnosed as stage III A and stage II B respectively. Majority of patients were categorized as luminal (43%), followed by 24%, 17.2% and 15.8% as triple negative, triple positive and HER 2neu enriched respectively. Metastasis to bone following breast cancer was observed in majority i.e. 11.8% cases. Lung and liver metastasis observed in 6.3% cases each whereas brain metastasis was observed in 0.9% cases only. The higher proportions of TNBC cases metastasized to bone (22.6%), liver (7.5%), lung (7.5%) and brain (1.9%). The association between metastasis and hormonal status was statistically highly significant for bone metastasis (p<0.05). Conclusion : Breast cancer molecular subtypes have been related to considerable distinction in pattern of distant spread. Bone is the most predominant site of metastases followed by liver lung and brain. Luminal and HER 2 neu enriched subtypes having greater propensity for visceral metastasis where as TNBC predominantly show bone metastasis in this study. Keywords: Breast cancer, molecular subtypes, site-specific metastasis

The Association between The Patient’s Age Groups with Stage, Grading, and Molecular Subtype of Breast Cancer

In 2020, Global Cancer Observatory reported breast cancer incidence was 11.7% and mortality was 6.9%, most presenting a late-stage and delaying diagnosis. The study aimed to assess the breast cancer clinicopathologic characteristics according to the age groups. The research was conducted on 98 Medical Records from Bethesda Hospital Yogyakarta. The variable data were analyzed by univariate and the association between variables were analyzed with binary logistic regression with odds ratio and 95% confidence interval. The presentation of age groups ≤ 30 years (1,02%), 31-40 years (12,24%), 41-50 years (25,51%), 51-60 years (46,94%), and ≥ 61 years (15,31%); right breast (48,98%) and left breast (51,02%); stage I (3,06%), II (28,57%), III (55,10%), dan IV (13,27%); ductal type of breast cancer (89,80%) and others (10,20%); molecular subtype luminal A (43,88%), luminal B (14,29%), HER-2 neu enriched (29,59%), and basal-like/triple-negative (12,24%). There wasn’t any association between age groups and stages (p=0.368). There was an association between age groups and molecular subtype (p=0.013, OR 2.993 CI95% 1.239-7.230). Conclusions: The commonest clinicopathologic characteristic of breast cancer patients were in the age group 51-60 years, left breast, high stage, ductal type, and luminal A. Hormone receptors in breast cancer expressed more common in patients ≤50 years.

Role of dynamic and parametric whole-body FDG PET/CT imaging in molecular characterization of primary breast cancer: a single institution experience.

The aim of this pilot study was to assess the role of dynamic whole-body PET and parametric imaging in the biological characterization of primary breast cancer. In total 24 histologically proven primary breast cancer lesions in 21 consecutive patients were retrospectively analyzed. Each patient underwent 18F-fluoro-deoxyglucose whole-body dynamic PET-CT before any treatment. Dynamic PET images were acquired in the list mode for a total duration of 70 min. The reconstructed parametric imaging generated Patlak plot-based 'Slope' and 'Intercept' images, from which parametric indices ki and DV were obtained. The standard uptake value (SUV) metric was also obtained by summing the last few frames of the dynamic study. ki, distribution volume (DV) and SUV were correlated with the histological tumor grade, biomarkers [hormone receptors and human epidermal growth factor receptor 2 (HER-2) neu expression] and molecular subtypes (A, B and C) as well as with tumor size, regional nodal metastases and distant metastases. The mean ki was found to be significantly higher in grade III than II lesions (P = 0.005), HER-2 neu positive status (P = 0.04) and molecular subtype B (P = 0.04) as well as in greater than T1 lesions(P = 0.0003 and P = 0.04, respectively) and node-positive lesions (P = 0.009). Though mean ki was not found to be significant for the hormone receptors status (P = 0.08), it showed the best correlation compared to the other parameters (P = 0.8 for DV and P = 0.1 for SUV). Spearman's correlation test, area under the curve (AUC) and mismatch percentage also revealed ki to predict tumor grade (AUC, 0.95; r = 0.7; P = 0.0001), HER-2 neu status and molecular subtypes (AUC, 0.81; r = 0.49 and P = 0.01) along with the hormone receptors status (AUC, 0.83; r = 0.32; P = 0.1). The mean DV failed to show any association with any of the biological or anatomical staging parameters. Though ki was found to be comparable to that of SUV in almost all the assessed parameters, it appeared to be better for predicting hormone receptors status even though both parameters were not statistically significant. Our initial observation in a small cohort of breast cancer patients suggests that ki is promising in stratifying primary breast cancer lesions according to the tumor grade and biological characteristics.

