• Androgen receptor
• Androgens
• Antiandrogens
• Breast cancer
• Estrogen receptor
• Triple-negative breast cancer

• BI-RADS
• Breast cancer
• Cancer screening
• Early detection
• Mammography
• Mobile mammographic unit
• Public awareness
• Rural healthcare

• Humans
• Female
• Mammography/statistics & numerical data
• India/epidemiology
• Breast Neoplasms/diagnostic imaging
• Breast Neoplasms/diagnosis
• Retrospective Studies
• Middle Aged
• Early Detection of Cancer/statistics & numerical data
• Adult
• Mobile Health Units
• Aged
• Mass Screening/statistics & numerical data

• Breast cancer
• Breast-feeding
• Menarche
• Odds ratios
• Reproductive
• Women's menstrual

• Breast cancer
• Factors
• Screening
• Young Indian women

Breast cancer is the commonest malignancy among women globally. From being fourth in the list of most common cancers in India during the 1990s, it has now become the first. In this review, we examine the available literature to understand the factors that contributed to the high burden of breast cancer in the country. We also provide the landscape of changes in the field of early diagnosis and the treatment modalities as well as the limitations of the Indian healthcare delivery systems (e.g., delayed diagnosis, human resources and funding for treatment). This review also sheds light on the newer interventions and the future of breast cancer management keeping in mind the coronavirus disease 2019 imposed limitations.

• Breast cancer
• Challenges
• Prospects
• India
• Treatment

• BAP1
• BRCA1
• BRCA2
• breast
• cancer

Elucidation of specific and recurrent/founder pathogenic variants (PVs) in BRCA (BRCA1 and BRCA2) genes can make the genetic testing, for breast cancer (BC) and/or ovarian cancer (OC), affordable for developing nations.

To establish the knowledge about BRCA PVs and to determine the prevalence of the specific and recurrent/founder variants in BRCA genes in BC and/or OC women in North Africa, a systematic review was conducted in Morocco, Algeria, and Tunisia.

Search of the databases yielded 25 relevant references, including eleven studies in Morocco, five in Algeria, and nine in Tunisia. Overall, 15 studies investigated both BRCA1 and BRCA2 genes, four studies examined the entire coding region of the BRCA1 gene, and six studies in which the analysis was limited to a few BRCA1 and/or BRCA2 exons. Overall, 76 PVs (44 in BRCA1 and32 in BRCA2) were identified in 196 BC and/or OC patients (129 BRCA1 and 67 BRCA2 carriers). Eighteen of the 76 (23.7%) PVs [10/44 (22.7%) in BRCA1 and 8/32 (25%) in BRCA2] were reported for the first time and considered to be novel PVs. Among those identified as unlikely to be of North African origin, the BRCA1 c.68_69del and BRCA1 c.5266dupC Jewish founder alleles and PVs that have been reported as recurrent/founder variants in European populations (ex: BRCA1 c.181T>G, BRCA1 c1016dupA). The most well characterized PVs are four in BRCA1 gene [c.211dupA (14.7%), c.798_799detTT (14%), c.5266dup (8.5%), c.5309G>T (7.8%), c.3279delC (4.7%)] and one in BRCA2 [c.1310_1313detAAGA (38.9%)]. The c.211dupA and c.5309G>T PVs were identified as specific founder variants in Tunisia and Morocco, accounting for 35.2% (19/54) and 20.4% (10/49) of total established BRCA1 PVs, respectively. c.798_799delTT variant was identified in 14% (18/129) of all BRCA1 North African carriers, suggesting a founder allele. A broad spectrum of recurrent variants including BRCA1 3279delC, BRCA1 c.5266dup and BRCA2 c.1310_1313detAAGA was detected in 42 patients. BRCA1 founder variants explain around 36.4% (47/129) of BC and outnumber BRCA2 founder variants by a ratio of ≈3:1.

Testing BC and/or OC patients for the panel of specific and recurrent/founder PVs might be the most cost-effective molecular diagnosis strategy.

