Indian Breast Cancer Patients Research Articles

Validation of Navigator-Assisted Hypofractionation (NAVAH) Program Survey to Aid American Indian Breast Cancer Patients.

Flores, Laura E. PhD*; Sargent, Michele RN†; Draeger, Beth RN‡; Petereit, Daniel G. MD†,§; McClelland, Shearwood III MD∥,¶ Author Information

Prevalence of BRCA1 and BRCA2 mutations in an unselected cohort of Indian women with breast cancer.

e13004 Background: Familial breast cancer accounts for 10-15% of breast cancer cases. The prevalence of germline pathogenic mutations in breast cancer susceptibility genes 1 and 2 ( BRCA1/2) among female breast cancer patients remained variable across studies depending on the population/settings studied. The estimate varied between 8-10% of the unselected female breast cancer population. There is a lack of data regarding the prevalence of BRCA1/2 among female breast cancer patients in India. Methods: This prospective observational study included consecutive patients with breast cancer in females, registered at All India Institute of Medical Sciences (AIIMS), New Delhi, India between the period of 1st September 2022 to 25th January 2023(5 months duration). The staging description was done as per anatomic TNM staging according to AJCC 7th edition. Mutation testing was performed in all patients by a standard next-generation sequencing (NGS) assay covering the BRCA1/2 gene. The reflex multiplex ligation by probe amplification method was performed in all cases that were negative by NGS. For patients with detected germline mutations in BRCA1/2, post-test counseling was done, and family screening was also advised. Results: A total of 210 female patients with breast cancer were sequentially included in the study. Young breast cancer (less than 35 years of age) constituted 40 (19.04%) cases. Thirty-eight patients (18.09%) women had a positive significant family history. The median age of the cohort was 46 years (range 18-85 years). Synchronous breast cancer was present in 7 (3.3%) cases. The stage distribution was stage I, 11(5.23%); stage II, 73 (34.76%); stage III, 83 (39.52%); and stage IV, 43 (20.47) %. One hundred and ten patients (52.38%) were hormone-receptor-positive, whereas 66 (31.42%) patients were HER2/neu positive. Triple-negative breast cancer (TNBC) was found in 65 (30.95%) cases. Overall, the prevalence of germline BRCA1/2 mutations was 35/210 (16.6%), which included BRCA 1 and 2 mutations in 22 (10.47%) and 12 (5.71) cases respectively. One case had mutations in both BRCA 1 and BRCA2. Young ( < 35) TNBCs (22 cases/210, 10.47%) have a high propensity for detecting pathogenic BRCA1 mutation (8/22, 36.36%). Conclusions: The prevalence of pathogenic BRCA1/2 in 16.6% of our cohort of unselected consecutive breast cancer patients. It is higher than that reported in the Western population likely due to the younger population and more proportion of triple-negative breast cancer patients in our cohort.

Survival outcomes of BRCA1/BRCA2 mutated breast cancers: Study from a tertiary care cancer centre in India.

