Breast Cancer In Indian Population Research Articles

Assessment of serum microRNA-21 and miRNA-205 as diagnostic markers for stage I and II breast cancer in Indian population

Assessment of serum microRNA-21 and miRNA-205 as diagnostic markers for stage I and II breast cancer in Indian population

23P Vitamin D deficiency and SNPs in melatonin pathway genes potentiate breast cancer susceptibility: A pilot study

Previous studies have documented that both vitamin D deficiency and single nucleotide polymorphism (SNPs) of genes responsible for mediating downstream effects of melatonin with development of breast cancer. In India 70 percent of the population suffers from Vitamin D deficiency. There are no available reports on association of vitamin D and SNPs in Melatonin genes towards development of breast cancer in Indian population.

Genomic approach to identify association of environmental bisphenol-A (BPA) in daily use plastics as molecular disruptors in breast cancer

PurposeThe present study was aimed to investigate the association of Bisphenol-A (BPA) and MDM2 SNP309 polymorphism with the risk of breast cancer in Indian women. MethodsBlood samples from breast cancer patients and healthy controls were analyzed by using UV visible spectrophotometry for structural changes in blood components by BPAQ. MDM2 SNP309 polymorphism was investigated by using TETRA ARMS-PCR. ResultsOn comparing control groups, there is an increased mean absorbance at a range of 250 nm to 300 nm and 360 nm to 450 nm in breast cancer patients. The allele frequencies of case subjects (T, 0.47; G, 0.53) were significantly different from those of control subjects (T, 0.66; G, 0.34) (p = 0.011). The proportion of GG genotype of the SNP309 in breast cancer patients (28.88%) was significantly higher than that of control groups (13.33%). With TT genotype as reference, the genotypes (TG + GG) containing G allele as dominant form in breast cancer patients (OR, 2.80; 95% CI, 1.12–7.00); p = 0.025) were significantly associated with breast cancer. ConclusionsThe results revealed that there is an association between active metabolite of Bisphenol-A and MDM2 SNP309 G variant with the risk of breast cancer in Indian population.

Multicentric real world evidence with palbociclib in hormone positive HER2 negative metastatic breast cancer in Indian population

The combination of cyclin dependent kinase 4/6 inhibitors with endocrine therapy is the standard therapy in hormone receptor positive HER-2 negative metastatic breast cancer (HR+/HER2− MBC). Several randomized trials have shown the benefits of this combination, however, real world evidence in the Indian patients is warranted. The present study reports the largest real world multicentric data from Indian population on the use of Palbociclib in HR+/HER2− MBC. A multicentric study on the HR+/HER2− MBC patients who received palbociclib with hormonal agent (Aromatase inhibitors/Fulvestrant) between February 2017 and May 2020 was conducted. Clinical and demographic information and survival data was retrieved from the Hospital medical records. Among a total of 188 patients, 57% patients were premenopausal and 17% patients had bone only disease. Altogether, 115 (61%) patients received palbociclib with Aromatase inhibitors in the first line whereas 73 (39%) patients received it in the second line with Fulvestrant. The median follow up period with advanced disease was 13 months. The median progression free survival in the first line and second line was 20.2 months and 12 months, respectively (p-value < 0.0001). The objective response rate was 80% and 47.9% in first and second lines, respectively. Dose interruptions/ discontinuation were done in 14.9% and 2.7% patients in the first and second lines, respectively. In terms of toxicity, 10% patients had grade 3–4 adverse events. The present real world data of the use of palbociclib in Indian population suggests similar effectiveness to previously published real world evidences and has been adapted as the standard of care in the first and second line treatment of HR+/HER2− MBC.

Prevalence of Molecular Subtypes in Operated Cases of Breast Cancer and Its Clinicopathological Correlation: A Single Institute Study from a Tertiary Cancer Centre in North India.

