Pakistani Breast Cancer Patients Research Articles

Advancing Immediate Breast Reconstruction Surgery in Pakistan: Bridging Literature Gaps and Meeting Patient Needs

Breast cancer ranks as the most diagnosed cancer globally and the leading cause of cancer mortality in women, with Pakistan exhibiting a particularly high incidence. However, breast reconstruction surgery, a critical intervention post-mastectomy, remains underutilized in Pakistan due to various barriers. Recent studies shed light on patient perspectives and outcomes regarding immediate breast reconstruction (IBR), indicating its positive impact on psychosocial well-being. Despite these insights, significant literature gaps persist, including the need for comprehensive national data, addressing cultural and awareness barriers, improving access and education, and prioritizing patient-centered care. This short communication underscores the urgency of addressing these gaps to advance breast reconstruction surgery in Pakistan. By conducting comprehensive studies, tackling cultural barriers, and prioritizing patient-centered care, we can ensure improved care and quality of life for Pakistani breast cancer patients. This call to action aims to transform the landscape of breast reconstruction surgery in Pakistan, offering hope for a brighter future for patients.

The Prevalence of BRCA1 and BRCA2 Mutations in Breast Cancer Patients

Aim: Genetic mutations in BRCA1 and BRCA2 are crucial for breast cancer risk assessment and treatment planning. Methods: This prospective observational study at Jinnah Postgraduate Medical Centre, Pakistan, involved female breast cancer patients aged 18 or older. The sample size calculation was based on a 3.4% prevalence rate of BRCA mutations, aiming for a 95% confidence level. Data on demographic, clinical characteristics, and genetic testing for BRCA mutations were collected and analyzed using SPSS version 23. Results: Among the study participants, 10% exhibited BRCA1 or BRCA2 mutations. The majority were diagnosed at stage 3 tumor development, with invasive ductal carcinoma being the predominant histological type. No significant familial predisposition to breast cancer was noted among the majority. Educational status and ethnicity showed varying associations with BRCA mutation presence. Conclusion: The study highlights a modest incidence of BRCA mutations among Pakistani breast cancer patients, underscoring the importance of genetic testing for risk assessment and targeted treatment. The findings support the need for comprehensive genetic screening programs in Pakistan, considering the diverse demographic and clinical characteristics of the population. Keywords: BRCA mutations, breast cancer, genetic testing, Pakistan, risk assessment, targeted treatment.

MicroRNAs hsa-miR-222-3p, hsa-let-7b-5p, and hsa-let-7f-5p Regulate Their Putative Target Genes HMGA1 and CDKN1B in Pakistani Breast Cancer Patients

MicroRNAs hsa-miR-222-3p, hsa-let-7b-5p, and hsa-let-7f-5p Regulate Their Putative Target Genes HMGA1 and CDKN1B in Pakistani Breast Cancer Patients

CYP2C19*17 association with higher plasma 4-hydroxy tamoxifen in Pakistani (estrogen-positive) breast cancer patients.

Breast cancer (BC) continues to be the most common cancer in the women worldwide. Since estrogen receptor (ER)-positive BC accounts for the majority of newly diagnosed cases, endocrine therapy is advised to utilize either tamoxifen (Tam) or aromatase inhibitors. The use of Tam as a monotherapy or in conjunction with an aromatase inhibitor following two or three years of endocrine therapy has long been recommended. When used adjuvantly, Tam medication reduces BC mortality and relapses, while it extends survival times in metastatic BC when used in conjunction with other treatments. Unfortunately, the efficiency of Tam varies considerably. This study was conducted to explore the influence of genetic polymorphisms in CYP2C19 gene on Tam's pharmacogenetics and pharmacokinetics in estrogen-positive BC patients. Data from healthy, unrelated individuals (n = 410; control group) and ER-positive BC patients (n = 430) receiving 20 mg of Tam per day were recruited. Steady-state plasma concentrations of Tam and its three metabolites were quantified using the high-performance liquid chromatography in the patients. The CYP2C19 polymorphisms were genotyped using an Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR) approach. More than 65% of healthy individuals were extensive metabolizers (*1/*1) for CYP2C19, whereas more than 70% of ER-positive BC patients were rapid and ultrarapid metabolizers (*1/17*, *17/17*). The polymorphism CYP2C19*17 is significantly associated with higher 4-hydroxytamoxifen (4-OH-Tam). Patients with the *17/*17 genotype exhibited 1- to 1.5-fold higher 4-OH-Tam, which was also high in patients with the *1/*2 and *2/*2 genotypes.