e22546 Background: There exists a discrepancy amongst various studies over the years on survival outcomes of BRCA (Breast cancer susceptibility gene) mutated breast cancers. Prevalence of BRCA mutation varies from 10 to 18% among Indian population and there is a paucity of data on the survival outcomes of this population. Methods: This ambispective observational study assessed the survival outcomes of 71 BRCA mutated breast cancer patients, treated with uniform protocol at AIIMS New Delhi between January 2014 to December 2022, using survival analysis and cox regression methods. Results: Amongst the 71 patients, BRCA1 and BRCA2 mutated cases were 52 (73.2%) and 19 (26.8%) respectively. The median age was 39 years (24-63 years) in both the groups. Positive family history for malignancy (BRCA1- 69.2% vs BRCA2- 36.8%) and incidence of Triple negative histology (BRCA1-82.7% VS 36.8%) were more commonly associated with BRCA1 positivity. Eight patients (11.3%) had synchronous cancer, most common being a contralateral breast primary. 4 patients (5.6%) developed metachronous cancer. Eighty percent of patients were premenopausal at presentation. There was no difference in stage at presentation, incidence of synchronous and metachronous cancers across both the groups. Of 71 patients, 18 (25%) and 17 (24%) patients underwent risk reducing mastectomy and risk reducing oophorectomy respectively. Thirty five (49.3%) presented with stage I & II disease, while 28 (34.4%) and 7 (9.9%) presented with stage III and metastatic disease respectively. Forty seven patients (67.1%) received neoadjuvant chemotherapy with pathologic complete response rate of 42.5% which was uniform among both the groups. Over the study period, 10 (14.1%) patients had disease relapse with 7 (70%) being metastatic and 3 patients died of the disease. With a median follow up of 36.9 months, 3-year disease free survival (DFS) was 84.2% (BRCA1: 81.1% vs BRCA2: 93.1%) and overall survival (OS) was 94.7% for both groups. Median DFS and OS were not achieved. BRCA type, receptor status, age and menopausal status were not predictors of survival in our study. Conclusions: In our study population of BRCA1/BRCA2 mutated breast cancer, survival outcomes were comparable to historical cohorts of Indian breast cancer patients. Thus, BRCA mutation positivity doesn’t seem to have any prognostic significance in breast cancer outcome.

Expression of Programmed Death Ligand 1 (PD-L1) in Breast Cancer patients in India and its Correlation with Prognostic Parameters

Background: The PD-1/PD-L1 pathway represents an adaptive immune resistance mechanism that is exerted by tumor cells. The study was conducted to evaluate the expression of PD-L1 in breast carcinoma in India and to find out its correlation with prognostic parameters. Despite numerous studies, there is a lack of literature for such studies in Indian patients. Moreover, the results obtained from these studies have not been uniform. Methods: A hospital-based cross-sectional study was conducted on 150 cases of breast carcinoma. The invasive cancer specimens were assessed for routine microscopy and classified into various histopathological subtypes. Bloom Richardson grading was done. Immunohistochemistry for surrogate molecular classification as well as PD-L1 was performed. PD-L1 expression was then compared with several prognostic parameters such as tumor subtype, tumor grade, surrogate molecular classification and pTNM stage. Data analysis was done using Statistical Package for Social Sciences (SPSS) version 21.0. A P value of <0.05 was considered statistically significant. Results: PD-L1 was positive in 14.67% of patients with score 1 in 6% and score 2 in 8.67% of patients. The PD-L1 expression showed a positive correlation with the tumor of higher grades (grade3). It was significantly higher among IBC with medullary features as compared to IBC-NST, IBC with papillary features and the Lobular type. PD-L1 showed a significant association with surrogate molecular classification as well. Its expression was found to be the highest in Triple negative breast cancer subtype as compared to tumors showing ER/PR positivity (p<0.05). However, there was no significant association between PD-L1 and TNM staging. Conclusion: This study revealed a significant association between PD-L1 several prognostic factors such as higher tumor grade (grade3), Triple Negative breast cancer, and IBC with the medullary pattern subtype. The association between PD-L1 and such prognostic parameters signifies its role in tumor mechanism and makes it a potential target for immunotherapy especially in Triple Negative breast cancer cases which lack specific targeted therapies. Moreover, paucity of literature on PD-L1 in breast cancer patients in India and the data showing conflicting results make this study valuable. Our study shall be helpful in further adding to the knowledge of PD-L1 expression in breast cancer especially in Indian women.