Breast cancer has emerged as a major health problem among women in India. There are few Indian studies which have looked at prevalence of molecular subtypesof breast cancer in Indian population. The primary objective of our study was to find out the prevalence of various molecular subtypes in operated cases of breast cancer patients presenting to us. Three hundred sixty patients who were operated in our department were analysed. Clinicopathological features of all cases were recorded. Classification into various molecular subtypes was done using St. Gallen 2013 criteria. Luminal B HER2 negative was the predominant molecular subtype in our study population constituting 30.3% of patients. The percentage of aggressive subtypes, viz. triple negative breast cancer and HER2 enriched, were 21.7% and 11.4% respectively. Only 19.4% of patients in our study population had tumour size ≤ 2cm with nodes being positive in 56.9% of our patients at presentation. Data from our study and other studies published from India show that the two most aggressive subtypes of, viz. triple negative breast cancer and HER2 enriched, may be more prevalentin our population as compared to western population.

BCL-2 (-938C>A), BAX (-248G>A), and HER2 Ile655Val Polymorphisms and Breast Cancer Risk in Indian Population.

Breast cancer is the most common carcinoma in women worldwide. The present case-control study was aimed to examine the association of BCL-2 (-938C> A), BAX (-248G > A), and HER2 (I655V i.e. A > G) polymorphisms with breast cancer risk in Indian population. This study enrolled 117 breast cancer cases and 104 controls. BCL-2 (-938C > A), BAX (-248G > A), and HER2 Ile655Val polymorphisms were screened by PCR-RFLP method. There was no significance difference in the allelic and genotype frequency of the BCL-2 (-938C > A) and BAX (-248G > A) polymorphisms between cases and controls. In relation to HER2 Ile655Val polymorphism, the statistical analysis of observed genotypic frequencies showed significant association (p-0.0059). Compared to Ile/Ile (A/A) genotype, frequency of Ile/Val (A/G) genotype was significantly higher among cases than in control group and observed to increase the breast cancer risk (OR, 2.43; 95%CI, 1.32–4.46; p-0.004). The frequency of Val (G) allele was significantly higher in cases as compared to controls (6.83% vs 2.88%, resp.). Compared to Ile (A) allele, significant increase in the risk of breast cancer was observed with Val (G) allele (OR, 2.21; 95% CI, 1.35–3.63; p-0.0016). We observed significant association between HER2 Ile655Val polymorphism and breast cancer risk under the dominant (OR = 2.52; 95% CI: 1.41–4.51; p-0.001) and codominant (OR, 2.24; 95% CI: 1.23–4.09; p-0.008) model. In our study, BCL-2 (-938C > A) and BAX (-248G > A) polymorphism were not found to be associated with breast cancer risk. This present study for the first time shows significant association of HER2 Ile655Val polymorphism with risk of breast cancer in Indian population. Therefore, we suggest that each population need to evaluate its own genetic profile for breast cancer risk that may be helpful for better understanding the racial and geographic differences reported for breast cancer incidence and mortality.

ANKLE1 as New Hotspot Mutation for Breast Cancer in Indian Population and Has a Role in DNA Damage and Repair in Mammalian Cells.

Breast cancer has replaced cervical cancer as being the most common and having the highest mortality among women in India. ANKLE gene is conserved among organisms during evolutionary succession and is a member of LEM family proteins in lower metazoans and is involved in critical functions in the nuclear architecture, gene expression and cell signaling. ANKLE1 is the human orthologous of LEM-3 and is involved in DNA damage response and DNA repair. Whole Exome Sequencing (WES) of paired breast cancer samples was performed and ANKLE1 was found to be a new possible hotspot for predisposition of breast cancer. The mass array genotyping for breast cancer variant rs2363956 further confirmed the ANKLE1 association with the studied population of breast cancer. To elucidate the role of ANKLE1 in DNA damage, it was knocked down in MCF-7 breast cancer cell line and the expression of γH2AX was assessed. ANKLE1 knockdown cells displayed elevated levels of γ-H2AX foci in response to the cisplatin induced replication stress. The localization pattern of ANKLE1 further emphasized the role of ANKLE1 in DNA repair process. We observed that ANKLE1 is required for maintaining genomic stability and plays a role in DNA damage and repair process. These findings provided a molecular basis for the suspected role of ANKLE1 in human breast cancer and suggested an important role of this gene in controlling breast cancer development among women in India.

Male Breast Cancer: Current Trends-a Tertiary Care Centre Experience.