Elucidation of HER2/neu and Wilms’ tumor 1 immunohistochemical expression in endometrial carcinomas regarding the diagnostic and prognostic significance

Objective To confirm HER2 neu and Wilms’ tumor 1 (WT1) immunohistochemical expression in endometrial cancer and illustrate its possible diagnostic and prognostic significance in various clinicopathological parameters that both physicians and pathologists may find therapeutically valuable. Materials and methods A total of 50 formalin-fixed and paraffin-embedded tissue specimens were acquired and prepared for this investigation from the archival pathology files of Al-Hussein and Al-Zahraa University Hospitals between 2017 and 2020, after obtaining the informed consent and approval of the local ethical committee. The patient’s medical records and histopathologic data such as tumor size, myometrial invasion depth, lymph node invasion, histologic type of tumor, clinical presentation, and International Federation of Gynecology and Obstetrics stage were assessed using hematoxylin-eosin for all sections that were re-evaluated by HER2/neu and WT1 antibodies immunohistochemically. Results Positive HER2/neu and WT1 expressions were frequently associated with a worsening condition in patients with endometrial carcinomas (ECs) with a higher grade, stage, and nonendometrioid carcinoma type, reflecting the prognostic relevance of HER2/neu and WT1 expressions, especially in aggressive EC forms. Follow-up and more genetic concordance between EC subtypes could improve the predictive value of HER2/neu and WT1 expression in EC. For advanced endometrial malignancies, tailored chemotherapy may be valuable. Conclusions HER2/neu-positive and WT1-positive immunohistochemical staining results are generally coupled to ECs in their advanced forms, which have a higher grade, stage, and nonendometrioid carcinoma type, reflecting their prognostic implications, especially in aggressive EC types. However, additional validation is required before enrolling this panel in clinical settings, which could improve the value of prediction of HER2/neu and WT1 immunohistochemical markers in ECs. Moreover, targeted chemotherapy for aggressive endometrial cancers can be beneficial.

Frequency of HER-2 NEU Receptor Positivity and its Relationship with Estrogen Progesterone Receptors in Patients of Breast CA

Background: Carcinoma breast is the commonest malignancy of females all over the world and second leading cause of death due to cancer among females. In Pakistan it is more common at a young age contrary to the West where it is more common in old age (after 60 years). The objectives of this cross sectional study were to determine the frequency of HER-2/neu receptor over-expression and its association with some of the features of breast cancer like patient age, ER/PR status, tumour size, histological grade and axillary lymph node involvement. Methods: This study was conducted at Surgery ward unit 2, Fatima Memorial Hospital, Lahore, from June 2015 December 2015. Study included all patients with breast cancer admitted in Surgery unit 2 of FMH, Lahore for Modified Radical Mastectomy (MRM). The resected specimens were sent to histopathologist for immunohistochemical (IHC) studies (HER-2/neu receptor and ER/PR) and detailed histopathological analysis including tumour subtype, size, histological grade and involvement of axillary lymph nodes. Patients refusing HER-2/neu receptor immunohistochemistry were excluded from the study. Name, age, sex, other relevant data, detailed history and clinical examination findings and results of investigation were recorded. Data was analyzed with SPSS version 10. Results: This study included 50 patients of breast cancer having modified radical mastectomy (MRM). Age distribution ranged from 45-61 years with a Mean±SD of age 52.2±4.3 years. 30 out of 50 patients (62.5%) were >52 years, while 20 patients out of 50 (40%) were ≤40 years of age. The HER-2/neu receptor status was found positive in 30 patients (60%) and negative in 20 patients (40%) of the total cases While, it was significantly associated with tumour size (p<0.05) and negative ER/PR status (p<0.05). Conclusion: Due to high prognostic significance and frequency in Pakistani females with breast cancer, HER-2/neu receptor should be checked in all patients with breast cancer so that the positive cases should have herceptin therapy and benefit from anthracycline based chemotherapeutic agents which can improve survival in these patients. Keywords: Breast carcinoma, HER-2/neu, ER/PR