Contribution of constitutional BRCA1 promoter methylation to early-onset and familial breast cancer patients from Pakistan.

Constitutional BRCA1 promoter methylation has been identified as a potential risk factor for breast cancer (BC) in the Caucasian population. However, this data is lacking for BC patients of Asian origin. Therefore, we assessed the contribution of constitutional BRCA1 promoter methylation in Pakistani BC patients. A total of 385 BRCA1/2-negative index BC patients (197 early-onset BC (≤ 30years), 152 familial BC, 17 familial BC and ovarian cancer, 19 male BC) and 107 healthy controls were screened for the constitutional BRCA1 promoter methylation by methylation-sensitive high-resolution melting assay. Overall, 131 patients displayed triple-negative BC (TNBC) and 254 non-TNBC phenotypes. The prevalence of BRCA1 promoter methylation was calculated based on clinicopathological characteristics using univariable and multivariable logistic regression models. Constitutional BRCA1 promoter methylation was identified in 19.5% (75/385) of BC patients and 13.1% (14/107) of controls. The frequency of methylation was higher in early-onset BC (23.4% vs. 13.1%, P = 0.035) and TNBC patients (29.0% vs. 13.1%, P = 0.004) compared to controls. Methylation was also more prevalent in patients with high-grade than low-grade tumors (21.7% vs. 12.2%, P = 0.034) and progesterone receptor (PR)-negative than PR-positive tumors (26.0% vs. 13.9%, P = 0.004). Constitutional BRCA1 promoter methylation remained independently associated with TNBC phenotype (odds ratio 1.99; 95% CI 1.12-3.54; P = 0.02) after adjusting for BC diagnosis age, tumor grade, ER, and PR status. Constitutional BRCA1 promoter methylation is associated with TNBC and can serve as a non-invasive blood-based biomarker for Pakistani TNBC patients.

69P Chasing the origin of 23 recurrent BRCA1 mutations in Pakistani breast and ovarian cancer patients

Knowledge of population specific BRCA1/2 founder mutations provides a valuable and cost-effective genetic testing strategy. Twenty-three recurrent BRCA1 mutations have been identified previously in 100 Pakistani breast and/or ovarian cancer families. These accounted for 72.5% of all BRCA1 mutations identified. In this study, we investigated whether these mutations (identified in >2 unrelated patients) have a common ancestral origin and estimated the ages of these mutations. Haplotype analyses were performed in 188 individuals (100 index patients, 88 relatives) from Pakistani breast/ovarian cancer families, all harboring one of the 23 recurrent BRCA1 mutations, and 90 healthy controls. Six microsatellite markers (D17S800, D17S1801, D17S855, D17S1322, D17S1323, and D17S951) were analyzed. Mutation ages were estimated using DMLE+2.3 software. An identical haplotype of different length was found in families harboring the same BRCA1 mutation and suggested founder effects for all 23 mutations. Sixteen founder mutations were ethnicity-specific: 15 occurred in families of Punjabi background and one in a family of Pathan background. The remaining seven mutations occurred in families with two ethnic backgrounds. All BRCA1 founder mutations were estimated to have arisen approximately 147 to 159 generations ago. Our findings suggest founder effects for all 23 recurrent BRCA1 mutations. Our findings suggest founder effects for all 23 recurrent BRCA1 mutations. This knowledge allows the design and development of a cost effective local genetic testing strategy in Pakistan.

Cytochrome CYP2B6 Gene Polymorphism and Urinary Adverse Effects in Pakistani Breast Cancer Patients taking Cyclophosphamide

Cytochrome CYP2B6 Gene Polymorphism and Urinary Adverse Effects in Pakistani Breast Cancer Patients taking Cyclophosphamide

Editor's Summaries of the Articles Published in This Issue of Precision Medicine Communications

Editor's Summaries of the Articles Published in This Issue of Precision Medicine Communications

Breast Cancer Among Different Ethnicities (A Single Institution Study)