Male breast cancer is a rare tumour in all parts of the world. About 1% of all breast cancers occur in men. Occurrence of male breast cancer peaks at age 71years. Familial cases usually have BRCA2 rather than BRCA1 mutations. Presentation is usually a lump or nipple inversion, but is often late, with more than 40% of individuals having stage III or IV disease. We retrospectively reviewed 25 male patients with breast cancer who came to the HCG Cancer Centre, Ahmedabad between 2014 and 2018, and their demographic details, tumor profile, and radiological, histopathological as well as luminal profile findings were studied. The average age at presentation and detection of male breast cancer was 61.08years. Incidence of male ca. breast over these 4years was 4.75/year which had a significant increase compared with our own data in the last 8years (3/year). Male to female ratio for ca. breast was 1:61. One out of 25 (4%) patients had gynaecomastia. The most common histology was invasive ductal carcinoma-not otherwise specified with none of the patients having lobular carcinoma. Majority of patients were ER/PR positive and HER-2 negative. Male breast cancer is having a rising incidence, which in our study is 1.56%. Males have relatively older age at presentation and stage-by-stage treatment remains the same. Males are more likely to be having prognostically favourable luminal subtypes. Male breast cancer in Indian population is currently experiencing an increasing trend. Improved awareness amongst patients and high index of suspicion by the clinicians along with accurate diagnostic techniques help detect the disease at an earlier stage culminating into prolonged overall and disease-free survival.

A prospective study of wound complications in cancer breast surgery following neoadjuvant chemotherapy

Background: Neoadjuvant chemotherapy is most of the time suitable for subset of the patients of breast cancer in Indian population. Neoadjuvant chemotherapy may be used to down stage a tumor that is inoperable in its current state, so that curative resection becomes feasible. But also, it can decrease size of operable primary tumour so that breast conserving surgery become possible which has better functional outcome and improves the quality of life. Therefore, there is a need to improve understanding of potential for post-operative complications in recipients of Neoadjuvant chemotherapy. Given that neutropenia is most common side effect of chemotherapeutics, this has raised concerns regarding the increased risk of post-operative complications. The objective of present study is to examine the risk of post-operative wound complications in patients receiving neoadjuvant chemotherapy for breast cancer.Methods: This study was conducted on 60 patients of breast carcinoma admitted for treatment to Nehru Hospital, BRDMC Gorakhpur for treatment during the period of July 2016-December 2017.Results: Seroma formation was most common complication observed in 20% (12/60) patients followed by superficial surgical site infection in 6.67% (4/60) patients, Deep surgical site infection in 2 patients (3.33%). Wound dehiscence in 2 (3.33%) patients. These data suggested that no obvious increase in complications in patients gone for neoadjuvant chemotherapy.Conclusions: Authors concluded that the rate of wound complications for breast cancer patients receiving Neoadjuvant chemotherapy is low. Seroma formation is the most frequent complication. Other complications can be avoided if proper preventive measures are taken. Smoking, hypertension, DM and obesity were associated with an increased risk of wound complications for patients undergoing BCS or MRM.

Impact of p53 arg72pro SNP on Breast Cancer Risk in North Indian Population.

Background: Genetic changes in p53 gene contribute to breast cancer susceptibility.Objective and Methods: A case-control study and a meta-analysis were performed to investigate the role of p53 codon72 SNP with breast cancer susceptibility in Indian women.Results: p53 heterozygous arginine variant was associated with decreased risk of breast cancer in total cohort. In meta-analysis, Allelic and GG vs. CC genetic comparison model were found to be associated with breast cancer risk. Moreover, recessive comparison model indicated a protective correlation with breast cancer occurrence.Conclusion: The findings of our case-control study and meta-analysis suggest a significant association between p53 Arg72Pro polymorphism and an increased risk of breast cancer in Indian population.

Risk factors associated with carcinoma breast: a case control study

Background: The burden of breast cancer is increasing in both developed and developing countries; the peak occurrence of breast cancer in developed countries is above the age of 50 whereas in India it is above the age of 40. Reproductive factors contribute most to the development of breast cancer. Nulliparity, more age at first live birth and no breastfeeding are major reproductive risk factors for breast cancer in the developed countries. The role of reproductive factors in the development of breast cancer in Indian population is different as compared with that seen in the western population. Objective of this study was to find out some of the various risk factors of breast cancer among patients attending the tertiary care hospital in Hassan.Methods: The case control study was conducted at surgery wards of Sri Chamarajendra district hospital which is a teaching hospital. The calculated number of cases was 110, including 110 controls total 220 individuals were included in the study. A case was defined as any female patient histopathologically confirmed to have breast cancer.Results: The maximum cases (38%) were between 51 to 60 years of age group. Age at menarche, age at first child birth, age at marriage and age at menopause reported significant risk for breast cancer.Conclusions: Information, education and communication activities regarding these risk factors, early signs and symptoms of breast carcinoma, and breast self‑examination should be imparted to the women to create awareness about this fatal disease.