• BRCA genes
• North Africa
• Specific variant
• recurrent/founder variant

Breast cancer (BC) is the most common form of cancer among Asian females. Mutations in the BRCA1/BRCA2 genes are often observed in BC cases and largely increase the lifetime risk of having BC. Because of the paucity of high-quality data on the molecular spectrum of BRCA mutations in South Asian populations, we aimed to explore these mutations among South Asian countries.

A systematic literature search was performed for the BRCA1 and BRCA2 gene mutation spectrum using electronic databases such as PubMed, EMBASE, and Google Scholar. Twenty studies were selected based on specific inclusion and exclusion criteria.

The 185delAG (c.68_69del) mutation in exon 2 of BRCA1 was the most common recurrent mutation and founder mutation found. Various intronic variants, variants of unknown significance, large genomic rearrangements, and polymorphisms were also described in some studies.

The South Asian population has a wide variety of genetic mutations of BRCA1 and BRCA2 that differ according to countries and ethnicities. A stronger knowledge of various population-specific mutations in these cancer susceptibility genes can help provide efficient strategies for genetic testing.

• BRCA1
• BRCA2
• South Asia
• breast cancer
• mutation
• review

The occurrence rate of BRCA1 mutations is found to be high in South Asian countries where early onset of breast cancer is common. In Bangladesh, noticeable percentage of patients experience breast cancer in their reproductive ages. The objective of this study was to identify any mutation in exon2 of the BRCA1 gene in adult Bengali Bangladeshi female patients with breast cancer.

In this cross-sectional descriptive study, the genomic DNA was extracted from the blood of adult fifty Bengali Bangladeshi female breast cancer patients. The whole region of exon2 of the BRCA1 gene was amplified and the amplified DNA products were sequenced using Sanger sequencing. The raw chromatogram data were analyzed using Chromas software, and analyzed sequences were compared with the NCBI RefSeq database by BLAST search. The resultant amino acid change was detected by MEGA X software.

We found the mean age at diagnosis 44.66 years, whereas 96% of patients were married, 90% were multiparous and 86% breastfed their children. All patients had unilateral breast cancer and among them 94% had invasive ductal carcinoma. Only 24.5% of the patients had associated omorbidity. The family history of breast cancer or other BRCA-associated cancer was positive only for 4% of patients. A total of five mutations were identified all of which caused by substitutions. Among them three were nonsynonymous and two were synonymous. Only 2.5% of the patients, within the age group of 18-50 years, were found to have mutations in their blood, whereas 26.66% of the patients above 50 years found to have mutations in this study.

Among this small sample size, we found five mutations in exon2 of the BRCA1 gene and this indicates the necessity to find out the mutation spectra of the BRCA1 gene in the Bangladeshi population.

• breast cancer
• c.68-69delAG
• exon2 of BRCA1 gene
• nonsynonymous and synonymous mutation

• Breast cancer
• Disparity
• Genetic testing
• Precision medicine

Genetic changes in p53 gene contribute to breast cancer susceptibility.

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.

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.

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.

• Breast cancer
• Case-control
• Indian populations
• Meta-analysis
• p53 Arg72Pro polymorphism
• p53 codon72 SNP

• India
• PBCR
• breast
• cancer
• early age
• trends

• Breast cancer
• India
• human epidermal growth factor receptor 2-positive
• real world

Breast cancer is the most frequently occurring disease among women worldwide. The early stage of breast cancer identification is the key challenge in cancer control and prevention procedures. Although gene expression profiling helps to understand the molecular mechanism of diseases or disorder in the living system, gene expression pattern alone is not sufficient to predict the exact mechanisms. Current proteomics tools hold great application for analysis of cancerous conditions. Hence, the generation of differential protein expression profiles has been optimized for breast cancer and normal tissue samples in our organization. Normal and tumor tissues were collected from 20 people from a local hospital. Proteins from the diseased and normal tissues have been investigated by 2D gel electrophoresis and MALDI-TOF-MS. The peptide mass fingerprint data were fed into various public domains like Mascot, MS-Fit, and Pept-ident against Swiss-Prot protein database and the proteins of interest were identified. Some of the differentially expressed proteins identified were human annexin, glutathione S-transferase, vimentin, enolase-1, dihydrolipoamide dehydrogenase, glutamate dehydrogenase, Cyclin A1, hormone sensitive lipase, beta catenin, and so forth. Many types of proteins were identified as fundamental steps for developing molecular markers for diagnosis of human breast cancer as well as making a new proteomic database for future research.