Study of multiparametric MRI morphology in breast carcinoma and its correlation with TNBC

Introduction: Pre-operative breast MRI for the patient with newly diagnosed BC increases the sensitivity of characterising the tumours , tumour size, multifocality-multicentricity, dermal and lymph node involvement. It assesses treatment response and guides treatment planning. Predicting biological subtype using IHC (ER, PR, Her2 neu) has become the standard of care. Very few studies focussing on the comparison between multiparametric MRI and molecular subtypes are available.

EGFR and HER2/NEU immunoexpression in ovarian neoplasms in Bundelkhand Region

Introduction: Ovarian Cancers account for the greatest number of deaths from malignancies of female genital tract and it is the fifth leading cause of cancer fatalities in women. Surface epithelial tumours are the most common, followed by germ cell tumours. Objective: To analyse the expression of EGFR and HER 2neu using Immunohistochemisty in different Ovarian tumours with special reference to surface Epithelial tumours. Material and Methods: 52 cases of different ovarian tumours were studied. Cases included total abdominal hysterectomy with bilateral saphingoophorectomy, oophorectomy, and cystectomy specimens. Expression of EGFR (ErbB1) and HER2-neu (ErbB2) was determined by immunohistochemical reactions performed with the Super SensitiveTM IHC Detection system by the BiogenixTM. Tests were performed according to the instructions of each kit. Results: The mean age of presentation for epithelial tumours was found to be 42.48 years. For malignant epithelial tumours mean age of presentation was found to be 51.1 years. EGFR positivity was found in 28.57 % of surface epithelial ovarians tumours, and HER2/neu positivity was seen in 20% of surface epithelial ovarian tumours. As far as malignant serous papillary adenocarcinoma is concerned, we found 33.3% positivity for HER2/neu and 50% positivity for EGFR.

Immunohistochemical profile of carcinoma breast and its association with clinicopathological features: a single institutional experience

Background: Breast cancer is a systemic disease which has different biological subtypes with vast natural history, clinical presentation, various pathological types and molecular features which has impact on prognostic profile and outcome. Present study aims to evaluate correlation of receptor status (ER, PR and HER 2neu) with other tumor characteristics.Methods: The present study was a prospective observational study of 50 breast cancer patients and was conducted from January 2020 to June 2021 in surgical unit of the department of general surgery at MDM hospital attached with Dr. S. N. medical college, Jodhpur, Rajasthan.Results: Most common age group was 41-50 years in 38% cases. Majority of patients were females (49, 98%). The 88% cases had invasive duct carcinoma. ER, PR and HER 2neu positivity had statistically significant correlation with age (p<0.0001), histological grade (p<0.0001) and tumor size (p=0.04). HER 2neu had statistically significant negative correlation with ER and PR (p<0.05).Conclusions: Immunohistochemistry (IHC) markers (ER, PR, HER 2neu) are positively correlated with increasing age, tumor size, tumor grade and positive axillary lymph nodes, also there is statistically significant correlation between HER 2neu overexpression and hormone receptor (ER, PR) negativity in study population.

A Novel Subset of Triple-Negative Breast Cancers with Unique Histology and Immunohistochemical Expression.