Triple negative breast cancer in Indian population: An analysis from a tertiary cancer center in India

Triple negative breast cancer in Indian population: An analysis from a tertiary cancer center in India

Variation in Copy Number of MTUS1 Gene among Healthy Individuals and Cancer Patients from Gujarat

Genome variations in the form of single nucleotide polymorphism, INDELs (insertions or deletions) and, duplications, inversions and copy number variations are more widely prevalent than initially predicted. Mitochondrial tumor suppressor gene maps on chromosome 8p, in which exon 4-specific deletion is associated with susceptibility towards breast and various other forms of cancer. In this study, 41 head and neck cancer, 15 breast cancer patients and 280 healthy control individuals were analyzed for mitochondrial tumor suppressor gene copy number variation. The frequencies of wt/wt (homozygous wild-type), wt/Del (heterozygous variant) and Del/Del (homozygous deletion variant) mitochondrial tumor suppressor gene genotypes were found to be 73.3%, 26.7%, and 0% in breast cancer patients, 41.5%, 58.5%, and 0% in head and neck cancer patients and 43%, 57%, and 0% in healthy individuals, respectively. A significant association of the deletion variant with breast cancer (odds ratio = 0.27, 95% confidence interval = 0.08–0.87, P = 0.0207) was found in our population. In addition, the allele and genotype frequency varied significantly (P<0.0001) among Indian and German populations, reflecting ethnic diversity. This pilot case-control study highlighted the indicative role of mitochondrial tumor suppressor gene deletion in protection from breast cancer in Indian population. However, the findings need to be investigated in larger patient sample size before any conclusive role of mitochondrial tumor suppressor gene copy number variation on cancer risk.

Abstract 2795: Replicating GWAS SNPs for breast cancer in Indian population

Abstract Background: There have been large Genome Wide Association Studies (GWAS) on breast cancer in most developed countries showing low to modest associations between common polymorphisms and breast cancer risk. In India, however, there have been no GWAS studies and few properly designed retrospective studies with smaller sample size on genetic susceptibility to study this risk. Methodology: DNA was extracted from buffy coat samples in 1204 cases and 1212 control. A customized panel of 384 SNPs was designed using a mixture of 3 strategies such as SNPs selected from GWAS, SNPs selected from Candidate Studies and SNPs selected using Bioinformatics tool. Genotyping was performed on the Illumina Hi-Scan using GoldenGate Genotyping (GGGT) Custom SNP Panel assay on all DNA samples extracted. The reproducibility rate of all the replicate samples (n = 160) for all the assays was 99% and above. Unconditional logistic regression (additive model) was used to estimate OR and corresponding 95% CI between genotypes and case status. This abstract focuses on replicating SNPs in Indian population which have shown to be associated in already conducted GWAS mostly in developed nations. Results: Seven SNPs were replicated from previous studies on BC GWAS. Prevalence of certain SNPs in the present study varied with that observed in GWAS. Out of 40 SNPs which did not show an association with BC, 15 SNPs had a MAF below 20% and 25 SNPs had prevalence of 20% and above. The risk of SNPs which were significantly identified in BC GWAS and in present study were also studied in BCs stratified on hormone receptor status. The SNP rs2046210 in ESR1 showed an increased risk for BCs which were ER-/PR- and triple negative but not ER+/PR+. The SNPs rs10411161 in Zinc Finger Protein 577 (ZNF577) gene showed significant protection in the development of only ER+/PR+ BCs whereas SNPs in FGFR2 (rs2981575, rs2981582), Mitogen-Activated Kinase Kinase Kinase 1 (MAP3K1) (rs889312) and 9q31.2 (rs865686) increased the risk of hormone receptor positive BC. Discussion: SNPs selected from FGFR2 gene were positively associated with BC. 25 SNPs which were identified as a risk factor for BC in the GWAS conducted in other populations did not replicate in the Indian population, even though their prevalence was high (≥ 20%) indicating that they may not be a risk factor in Indian population. The 3 SNPs which were highly prevalent in GWAS population could not be replicated even if they were associated the attributable risk of the SNPs remains low due to their low prevalence in the present study population. The SNPs associated with ER+/PR+ and ER-/PR- BCs were observed to be different suggesting that the cancer stratified on hormone receptor status may differ due to different biological pathways. Citation Format: Rajini T. Nagrani, Sharayu Sitaram Mhatre, Rajendra Badwe, Rajesh Dikshit. Replicating GWAS SNPs for breast cancer in Indian population. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2795. doi:10.1158/1538-7445.AM2015-2795