Objective: To study the socio-demographic factors, medical history, histological type, hormonal status with the different ethnic groups of Pakistani breast cancer patients.
 Study Design: Cross-sectional analytical study.
 Place and Duration of Study: Medical Oncology Department of Jinnah Postgraduate Medical Centre, Karachi Pakistan, from Aug -Nov 2019.
 Methodology: Two hundred female patients aged 20-50 years with histopathologically confirmed breast cancer visited OPD for the treatment or were admitted to the ward. The information regarding socio-demographics was noted in the pre-designed proforma. Divisions such as Muhajir (Urdu speaking), Sindhi, Balochi, Punjabi and Pathan were created to analyse breast cancer frequency within different ethnic classes in Pakistan. SPSS version 23 was used to analyse the data.
 Results: Out of 200 patients with breast carcinoma, 94 females were Urdu speaking (47%), 39 were Sindhi (19%), 25 were Punjabi (12%), 13 were Pathan (7%), seven were Baloch (4%), and 22 (11%) belonged to minority ethnic groups. The results showed a significant association of ethnicity with family history (p=0.053), residence (p=0.001) and employment status (p=0.010).
 Conclusion: The results of this study demonstrated that there is difference in breast cancer occurrence among ethnic groups.

Chasing the origin of 23 recurrent BRCA1 mutations in Pakistani breast and ovarian cancer patients.

Knowledge of population specific BRCA1/2 founder mutations provides a valuable and cost-effective genetic testing strategy. Twenty-three recurrent BRCA1 mutations have been identified previously in 100 Pakistani breast and/or ovarian cancer families. These accounted for 72.5% of all BRCA1 mutations identified. In our study, we investigated whether these mutations (identified in ≥2 unrelated patients) have a common ancestral origin and estimated the ages of these mutations. Haplotype analyses were performed in 188 individuals (100 index patients, 88 relatives) from Pakistani breast/ovarian cancer families, all harboring one of the 23 recurrent BRCA1 mutations, and 90 healthy controls. Six microsatellite markers (D17S800, D17S1801, D17S855, D17S1322, D17S1323, and D17S951) were analyzed. Mutation ages were estimated using DMLE+2.3 software. An identical haplotype of different length was found in families harboring the same BRCA1 mutation and suggested founder effects for all 23 mutations. Sixteen founder mutations were ethnicity-specific: 15 occurred in families of Punjabi background and one in a family of Pathan background. The remaining seven mutations occurred in families with two ethnic backgrounds. All BRCA1 founder mutations were estimated to have arisen approximately 147 to 159 generations ago. Our findings suggest founder effects for all 23 recurrent BRCA1 mutations. This knowledge allows the design and development of a cost effective local genetic testing strategy in Pakistan.

Increased YAP1 expression is significantly associated with breast cancer progression, metastasis and poor survival.

YAP1 plays a key role as a transcriptional coactivator in the Hippo pathway. Based on conflicting reports regarding YAP1 function in cancer, this study discerned its role in breast carcinogenesis. First, a systematic review of salient breast cancer studies targeting YAP1 dysregulation was performed. Additionally, freshly excised tumor specimens of approximately200 breast cancer patients were processed for quantification of YAP1 expression at mRNA and protein levels using quantitative PCR and immunohistochemistry, respectively. YAP1 expression was ninefolds higher in tumors versus controls and significantly associated with metastasis (p <0.05) and poor survival in Pakistani breast cancer patients. These findings establish the role of YAP1 overexpression in tumorigenesis and metastasis. Hence, YAP1 inhibition may be considered a possible therapeutic strategy.

Developing the Reliability and Validity of an Urdu Version-Self-Efficacy Scale for Breast Cancer Patients in Pakistan.

No suitable scale has been identified in literature that comprehensively measure self-efficacy of Pakistani breast cancer patients. The study aimed to develop a self-efficacy scale in Urdu language and determine its dimensions. The scale was developed with input from experts and literature. It was administered, in cross-sectional phase of two pilot studies, on breast cancer patients receiving chemotherapy. Post hoc internal consistency reliability was computed and principal component analysis (PCA) was performed. U-SES comprised 17 questions. PCA revealed a total of five factors explaining cumulative variance of 68.7%. These factors were self-confidence, faith, coping, optimism, and decision making. Post hoc internal consistency (Cronbach's alpha) value was high (∞ = 0.87). The self-efficacy scale has acceptable validity and reliability and has potential to obtain information related to self-efficacy of cancer patients receiving chemotherapy.

Association of miR-146α gene polymorphism and expression levels of its target protein RhoA in Pakistani breast cancer patients.