Background & Objective:Triple-Negative Breast Carcinoma (TNBC) is characterized by an absence of estrogen receptor, progesterone receptor and HER2 neu expression, with distinct molecular, histological and clinical features, aggressive clinical course and a poor prognosis. The objective was to evaluate the expression of Cytokeratin5/6 (CK 5/6), Epidermal Growth Factor Receptor 1 (EGFR 1), E-cadherin and Androgen receptor in tissue sections of TNBC. Methods:All modified radical mastectomy samples received negative for the three markers were subjected to further studies with CK5/6, EGFR 1, E- cadherin and Androgen receptor staining. The clinical and pathological data were tabulated and statistically analysed using the Chi-square test, and cross-tabulation was done to assess the correlation between these markers.Results:Of 94 samples classified as TNBC, 31 (33%) were positive for CK 5/6, 47 (50%) for EGFR, 32 (34%) for E Cadherin and Androgen receptor, respectively. We had one positive patient for all four markers, 13 patients were negative for all four. Thirty-five cases were positive for only one marker, 32 were positive for two markers, and 13 were positive for three markers. Analysis revealed certain interesting patterns, namely - E cadherin was the most common isolated marker expressed in our cohort of TNBC with 15 of 35 positives. Conclusion:This study highlights the presence of a unique subtype of TNBC, which are negative for all the four markers studied here, with unique histomorphology of absent tumour necrosis and stromal lymphocytic infiltration being unique.

Abstract ES8-3: Refining axillary management after neoadjuvant chemotherapy - what does the evidence support

Abstract The surgical management of the axilla in patients with operable breast cancer has undergone significant evolution over the past 25 years. Axillary lymph node dissection (ALND), the undisputed standard since the end of the 19th century, has largely been replaced by sentinel lymph node biopsy (SLNB) in most patients with clinically negative axilla with considerable reduction in axillary morbidity. Neoadjuvant chemotherapy (NAC) has been increasingly used in early-stage breast cancer, particularly in patients with triple-negative and HER-2 neu positive tumors. Rates of sterilization of involved axillary lymph nodes with NAC in appropriately selected patients have been steadily increasing with the adoption of more effective NAC regimens. Adoption of SLNB after NAC has lagged behind that of upfront SLNB. Recent data support the feasibility and accuracy of the procedure after NAC in patients who present with clinically negative axilla. Although the accuracy of SLNB is lower after NAC in patients who present with documented involvement of the axilla, identification and removal of the previously biopsied axillary lymph node(s) in addition to performing SLNB (“targeted axillary dissection”) greatly improves the accuracy to levels equivalent to those with upfront SLNB. Citation Format: P Mamounas. Refining axillary management after neoadjuvant chemotherapy - what does the evidence support [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr ES8-3.

STUDY OF CORRELATION OF INFLAMMATORY CELL INFILTERATION SCORE WITH TUMOR GRADE, NODAL STATUS, ER, PR, HER-2 NEU STATUS IN PATIENTS OF STAGE 2 AND 3 BREAST CANCER IN A TERTIARY CENTER, KOLKATA

Breast Cancer is the most common cancer in women in India and constitute one–third of women’s cancers and is second reason of mortality after lung carcinoma.[1] It is the most commonly diagnosed malignancy in most cities in India, and 2nd most common cancer in females in the rural areas. As the disease burden and mortality rate is very high, evaluation of several parameters that influence survival rates among women with breast cancer may help design early detection, predict the prognosis and frame a suitable line of treatment.[2] The link between inflammation and cancer was first suggested in 1863.[3] Chronic inflammation is known to increase the risk of cancer development, such as colon cancer in inflammatory bowel diseases.[4] There is good evidence that the development of cancer and its progression are dependent on a complex interaction of the tumour and the host inflammatory response.[5] Aim: This study aims to correlate the relation of inflammatory cell infilteration with tumour staging, nodal status, ER, PR, HER-2 NEU status of breast cancer. Material and Method: The proposed study was a cross sectional study with mostly prospective observation and with some retrospective observation, included 74 patients of stage II and stage III breast carcinoma who underwent MRM in Cancer Institute from 2017-2018. The various clinical and histopathological prognostic parameters along with inflammatory cell infilterate score in invasive breast carcinoma patients were studied and correlated. The inflammatory cell infilterates was assessed according to Klintrup-Makinen (K-M) criteria. It is scored on 4 point scale where score 0 defined no increase in inflammatory cell infilterate, score 1 defined as mild or patchy increase ,score 2 denoted as prominent inflammatory response with some cancer cell destruction and score 3 as florid cup like response. Further it is classified as low group score (score 0-1)and high group score (score 2-3) .[6] Result: There was significant association between inflammatory cell infiltrate score and grade of tumor (p=0.0005) (TABLE 1) .58.1% ,54.1% and 37.8% of the cases were ER, PR and Her-2/neu positive respectively. ER negative tumors (74.19%) were showing statistically significant (p= 0.01) association with high inflammatory cell infilterate score (ie. Score 2 and 3). Similarly PR negative tumors (64.7%) were showing statistically significant association (p= 0.04) with high inflammatory cell infilterate score. No such correlation was found between between HER-2 /NEU status and nodal involvement with inflammatory cell infilterate score (TABLE 3). Keywords: Breast cancer, Invasive ductal carcinoma, ER , PR , HER-2/Neu ,grade of tumor, Nodal status, inflammatory cell infilterate score.