Development and Validation of a Nomogram for Predicting Axillary Lymph Node Metastasis in Breast Cancer

BackgroundAxillary lymph node (ALN) status is a key prognosis indicator for breast cancer patients. To develop an effective tool for predicting axillary lymph node metastasis in breast cancer, a nomogram was established based on mRNA expression data and clinicopathological characteristics. Materials and MethodsA 1062 breast cancer patients with mRNA data and clinical information were obtained from The Cancer Genome Atlas (TCGA). We first analyzed the differentially expression genes (DEGs) between ALN positive and ALN negative patients. Then, logistic regression, least absolute shrinkage and selection operator (Lasso) regression, and backward stepwise regression were performed to select candidate mRNA biomarkers. The mRNA signature was constructed by the mRNA biomarkers and corresponding Lasso coefficients. The key clinical factors were obtained by Wilcoxon-Mann-Whitney U test or Pearson's χ2 test. Finally, the nomogram for predicting axillary lymph node metastasis was developed and evaluated by concordance index (C-index), calibration curve, decision curve analysis (DCA), and receptor operating characteristic (ROC) curve. Furthermore, the nomogram was externally validated using Gene Expression Omnibus (GEO) dataset. ResultsThe nomogram for predicting ALN metastasis yielded a C-index of 0.728 (95% CI: 0.698-0.758) and an AUC of 0.728 (95% CI: 0.697-0.758) in the TCGA cohort. In the independent validation cohort, the C-index and AUC of the nomogram were up to 0.825 (95% CI: 0.695-0.955) and 0.810 (95% CI: 0.666-0.953), respectively. ConclusionThis nomogram could predict the risk of axillary lymph node metastasis in breast cancer and may provide a reference for clinicians to design individualized axillary lymph node management strategies.

Risk factors for breast cancer among adult women residing in rural South Karnataka: a cross sectional study

Background: There’s a steady increase in breast cancer incidence among rural women since rural women are increasingly adopting urban lifestyles, reproductive habits and are also increasingly exposed to similar environmental factors as urban women due to economic development. Objectives was to assess the prevalence of risk factors of breast cancer among women aged 30 years and above residing in a rural South Karnataka Methods: This cross-sectional study was conducted from June 2016 to January 2017 in villages under Ittamadu primary health centre area, Ramanagara Taluk, Ramnagara district. A total of 600 women aged 30 years or above participated in the study. A semi structured questionnaire was administered by interview method after getting written consent. Descriptive statistics and Chi-square test was used. Results: This study revealed that the prevalence of risk factors (reproductive and non-reproductive) of breast cancer among adult women aged 30 years and above was between the least prevalence of 0.7% for family history of breast cancer to highest prevalence of 37.5% for age at menarche at less than 13 years of age. Conclusions: Indian breast cancer patients present with advanced disease stage and have numerous poor prognostic factors, hence knowledge regarding the prevalence of risk factors is necessary to identify how many women are at risk of developing breast cancer as per the established risk factors to promote early detection and timely treatment for improved survival and quality of life of breast cancer patients.

P285 Effect of socio-demographic factors on patient reported outcomes in Indian breast cancer patients

P285 Effect of socio-demographic factors on patient reported outcomes in Indian breast cancer patients

Abstract P2-18-02: Promoter hypomethylation associated upregulation of MEN1 mRNA expression and its correlation with pathological parameters in Indian breast cancer patients