To assess the association of miR-146a and its target protein RhoA expression levels in breast cancer. The case-control study was conducted at Riphah International University, Islamabad, Pakistan, from March 2017 to November 2018, and comprised confirmed breast cancer cases and controls who were matched for age and ethnicity. Genotyping and expression profiling of archived samples was performed. Data was analysed using SPSS 22. Of the 590 subjects, 295(50%) each were cases and controls. Among the cases, there were 195(66%) Punjabis, 59(20%) Pathans and 41(14%) Kashmiris. The corresponding numbers among the controls were 198(67%), 58(19.7%) and 39(13.2%). The association between genotypes of the cases and controls was significant (p<0.05). Strong association was seen in dominant, recessive and allelic models (p=0.05). In Punjabi group the association was (p<0.00) significant, but this association was not significant in Kashmiri and Pathan groups (p>0.05). No association was found with the receptor status and miR-146a polymorphism. The miR-146a gene polymorphism rs2910164 G/C was found to have increased susceptibility to breast cancer at genotype and allelic levels.

Prevalence of BRCA1/BRCA2 frequent mutations in the Pakistani breast cancer patients.

Objectives: Breast cancer is the most common cause of death in women. 20% of breast cancer cases are due to the variations in the BRCA1/BRCA2 genes. Various variants of BRCA1/2 genes have been reported worldwide, which cause breast cancer by forming truncated proteins. In the current study, we aimed to find out the prevalence of mutations 1294DEL40, E1250X and 5382insC (BRCA1) and 2157DELG (BRCA2) in a case control cohort of Pakistani origin. Study Design: Case Control Study. Setting: Microbiology and Molecular Genetics University of Punjab, Lahore. Period: December 2017 to June 2018. Material &amp; Methods: Blood samples from 80 female breast cancer patients and 80 healthy females were taken. DNA was isolated from blood by manual method and genotyping was done by PCR-RFLP. Results: We found that for the 2157DELG mutation of the BRCA2 gene, homozygous mutant phenotype is present only in the cases at a frequency of 25% while the BRCA1 gene mutations were less common i.e., the E1250X mutation showed 6.6% prevalence in patients, and the 1294del40 and 5382insC mutations were absent in the current cohort. Conclusion: Despite of sample size limitation, this study provides information about the prevalence of some common mutations. In addition, clinical risk factors were also noted which are essential in risk assessment. We foresee that targeting of specific genetic variants restricted to a particular ethnic group would be more effective in the future therapeutic approaches for the prevention and cure of breast cancer.

Detection of novel infiltrating ductal carcinoma-associated BReast CAncer gene 2 mutations which alter the deoxyribonucleic acid-binding ability of BReast CAncer gene 2 protein.

BReast CAncer gene 2 (BRCA2), a tumor suppressor gene located on chromosome 13q, encodes a 384-kDa protein which activates homologous recombination pathway to repair ssDNA damage. Keeping in view the high prevalence of breast cancer in Pakistan and significant association of BRCA2 with breast cancer, this project was initiated to investigate the mutational status of BRCA2 in Pakistani breast cancer patients. For this purpose, blood samples of 45 individuals, including 24 female patients (infiltrating ductal carcinoma of breast), who visited Institute of Nuclear Medicine, Oncology and Radiotherapy Hospital and Ayub Medical Complex, Abbottabad, Khyber Pakhtunkhwa, and 21 normal female residents of the area were collected and processed to extract deoxyribonucleic acid (DNA). Different regions of BRCA2 exon 11 were amplified through polymerase chain reaction (PCR), and PCR-amplified products of one (NF45) normal sample and four cancerous (205BC, 215BC, 218BC, 222BC) samples were subjected to DNA sequence analysis. Analysis of retrieved sequences revealed one novel nonsense mutation in sample 205BC. The observed mutation (delA21587) shifted the normal frame of amino acid (N905I, T906L, K907R, E908N, L909F, H910M, E911K, T912Q, and D913T) in encoded mutant protein and converted L914 into premature termination codon. In case of sample 222BC, another novel substitution mutation (A>G24962) was observed, which altered codon of I (isoleucine) into the codon for M (methionine) at position 2040 in resultant mutant protein. The results reflect the unique mutational profile of BRCA2 in Pakistani infiltrating ductal carcinoma patients and suggest an extension of study on a large scale.

Association between Cyclooxygenase-2 and Indoleamine 2,3-Dioxygenase Expression in Breast Cancer Patients from Pakistan.