A Comparison of Clinical Features, Pathology and Outcomes in Various Subtypes of Breast Cancer in Indian Women.

Breast cancer is often classified into subtypes using immunohistochemical markers. These subtypes have distinct biological behaviour. This study was conducted with the aim of estimating the distribution of various subtypes of breast cancer in Indian population based on immunohistochemistry markers and to determine the clinical features, pathology and outcomes of these subtypes of breast cancer. A retrospective study was undertaken and all patients of breast cancer over a 5 year period were included. These patients were divided into 4 subgroups depending on the presence or absence of immunohistochemical markers: i) Luminal A (ER/PR+, Her 2 neu-); ii) Luminal B (ER/PR+, Her 2 neu+); iii) Her 2 enriched (ER-/PR-, Her 2 neu+) and; iv) Triple negative (ER-, PR-, Her2 neu-). Clinical and pathological features and survival were compared between patients in the 4 subgroups. Luminal A subgroup had majority of patients (43.8%). Patients in Luminal B, Her 2 enriched, and Triple negative subgroups were 14.8%, 16.1% and 25.3%. Median follow-up of patients was for 34 months. Luminal A subgroup patients were more likely to be postmenopausal and have smaller and lower grade (I/II) tumours with better survival (OS-91.06%). Patients in the Triple negative subgroup were more likely to be premenopausal (p-value 0.036, odds ratio 0.611, CI 0.394-0.949), have larger and higher grade (III) tumours with worse overall survival (OS-88.46%, odds ratio 1.32, 95%CI 0.602-2.39). Her 2 enriched group patients had bad prognostic features like larger size of tumour and higher grade of tumour and worst survival among all the subgroups (OS-85.07%, odds ratio 1.78, 95% CI 0.767-4.163). However, these outcomes were not statistically significant for the subgroups. A retrospective study was undertaken of breast cancer patients in India, according to subtypes based on immunohistochemistry. Luminal A had prognostic features and survival which was better as compared to other subgroups (Luminal B, Her 2 enriched and Triple negative). Incidence of patients with Triple negative breast cancer was higher in the premenopausal period. Patients with Her 2 enriched breast cancer had the worst survival among all the subgroups.

Hormone Related Risk Factors and Breast Cancer: Hospital Based Case Control Study from India

Breast cancer is the second most common malignancy in Indian women. Basically it is a hormone mediated disorder due to continuous exposure to ovarian hormones. Several established modifiable and non modifiable risk factors influence hormonal status which is associated with breast cancer. Prevalence and profile of risk factors of breast cancer differs region wise. Although etiology of breast cancer is complex and multifactorial involving genetic, hormonaland environmental factors, various studies showed significant role of reproductive risk factors in breast tumor genesis. Present study was aimed to explore association of various hormone related risk factors with breast cancer in Indian women. This hospital based case control study included newly diagnosed cases of breast cancer and age matched healthy women as controls. Standard structured pretested valid questionnaire was administered to record socio demographic data, medical, family, past history, use of hormones and reproductive risk factors. Participants were asked about marital status, number of live births, abortions, age at first live birth and breastfeeding duration history. Information was also obtained regarding age at menarche, menopausal status, age at menopause and use of oral contraceptives and hormone replacement therapy. Anthropometric measures body mass index and waist: hip ratio were taken as index of adiposity. We found significant association (p＜ 0.05) of age, menopausal status, use of oral contraceptives and postmenopausal obesity with breast cancer in comparison with controls. Present study has provided possible association of hormone related risk factors in breast cancer in Indian population.