Abstract Background: Breast cancer in the recent years has accounted to be most frequently reported cancer across the globe. Nearly 11.7% of total cancer cases were of breast cancer and 6,84,996 deaths were reported in the year 2020. Multiple endocrine neoplasia type 1 gene that encodes for menin protein is known be involved in numerous signaling pathways and is also reported to show its interactions with histone modifiers. MEN1 is frequently reported to be dysregulated in the cancer including neuroendocrine tumors, lung cancer and melanoma. However, the role of MEN1 in case of Breast cancer has not been well understood. Lifestyle, environmental conditions and ethnicity play crucial role in epigenetic modulation of gene expression. In the current scenario with high increase in number of cancer cases, there is need to develop more personalized course of treatment rather than generalized approach. Thus, discovery of new biomarkers will aid in designing better diagnostic and therapeutic strategy to treat cancer. Aims and Objective: In this study we aim to find MEN1 mRNA expression and its connection with the MEN1 promoter methylation in case of Indian breast cancer patients and to correlate our findings with the pathological parameters of the patients to understand the role of MEN1 gene in breast cancer progression. Material and methods: The ethical approval for the study was procured from Institutional ethical committee of AIIMS,New Delhi and Jamia Millia Islamia, New Delhi. The study comprises of 44 pair of Breast tissue samples including cancer and adjacent normal tissue collected at department of surgical oncology AIIMS, New Delhi and were stored in RNA later and PBS at -80˚C for RNA and DNA extraction respectively. DNA was extracted through PCI (Phenol-Chloroform-Isoamyl alcohol) method and was further confirmed by Agarose gel electrophoresis. TRIZOL method was used to extract RNA from tissue samples and was quantified using nanodrop. Moreover, cDNA synthesis was carried out using Verso cDNA synthesis kit. To investigate the MEN1 mRNA expression, RT- PCR was carried out with LightCycler96 SYBR Green I Master (Roche) using specific primers. To analyze the promoter methylation status of MEN1 promoter region, CT- conversion was done and MS-PCR was performed using Methylation and Unmethylation specific primers. Statistical analysis was done using Graph Pad and SPSS to correlate our findings with clinical parameters. Results: In our study we found 27 out of 44 patients to exhibit up-regulation of MEN1 mRNA in the breast cancer tissue as compared with the normal tisuue. MEN1 promoter unmethylation was detected in 25 out of 44 cases, which revealed its significant correlation with the upregulated MEN1 gene. Further on correlation of our data with the clinical parameters, we found its significant association with the estrogen receptor status and age of menopause of the patients. Conclusion: Our results of the MEN1 mRNA expression study and its association with MEN1 promoter methylation in case of breast cancer suggests the tumorigenic role of MEN1 in breast cancer. Our findings thereby indicate the possible role of MEN1 gene in progression of the disease. Further study on large sample size will aid in better understanding the role of MEN1 gene in Breast carcinoma. Citation Format: Sheersh Massey, Aasif Khan, Asifa Khan, SVS Deo, Syed Akhtar Husain. Promoter hypomethylation associated upregulation of MEN1 mRNA expression and its correlation with pathological parameters in Indian breast cancer patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-18-02.

The association of D-dimer levels with clinicopathological features in Indian breast cancer patients

The association of D-dimer levels with clinicopathological features in Indian breast cancer patients

Breast cancer prediction using supervised machine learning techniques

Breast cancer is one of the most prevalent diseases in India’s urban regions and the second most common in the country’s rural parts. In India, a woman is diagnosed with breast cancer growth every four minutes, and a woman dies from breast cancer sickness every thirteen minutes. Over half of breast cancer patients in India are diagnosed with stage 3 or 4 illness, which has extremely low survival rates; hence, an urgent need exists for a rapid detection strategy. To forecast if a patient is at risk for breast cancer, we utilise the classification techniques of machine learning, in which the machine learning model learns from the previous information and can anticipate on the new information that is generated by the data. To create a model using Logistic Regression, Support Vector Machines, and Random Forests, this dataset was collected from the UCI repository and studied in this study. The primary goal is to improve the accuracy, precision, and sensitivity of all the algorithms that are used to categorise data in terms of the competency and viability of each and every algorithm. Random Forest has been shown to be the most accurate in classifying breast cancer, with a precision of 98.60 percent in tests. The Scientific Python Development Environment is used to carry out this machine learning study, which is written in the python programming language.

A Multi-centric retrospective study into the epidemiological distribution of breast cancer patients in India.