Background:Tumors use several immunosuppressive mechanisms to evade immune destruction. Cyclooxygenase-2 (COX-2) expression may be a driver of immunosuppression in breast cancer, but the mechanisms involved remain elusive. COX-2 expression induces the expression of indoleamine 2,3 dioxygenase (IDO) in tumor cells. IDO is an immunosuppressive enzyme which is involved in tumor immune escape mechanisms in breast cancer. Our aim was to evaluate the association between COX-2 and IDO expression to find evidence of immunosuppression in Pakistani breast cancer patients. Methods:Immunohistochemical analysis was performed to evaluate the expression of COX-2, IDO, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) on formalin-fixed paraffin-embedded breast cancer tissues of 100 patients. Univariable and multivariable logistic regression model was used to identify the independent risk factors of COX-2. Results:A total of 100 patients were included with a mean age and standard deviation of 48.28 ± 11.83. A significant association was observed among COX-2, IDO, ER, PR and tumor grade. In multivariable analysis, three variables were identified as significant independent risk factors for high COX-2: IDO expression high; [adjusted odds ratio (AOR) 6.51; 95% confidence interval (CI) (2.00-21.20), p=0.001], ER; [AOR 5.62; 95% CI (1.80-17.84), p=0.002] and age [AOR 1.04; 95% CI (1.00-1.10), p=0.05] respectively. Conclusion:Our data showed that high IDO expression is associated with high COX-2 expression in Pakistani breast cancer patients. The co-expression of both enzymes may suggest their role in disease pathogenesis. Hence the concurrent targeting of COX-2 and IDO may be a promising therapy for breast cancer.

Spectrum and prevalence of BRCA1/2 germline mutations in Pakistani breast cancer patients: results from a large comprehensive study

BackgroundPathogenic germline mutations in BRCA1 and BRCA2 (BRCA1/2) account for the majority of hereditary breast and/or ovarian cancers worldwide. To refine the spectrum of BRCA1/2 mutations and to accurately estimate the prevalence of mutation in the Pakistani population, we studied 539 breast cancer patients selected for family history and age of diagnosis.MethodsComprehensive screening for BRCA1/2 germline mutations was performed using state-of-the-art technologies.ResultsA total of 133 deleterious mutations were identified in 539 families (24.7%), comprising 110 in BRCA1 and 23 in BRCA2. The prevalence of BRCA1/2 small-range mutations and large genomic rearrangements was 55.4% (36/65) for families with breast and ovarian cancer, 27.4% (67/244) for families with two or more cases of breast cancer, 18.5% (5/27) for families with male breast cancer, and 12.3% (25/203) for families with a single case of early-onset breast cancer. Nine mutations were specific to the Pakistani population. Eighteen mutations in BRCA1 and three in BRCA2 were recurrent and accounted for 68.2% (75/110) and 34.8% (8/23) of all identified mutations in BRCA1 and BRCA2, respectively. Most of these mutations were exclusive to a specific ethnic group and may result from founder effects.ConclusionsOur findings show that BRCA1/2 mutations account for one in four cases of hereditary breast/ovarian cancer, one in five cases of male breast cancer, and one in eight cases of early-onset breast cancer in Pakistan. Our study suggests genetic testing of an extended panel of 21 recurrent BRCA1/2 mutations for appropriately selected patients and their families in Pakistan.

Identifying the reasons for delayed presentation of Pakistani breast cancer patients at a tertiary care hospital.

BackgroundDelay in seeking health care by breast cancer patients is associated with advanced stage of disease at presentation and poor survival rates. This study aimed to identify the reasons for delayed presentation and their association with various sociodemographic variables.MethodsA total of 200 female patients with abnormal clinical findings, ie, lump or palpable mass, were consecutively invited for this study. Diagnostic delay was defined as a consultation with a health care provider more than 3 months from the appearance of the first symptoms. Sociodemographic variables, presenting symptoms, knowledge about diseases and its symptoms, time between seeking medical attention after appearance of symptoms and causes of delayed presentation were investigated. Chi-squared and logistic regression tests for significance and associations were used.ResultsAmong 125 women with breast cancer fulfilling the inclusion criteria, aged 24–75 years, 88.8% (n=111) presented late (≥3 months) and 59% presented with advanced stage of disease (stage III/IV). The majority (65.6%) were older than 40 years of age, 99.2% were married, 60.8% had <8 years of education, 67.2% had poor social status, and 64.8% had a negative family history of any cancer type. Almost all patients (96%) complained about the presence of a painless lump in their breast. Ignorance of disease or the presence of painless lumps in the breast and low financial resources for therapy (81.1%) were the main variables associated with delayed presentation. Educational factors (P<0.001, OR 4.682) and social status (P<0.001, OR 1.8) were also associated with delayed presentation.ConclusionOur study highlighted the variables associated with delayed presentation in Pakistani breast cancer patients. A significant number of patients presented late owing to misconceptions and poor knowledge about the disease and its symptoms, while illiteracy and poor social status were the major contributing factors for delayed presentation, resulting in an advanced presentation of disease and ultimately a decreased survival rate.