• Amino Acid Sequence
• Apoptosis Regulatory Proteins
• Computational Biology
• Databases, Genetic
• Exons/genetics
• Humans
• Introns
• Membrane Proteins/genetics
• Molecular Sequence Data
• Polymerase Chain Reaction
• Protein Isoforms/genetics
• Sequence Alignment
• Sequence Analysis, Protein
• Software

• R01 GM085237 NIGMS NIH HHS
• R01 HL087017 NHLBI NIH HHS
• R03 HL095435 NHLBI NIH HHS
• R01GM085237 NIGMS NIH HHS

• BRCA1
• BRCA2
• Familial breast and/or ovarian cancer
• Inherited breast cancer

Recent reports suggest increase in estrogen receptor (ER), progesterone receptor (PR) negative breast cancer yet little is known about histology or receptor status of breast cancer in Indian/Pakistani women.in the U.S.

We examined the United States National Cancer Institute's Surveillance Epidemiology and End Results (SEER) Cancer program to assess: a) frequency of breast cancer by age, b) histologic subtypes, c) receptor status of breast cancer and, d) survival in Indians/Pakistanis compared to Caucasians. There were 360,933 breast cancer cases diagnosed 1988-2006. Chi-Square analyses and Cox proportional hazards models, to estimate relative risks for breast cancer mortality after adjusting for confounders, were performed using Statistical Analysis Software 9.2.

Among Asian Indian/Pakistani breast cancer patients, 16.2% were < 40 yrs. old compared to 6.23% in Caucasians (p < 0.0001). Asian Indian women had more invasive ductal carcinoma (69.1 vs. 65.7%, p < 0.0001), inflammatory cancer (1.4% vs. 0.8, p < 0.0001) and less invasive lobular carcinoma (4.2% vs. 8.1%, p < 0.0001) than Caucasians. Asian Indian/Pakistani women had more ER/PR negative breast cancer (30.6% vs. 21.8%, p = 0.0095) than Caucasians. Adjusting for stage at diagnosis, age, tumor grade, nodal status, and histology, Asian Indian/Pakistani women's survival was similar to Caucasians, while African Americans' was worse.

Asian Indian/Pakistani women have higher frequency of breast cancer (particularly in age < 40), ER/PR negative invasive ductal and inflammatory cancer than Caucasians.

In Asia, breast cancer is characterised by an early age of onset: In Malaysia, approximately 50% of cases occur in women under the age of 50 years. A proportion of these cases may be attributable, at least in part, to genetic components, but to date, the contribution of genetic components to breast cancer in many of Malaysia's ethnic groups has not been well-characterised.

Given that hereditary breast carcinoma is primarily due to germline mutations in one of two breast cancer susceptibility genes, BRCA1 and BRCA2, we have characterised the spectrum of BRCA mutations in a cohort of 37 individuals with early-onset disease (≤40 years) and no reported family history. Mutational analysis of BRCA1 and BRCA2 was conducted by full sequencing of all exons and intron-exon junctions.

Here, we report a total of 14 BRCA1 and 17 BRCA2 sequence alterations, of which eight are novel (3 BRCA1 and 5 BRCA2). One deleterious BRCA1 mutation and 2 deleterious BRCA2 mutations, all of which are novel mutations, were identified in 3 of 37 individuals. This represents a prevalence of 2.7% and 5.4% respectively, which is consistent with other studies in other Asian ethnic groups (4–9%).