A multicentric private hospital-based retrospective study was conducted to understand the epidemiology of breast cancer in terms of demographics and clinical characteristics (staging and hormone receptor status) at the time of diagnosis. The data for 5,688 female breast cancer patients were collected from the hospital and clinical records of four study centres. All statistical analysis was performed using Microsoft Excel 2016 and R software. Survival was estimated by the Kaplan-Meier method and compared by the log-rank test. A P value of <.05 was considered statistically significant. The mean and median age of the study population was 52.6 (± 12.4) years and 53.0 (range 51-54 across the four centers) years, respectively. About 68% of patients were in the age category of 41 65 years, 17.6% were <40 years old among whom 23.4% of patients reported a positive family history. Most of the patients (66.3%) were diagnosed at an early stage (Stage I and II). The 3-year OS probability was 100%, 97.5%, 94.1%, and 74.7% for TNM Stages I, II, III, and IV, respectively. The 3-year RFS was 95.7%, 95.5%, 84.5%, and 49% for TNM Stages I, II, III, and IV, respectively. The present study highlights the epidemiological distribution of breast cancer patients. It emphasizes the importance of disease awareness among the urban and educated female population as most patients were diagnosed at earlier stages and demonstrated higher OS and RFS than reported in government registries.

Small breast epithelial mucin as a useful prognostic marker for breast cancer patients.

This study aimed to evaluate the clinical utility of small breast epithelial mucin (SBEM) as a prognostic biomarker in an independent patient cohort. The paraffin-embedded tissues and clinicopathological data of 105 patients with breast cancer were collected, and the expression of SBEM in breast cancer samples was detected by immunohistochemical staining. The correlations between clinicopathological variables and the expression of SBEM were analyzed, and its significance as a prognostic indicator for breast cancer patients was determined. Immunohistochemical staining revealed that SBEM was expressed mostly in the cytomembrane and cytoplasm, with markedly increased SBEM expression (≥4 points on staining intensity) observed in 34 of 105 breast cancer tissues (32.4%). Elevated expression of SBEM was found to be significantly associated with larger tumor size (P = 0.002), more frequent lymph node metastasis (P = 0.029), advanced tumor node metastasis stage (P = 0.005), reduced expression of the progesterone receptor (PR) (P = 0.002), and a higher Ki-67 index (P = 0.006). Survival analysis indicated that patients with elevated SBEM expression had worse overall survival (OS) (5-year OS rate: 50.5 vs 93.9% for high and low SBEM expression, respectively, P < 0.001) and disease-free survival (DFS) (5-year DFS rate: 52.8 vs 81.7% for high and low SBEM expression, respectively, P = 0.001) rates than those with low expression of SBEM. Univariate and multivariate Cox analyses demonstrated that elevated expression of SBEM (hazard ratio [HR] = 1.994, 95% confidence interval [CI]: 1.008-3.945, P = 0.047), tumor size (HR = 2.318, 95% CI: 1.071-5.017, P = 0.033), and PR status (HR = 0.195, 95% CI: 0.055-0.694, P = 0.012) were independent predictors of OS in breast cancer patients. Elevated expression of SBEM was associated with both aggressive tumor characteristics and poor survival, indicating its potential as a useful prognostic biomarker for breast cancer patients.

104 (PB-104) Poster - Comprehensive mutation profiling of PIK3CA gene in Indian breast cancer patients

Background: Breast cancer (BC) is the most commonly diagnosed cancer and the leading cause of cancer-related death among women worldwide. It is a complex, heterogeneous disease in which several lifestyle-related and genetic factors are implicated in its pathogenesis. The phosphatidylinositol 3-kinase (PI3 K) is a complex signaling pathway that plays an essential role in cell growth, proliferation, epithelial to mesenchymal transition, survival, invasion, migration, and apoptosis. It is often altered in BC caused by mutations or amplification of the genes encoding the PI3 K catalytic subunits p110α (PIK3CA).

Transcriptomic profiling of Indian breast cancer patients revealed subtype-specific mRNA and lncRNA signatures.