Comparative study of adjuvant chemotherapeutic efficacy of docetaxel plus cyclophosphamide and doxorubicin plus cyclophosphamide in female breast cancer.

PurposeThis retrospective study presents a comparative analysis of the overall survival and toxicities, as side effects, of docetaxel plus cyclophosphamide (TC) and doxorubicin plus cyclophosphamide (AC). The study measured their efficacies during adjuvant chemotherapy, treating Pakistani breast cancer patients by validating the results obtained, with the published analysis of the same treatment given to US patients.Patients and methodsBetween June 2015 and September 2017, for four chemotherapy cycles, 189 patients out of 358 received TC (75 mg/m2 of docetaxel, 600 mg/m2 of cyclophosphamide) and 169 were treated with AC (60 mg/m2 of doxorubicin, 600 mg/m2 of cyclophosphamide). On the basis of using pathological markers to assess patients, toxicities, as side effects, (due to docetaxel, doxorubicin, and cyclophosphamide) were listed in the database of this study. Common factors with respect to common terminology criteria for adverse events version 5.0 and side effects listed in MedlinePlus, NIH US database, and from the database of this study were then separated to be included in comparison for this study. Statistically, chi-squared test was used at α=0.05.ResultsThere was no statistically significant difference between the proportions of patients with vomiting, extreme tiredness, diarrhea, mild anemia, stability, and overall survival because P-value >0.05. However, AC remained less toxic (P-value <0.05) by 22.6%, 25.7%, 25.3%, 12.4%, 20.8%, and 16.4% compared to TC for changes in taste, muscle pain, burning hands, change in hemoglobin level, moderate anemia, and needing blood transfusion respectively, whereas TC remained less toxic by 52.9%, 32.5%, and 26.3% for dizziness, weight loss, and sores in throat and mouth, respectively.ConclusionAt 27 months, TC was more toxic than AC, whereas both combinations had the same overall survival rate.

Identifying the Barriers of Delayed Presentation in Pakistani Breast Cancer Patients Undergoing Care at Tertiary Hospital

Background: Breast cancer is the most frequently diagnosed cancer in females worldwide and second leading cause of cancer related death among women. In Pakistan, 1 in 8 women would develop breast cancer at some stage of their life. Aim: Delay in seeking health care by breast cancer patients is associated with advanced stage of disease and poor survival rate. This study aimed at identifying the barriers of delayed presentation and their association with various sociodemographic variables. Methods: A total of 200 female patients with abnormal breast finding were randomly selected. Delay was defined as, consultation with health care provider by more than 3 months from the appearance of first symptoms. Sociodemographic variables, symptoms, time interval between seeking medical attention and appearance of symptoms and causes of the delayed presentation were inquired. Data were statistically evaluated by χ2 and logistic regression tests for significance and association. Results: Among 125 breast cancer women fulfilling inclusion criteria, aged 24-75 years, 88.8% (n = 111) of patients presented late (&gt;3 months) and 59% of them were presented advanced stage (stage III/IV) of disease. Majority of them were older than 40 years (65.6%) age, 99.2% married, 60.8% under matriculation, 67.2% had poor social status, 64.8% had a negative family history of any cancer type. 96% of patients complained presence of a painless lump in their breast. Ignorance of disease or presence of painless lumps in the breast and low financial resources for therapy (81.1%) were the main causes of delayed presentation. Moreover, educational factor ( P &lt; 0.000, OR, 4.682) and social status ( P &lt; 0.001, OR, 95% CI) were also associated with delayed presentation. Conclusion: Our study highlighted the reasons of delayed presentation in Pakistani breast cancer patients. The significant number of patients presented late due to misconceptions and poor knowledge about the disease and its symptoms while illiteracy and poor social status were the major contributing factors toward delayed presentation which lead to advanced stage of disease and ultimately decreased survival rate.