Epidemiological Profile and Clinicopathological Correlates of Triple Negative Breast Cancer Patients at Regional Cancer Centre

Background: Breast Cancer is the most common cancer among woman worldwide. In India breast cancer remains the leading cause of both incidence and mortality. Triple negative breast cancer is more difficult to treat as it does not respond to hormone therapy medicines or medicines that target receptor proteins (like HER 2 Neu). It is crucial for the physician to know the status of the disease as the patient can be subjected to a whole new avenue of treatment. The present study was done to assess the epidemiological profile and clinicopathological correlates of patients of triple negative breast cancer. Material and Methods: This retrospective study was carried out in Acharya Tulsi Cancer and Research Institute located in the state of Rajasthan, Bikaner, India, among Ca Breast patients presenting to Medical Oncology, Radiation Oncology and Surgical Oncology outdoor & indoor from April 2016 to March 2017. Out of the total 1017 patients of carcinoma breast 957 were included in this Study. Exclusion criteria was non availability of ER, PR, HER2 neu status reports because of various reasons like affordability. Out of the total 957 patients 249 were found to be triple negative. Statistical analysis was done using IBM SPSS version 21. Results: Mean age of the patients was 46±11.23 years. Out of total 249 patients of triple negative breast carcinoma, 91 (%) were found to have had clinical staging I and II (Early stage) and 158 (%) patients were found to have clinical staging III & IV (Late Stage). Mean size of the tumor was 3.6±1.94cm. 151 (60.6%) were pre-menopausal, 103 (41.4%) and 12 (4.8%) patients had positive family history. All of or patients diagnosed to have Ductal type of carcinoma. Lympho-vascular invasion was seen in 51 (20.5%) patients and High grade Histological Grading was seen in High Grade 169 (67.9%) patients. 172 (69.1%) undergone MRM (Modified Radical Mastectomy) and BCS was done in 74 (29.7%) patients. After comparison of triple Negative Breast Cancer with non-triple Negative Breast Cancer, lower age, later stages (III and IV), pre-menopausal status and high grade (on histology) were significantly more in negative type of Ca breast. Occurrence of early Menarche (< 13 Years) and history of OC pills used was almost equal in both the groups. Conclusion: Triple Negative Breast Cancer was found to present at an earlier age and more in pre – menopausal women. Such patients presented with a higher histological grade of tumor and late stage of presentation. There was no statistically significant association between TNBC and age of menarche, use of OC pill, previous exposure to radiotherapy and positive family history in first degree relative.