Breast cancer (BC) is one of the leading causes of cancer-associated death in women. Despite the progress in therapeutic regimen, resistance and recurrence of breast cancer have affected the overall survival of patients. The present signatures, such as PAM50 and Oncotype DX, do not segregate the Indian breast samples based on molecular subtypes. This study aims at finding signatures of long noncoding RNA (lncRNA) and mRNA in Indian breast cancer patients using RNA-seq. We have analyzed the survival based on the menopausal and hormone status of 380 Indian breast cancer patients, and of these, we have sequenced and analyzed matched tumor-normal transcriptome of 17 (pre- and postmenopausal) Indian breast cancer patients representing six different subtypes, namely, four patients in triple-positive, three patients in estrogen receptor-positive (ER+ve), three patients in estrogen and progesterone receptors-positive (ER+ve, PR+ve), two patients in human epidermal growth factor receptor (Her2+ve), three patients in triple-negative, and one patient in ER+ve and Her2+ve subtypes. We have identified a 25 mRNA-27 lncRNA gene set, which segregated the subtypes in our data. A pathway analysis of the differentially expressed genes revealed downregulated ECM interaction and upregulated immune regulation, cell cycle, DNA damage response and repair, and telomere elongation in premenopausal women. Postmenopausal women showed downregulated metabolism, innate immune system, upregulated translation, sumoylation, and AKT2 activation. A Kaplan-Meier survival analysis revealed that menopausal status, grade of the tumor, and hormonal status displayed statistically significant effects (p < 0.05) on the risk of mortality due to breast cancer. Her2+ve patients showed low overall survival. One of the unique lncRNA-mRNA pairs specific to the EP-subtype, SNHG12 and EPB41, showed interaction, which correlates with their expression level; SNHG12 is downregulated and EPB41 is upregulated in EP samples.

Health-related quality of life among breast cancer patients in India.

This study evaluated the health-related quality of life (HRQoL) among breast cancer patients during various phases of treatment and with different treatment modalities, which helps in monitoring treatment outcomes, assessing the well-being of patients, and conducting health technology assessments. A total of 534 interviews were conducted among the patients of breast cancer recruited at different stages of disease and with different treatment modalities. HRQoL was determined using EuroQoL five dimensions questionnaire with five levels (EQ-5D-5L), EuroQoL Visual Analogue Scale (EQ VAS), and the EORTC QLQ-BR23 instrument. The utility values were determined based on the Indian EQ-5D-5L value set. The socio-demographic and clinico-therapeutic determinants of HRQoL were evaluated using multiple linear regression. The mean utility value of breast cancer patients was 0.602 (SD = 0.311) and mean EQ VAS score was 75 (SD = 12.3). The mean utility value at diagnosis was 0.628, whereas utility value was 0.55, 0.595, and 0.64 for post-surgery, post-chemotherapy, and post-radiotherapy treatment groups, respectively. The most frequently reported problem was pain/discomfort (in 84.3% patients), followed by anxiety/depression (83.5%). On EORTC QLQ-BR23, the maximum symptom scale scores for systemic therapy side effects were reported in the post chemotherapy group. The body image score and future perspective score were better in patients undergoing breast conservative surgery (BCS) compared to patients undergoing modified radical mastectomy. Age, education, and employment status of the patient, type of treatment modality, and use of taxanes are the determinants of HRQoL in breast cancer patients. Clinical interventions should focus upon management of pain and anxiety. BCS should be offered to all eligible patients as it is associated with better HRQoL. Addressing the factors that independently affect the HRQoL will help in improving the treatment compliance and outcomes.

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.

Cancer Treatment-Induced Bone Loss: Role of Denosumab in Non-Metastatic Breast Cancer.