• Alternative Splicing/genetics
• Computational Biology
• Gene Expression Regulation/genetics
• Regulatory Sequences, Nucleic Acid/genetics

• Adult
• Aged
• Breast Neoplasms/genetics
• Case-Control Studies
• DNA Mutational Analysis
• Female
• Frameshift Mutation
• Genes, BRCA2
• Genetic Predisposition to Disease
• Germ-Line Mutation
• Humans
• India/epidemiology
• Male
• Middle Aged
• Mutation, Missense
• Ovarian Neoplasms/genetics
• Prevalence

• Adult
• BRCA1 Protein/genetics
• Breast Neoplasms/genetics
• DNA Mutational Analysis
• Family Health
• Female
• Genetic Predisposition to Disease
• Germ-Line Mutation
• Humans
• India
• Male
• Ovarian Neoplasms/genetics
• Pedigree

• 070069 Wellcome Trust

A large number of distinct mutations in the BRCA1 and BRCA2 genes have been reported worldwide, but little is known regarding the role of these inherited susceptibility genes in breast cancer risk among Indian women. We investigated the distribution and the nature of BRCA1 and BRCA2 germline mutations and polymorphisms in a cohort of 204 Indian breast cancer patients and 140 age-matched controls.

Cases were selected with regard to early onset disease (≤40 years) and family history of breast and ovarian cancer. Two hundred four breast cancer cases along with 140 age-matched controls were analyzed for mutations. All coding regions and exon-intron boundaries of the BRCA1 and BRCA2 genes were screened by heteroduplex analysis followed by direct sequencing of detected variants.

In total, 18 genetic alterations were identified. Three deleterious frame-shift mutations (185delAG in exon 2; 4184del4 and 3596del4 in exon 11) were identified in BRCA1, along with one missense mutation (K1667R), one 5'UTR alteration (22C>G), three intronic variants (IVS10-12delG, IVS13+2T>C, IVS7+38T>C) and one silent substitution (5154C>T). Similarly three pathogenic protein-truncating mutations (6376insAA in exon 11, 8576insC in exon19, and 9999delA in exon 27) along with one missense mutation (A2951T), four intronic alterations (IVS2+90T>A, IVS7+75A>T, IVS8+56C>T, IVS25+58insG) and one silent substitution (1593A>G) were identified in BRCA2. Four previously reported polymorphisms (K1183R, S1613G, and M1652I in BRCA1, and 7470A>G in BRCA2) were detected in both controls and breast cancer patients. Rare BRCA1/2 sequence alterations were observed in 15 out of 105 (14.2%) early-onset cases without family history and 11.7% (4/34) breast cancer cases with family history. Of these, six were pathogenic protein truncating mutations. In addition, several variants of uncertain clinical significance were identified. Among these are two missense variants, one alteration of a consensus splice donor sequence, and a variant that potentially disrupts translational initiation.

BRCA1 and BRCA2 mutations appear to account for a lower proportion of breast cancer patients at increased risk of harboring such mutations in Northern India (6/204, 2.9%) than has been reported in other populations. However, given the limited extent of reported family history among these patients, the observed mutation frequency is not dissimilar from that reported in other cohorts of early onset breast cancer patients. Several of the identified mutations are unique and novel to Indian patients.

• Adolescent
• Adult
• Aged
• Breast Neoplasms/epidemiology
• Breast Neoplasms/genetics
• Breast Neoplasms, Male/epidemiology
• Breast Neoplasms, Male/genetics
• Case-Control Studies
• Female
• Frameshift Mutation
• Genes, BRCA1
• Genes, BRCA2
• Germ-Line Mutation
• Humans
• India/epidemiology
• Male
• Middle Aged
• Mutation, Missense

• Adult
• Aged
• Base Sequence
• Breast Neoplasms/epidemiology
• Breast Neoplasms/genetics
• DNA Mutational Analysis
• Female
• Genes, BRCA1
• Genes, p53
• Genetic Predisposition to Disease
• Humans
• India
• Middle Aged
• Mutation
• Polymerase Chain Reaction
• Polymorphism, Single-Stranded Conformational
• Risk Factors

• Adult
• Aged
• Breast Neoplasms/genetics
• Case-Control Studies
• DNA Mutational Analysis
• Female
• Genes, BRCA1
• Genes, BRCA2
• Genes, p53
• Genetic Predisposition to Disease
• Germ-Line Mutation
• Humans
• India/epidemiology
• Middle Aged
• Pedigree
• Prevalence