COMPARISON OF CLINICOPATHOLOGICAL PARAMETERS WITH HISTOLOGICAL AND MOLECULAR CLASSIFICATION OF BREAST CANCERS

BACKGROUND: This is a retrospective study of 60 cases, to detect the expression of ER, PR, HER2neu, CK5/6 and Ki67 proliferation index in breast carcinomas by immunohistochemical method and to determine the newer molecular classication. Few patients have recurrence inspite of being diagnosed under the category of low risk and few do well in the high risk group which can be attributed to the molecular level differentiation. AIM: The aim of this study is to categorize the patients under molecular classication, and to compare the clinicopathological parameters with it and to denote the signicance of targeted therapy. MATERIALS AND METHODS: A retrospective study of detecting the expression of the above said markers in modied radical mastectomy specimens received at a tertiary care centre during the period from January 2015 to June 2018. A total of 60 cases which included 30 of IDC NST and 30 cases of special variants were selected for immunohistochemical analysis. RESULTS: Out of the 60 cases studied, the most common was found to be the luminal A type comprising 37% and the least common was the luminal B and hybrid types each comprising 8%. The most common grade for HER2 was Grade III (50%). The association of histological grade with the molecular classication was statistically signicant with the p value of 0.01. Basal type (56%) had the highest incidence of N3 stage. ER, PR, HER2 neu, CK5/6 expression and proliferation index with Ki67 had a statistically signicant association with the molecular classication. High proliferation index (>14%) with Ki67 was noted in Luminal B, Basal and Hybrid types. 78% of the total 60 cases were alive and healthy. One death was reported in HER2, Hybrid and Basal types. The negative kappa value obtained while studying the agreement between the histopathological and molecular classication, indicates that the agreement is worse than chance and hence the importance of molecular classication is substantiated for the targeted therapy.

Are c-erb B2 and UGCG Reliable Immunohistochemical Markers Of Canine Mammary Carcinomas?

In this study, we aimed to correlate c-erb B2, UGCG expressions and tumor size in canine mammary tumors. The material of this study consisted of tissue samples of mammary carcinomas taken from ten female dogs brought to our department between 2012-2020. Avidin-Biotin Peroxidase method was used as an immunohistochemical method. All canine mammary tumor cases were immune positive for c-erb B2 and UGCG reactions. We detected membranous and cytoplasmic c-erb B2 immune positive staining in the neoplastic epithelial cells. Reactions were moderate to strong in severity. We observed strong dark brown cytoplasmic ceramide glucosyltransferase staining in the cytoplasm of neoplastic epithelial cells. We found that the increase in the number of c-erb B2 and UGCG immune positive cells paralleled the tumor size. In conclusion, the increase in the number of c-erb B2 and UGCG positive cells in direct proportion to the tumor size, which is an important diagnostic parameter in canine mammary tumors, made us think that c-erb B2 and UGCG could be reliable immunohistochemical markers in the diagnosis of canine mammary tumors. In addition, these markers must be evaluated comprehensively in line with different cancer diagnosis parameters.

The Utility of SOX2 and AGR2 Biomarkers as Early Predictors of Tamoxifen Resistance in ER-Positive Breast Cancer Patients.

Background Despite the undeniable benefit of tamoxifen therapy for ER-positive breast cancer patients, approximately one-third of those patients either do not respond to tamoxifen or develop resistance. Thus, it is a crucial step to identify novel, reliable, and easily detectable biomarkers indicating resistance to this drug. Objective The aim of this work is to explore SOX2 and AGR2 biomarker expression in the tumor tissue of ER-positive breast cancer patients in combination with the evaluation of serum AGR2 level of these patients in order to validate these biomarkers as early predictors of tamoxifen resistance. Methods This study was conducted on 224 ER-positive breast cancer patients. All patients were primarily subjected to serum AGR2 levelling by ELISA and their breast cancer tissue immunostained for SOX2 and AGR2. After 5 years of follow-up, the patients were divided into 3 groups: group 1 was tamoxifen sensitive and groups 2 and 3 were tamoxifen resistant. Time to failure of tamoxifen treatment was considered the time from the beginning of tamoxifen therapy to the time of discovery of breast cancer recurrence or metastases (in months). Results SOX2 and AGR2 biomarkers expression and serum AGR2 level were significantly higher in groups 2 and 3 in comparison to group 1, while the relationship between Her2 neu expression and Ki67 index in the 3 different groups was statistically nonsignificant. Lower SOX2 and AGR2 expression and low AGR2 serum levels in the studied patients of groups 2 and 3 were significantly associated with longer time-to-failure of tamoxifen treatment. According to the ROC curve, the combined use of studied markers validity was with a sensitivity of 100%, specificity of 96%, PPV 96%, and NPV 100% (p < 0.001; AUC: 0.984). Conclusions Integrated use of SOX2 and AGR2 biomarkers with serum AGR2 assay holds a promising hope for their future use as predictive markers for early detection of tamoxifen resistance in ER-positive breast cancer patients.