Chemotherapeutic agents, endocrine therapy and radiotherapy used in the management of breast cancer are known to cause decreased bone mineral density, and thus, increased incidence of fractures. A majority (~60%) of the breast cancer patients in India are either estrogen (ER) or progesterone hormone receptor (PR) positive. Adjuvant treatment with aromatase inhibitors (AIs) is the treatment mainstay for hormone-sensitive disease in postmenopausal (PM) women, with reduced bone mineral density (BMD), which results in increased fracture rates. Zoledronic acid, alendronate, risedronate and denosumab have been the agents of choice for managing bone loss. Denosumab 60 mg is approved for gaining bone mass in women with breast cancer who are at high risk for fracture following adjuvant AI treatment. The phase III HALT-BC data indicate an improvement in BMD with denosumab and a 50% reduction in clinical fractures, with significant improvements seen at the lumbar spine, distal third of the radius, and total hip. Denosumab has several advantages over other bone modifying agents such as subcutaneous self-administration by the patient themselves, no requirement of hospitalization, no dose modifications in renal impairment, and low incidence of acute phase anaphylactic reactions. We review the available evidence of denosumab for managing bone loss in non-metastatic breast cancer patients.

Abstract LB561: Germline mutational profiling of TNBCs in an Indian cohort

Abstract Breast cancer is the most common cancer in Indian women with a high incidence of triple negative breast cancer (TNBC), an aggressive subtype of breast cancer associated with poor prognosis. The high TNBC prevalence (&amp;gt;25%) in India as compared to the western population (10-15%) remains to be a challenge in clinical management. The association of germline BRCA1/2 mutations in TNBCs is well-established as a predisposing factor for hereditary breast cancer risk. However, these studies are predominantly from germline profiling of TNBCs representative of western population. Therefore, we aimed to investigate the germline profiles of breast cancer patients in India using a multi-institutional TNBC cohort based on ACMG consensus multi-gene NGS panel. Of 193 TNBC patients, we identified 57 pathogenic mutations (diagnostic yield = 29.53%) from various genes of which BRCA1 (41/57, 71.93%) and BRCA2 (8/57, 14.03%) were most commonly mutated. We observed a high prevalence of BRCA1 mutations (41/193, 21.24%) and BRCA2 mutations (8/193, 4.14%) in our cohort as compared to published literature. Additionally, 8 pathogenic mutations were also reported in non-BRCA cancer pre-disposing genes associated with the HR pathway like ATM, CHEK2, PALB2. 10 novel mutations were identified in 3 genes namely BRCA1, BRCA2 and PALB2. The most common type of mutations was found to be frame-shift which may cause protein truncation and loss of function. Furthermore, we identified 48 variants of unknown significance (24.9%) of which about 7% were in the BRCA1/2 genes. Data mining from global databases like TCGA, Genome Asia indicated that the novel mutations were unique to the Indian population compared to the germline profiles of different ethnicities. Our study confirms the major contribution of BRCA1/2 genes in TNBCs as reported in the literature. A high percentage of the women were found to be associated with young age onset which may be attributed to BRCA mutations. We have also assessed the association of clinicopathological parameters such as tumor grade, stage, recurrence to the germline mutational status. Our analysis shows significant association of germline mutational status with family history thus underlin the importance of multi-gene panel testing as recommended by NCCN guidelines. Moreover, our results also emphasize the need for designing/implementing guidelines specific to Indian population. In summary our results indicate that Indian TNBCs have a high prevalence of BRCA1/2 mutations. Large scale studies in future are warranted to validate these preliminary findings. Citation Format: Chaitanyanand Koppiker, Ashwini Bapat, Siddharth Gahlaut, Naveen Luke, Jisha John, Rupa Mishra, Aishwarya Konnur, Namrata Namewar, Ruhi Reddy, Shaheen Shaikh, Rituja Banale, Smeeta Nare, Laleh Busheri, Asha Reddy, Ashraf Mannan, Sabarinathan Radhakrishnan, Selvi Radhakrishna, Santosh Dixit. Germline mutational profiling of TNBCs in an Indian cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB561.

FOXO1 Gene Downregulation and Promoter Methylation Exhibits Significant Correlation With Clinical Parameters in Indian Breast Cancer Patients.

Background: Forkhead box “O” one which is member of Forkhead box family of transcription factors is known to play key role in different physiological processes including cell cycle arrest, autophagy, and apoptosis. FOXO1 is defined to play tumor suppressive role in various malignancies including breast cancer and its Dysregulation is frequently reported. However, the evaluation of FOXO1 promoter methylation and its expression at mRNA and protein level in different stages of breast cancer and its association with different clinical parameters is still not studied. Therefore, for better understanding the role of FOXO1 in breast cancer, in our study we examined the FOXO1 mRNA and protein expression in Breast cancer samples of Indian breast cancer patients. Results: Total 127 breast cancer samples along with adjacent normal tissue (n = 127) were analyzed through methylation specific PCR (MS-PCR), mRNA expression (Real-time PCR) and Immunohistochemistry (IHC). We detected 69.29% cases to be downregulated at the mRNA level, and 77.95% of cases exhibited no or low protein expression. In our data we report a significant association (p = 0.0001) between the downregulated protein expression and promoter hypermethylation of FOXO1 gene. We also found a significant correlation of FOXO1 mRNA level with Age (p = 0.008), age at first live birth (p = 0,003), tumor size (p = 0.05) and lymph node status (p = 0.01). Conclusion: we in our study report the tumor suppressive role of FOXO1 in case of Indian breast cancer patients and our data suggest it to exhibit prognostic importance. However, further research is needed to evaluate FOXO1 significance in diagnostic and therapeutic targeting in breast cancer cases.

Abstract P3-07-08: Germline mutational profiling in Indian TNBCs

Abstract Breast cancer is the most common cancer in Indian women with a high incidence of triple negative breast cancer (TNBC), an aggressive subtype of breast cancer associated with poor prognosis. The high TNBC prevalence (&amp;gt;25%) in India as compared to the western population (10-15%) remains to be a challenge in clinical management. The association of germline BRCA1/2 mutations in TNBCs is well-established as a predisposing factor for hereditary breast cancer risk. However, these studies are predominantly from germline profiling of TNBCs representative of western population. Therefore, we aimed to investigate the germline profiles of Indian breast cancer patients using a multi-institutional TNBC cohort based on ACMG consensus multi-gene NGS panel. In our study cohort of 193 TNBC patients, we identified 57 pathogenic mutations (diagnostic yield = 29.53%) from various genes of which BRCA1 (41/57, 71.93%) and BRCA2 (8/57, 14.03%) were most commonly mutated. We observed a high prevalence of BRCA1 mutations (41/193, 21.24%) and BRCA2 mutations (8/193, 4.14%) in our cohort as compared to published literature. Additionally, 8 pathogenic mutations were also reported in non-BRCA cancer pre-disposing genes associated with the HR pathway like ATM, CHEK2, PALB2. 10 novel mutations were identified in 3 genes namely BRCA1, BRCA2 and PALB2. The most common type of mutations was found to be frame-shift which may cause protein truncation and loss of function. Furthermore, we identified 48 variants of unknown significance (24.9%) of which about 7% were in the BRCA1/2 genes. Data mining from global databases like TCGA, Genome Asia indicated that the novel mutations were unique to the Indian population compared to the germline profiles of different ethnicities. Our study confirms the major contribution of BRCA1/2 genes in TNBCs as reported in the literature. A high percentage of the women were found to be associated with young age onset which may be attributed to BRCA mutations. Further analysis to investigate the association of tumor size, tumor grade, survival analysis with mutational profiles is in process. Similarly, we are also assessing. family history to underline the importance of multi-gene panel testing as recommended by NCCN guidelines. Moreover, our results also emphasize the need for designing/implementing guidelines specific to Indian population. In summary our results indicate that Indian TNBCs have a high prevalence of BRCA1/2 mutations. Large scale studies in future are warranted to validate these preliminary findings. Citation Format: C B Koppiker. Germline mutational profiling in Indian TNBCs [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 P3-07-08.