Prevalence of Breast Cancer Subtypes Among Different Ethnicities and Bangladeshi Women: Demographic, Clinicopathological, and Integrated Cancer Informatics Analysis

Abstract

Background: The molecular subtyping of breast cancer is related to estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). The present study aimed to systematically analyze the expression, function, and prognostic value of ER, PR, HER2, and their prevalence in different ethnic groups and among Bangladeshi breast cancer (BC) patients.

Method: This study included 25 BC patients and 25 healthy controls, aged between 25 and 70 years. The study characteristics were compared using the ANOVA and Chi-square tests. Also, the multi-Omics dataset of 775 BC patients from TCGA was analyzed for ER, PR, and HER2 in breast cancer subtypes and compared among different ethnicities.

Results: For most BD breast cancer cases, the age at diagnosis was ⩾40 years, had only a histopathological diagnosis (P-value .004), and no history of mammography or other pathological tests. For treatment, had only chemotherapy (P-value .004) and no hormone therapy (P-value <.001). The majority of patients (>60%) were of stage-II cancer and TNBC (40%) subtype. The BC ethnicity-stratified data of ER, PR, and HER2 indicated a strong correlation across all ethnicities (P-value 4.99e-35; P-value 3.79e-18). The subtypes stratified data indicated a higher percentage of Luminal A (58.3%) in Caucasians whereas Luminal B (24.3%) and HER2 (25.2%) subtypes were found higher in Asians and TNBC (36.0%) were found in Africans. However, a significantly higher frequency of TNBC (52.2%) compared to Asians (14.8%) was found in BD patients (P-value <.001). The overall survival analysis of BC subtypes demonstrated that Luminal B (P-value .005) and HER2 enriched (P-value .015) were significantly more aggressive and were dominant in the Asian population.

Conclusion: A significant association was found between BC subtypes with different ethnicities and Bangladeshi women and these findings might aid in the prevention, management, and raising of awareness against risk factors in the near future.

Keywords: Breast cancer; TCGA; cBioPortal; estrogen receptor (ER); human epidermal growth factor receptor 2 (HER2); luminal A; luminal B; progesterone receptor (PR); subtypes; survival analysis; triple-negative breast cancer (TNBC).

Figure 1.

Flow chart of the data screening, selection, and retrieval of breast invasive carcinoma from TCGA, Pan-Cancer Atlas.

Figure 2.

ER, PR, and HER2 mRNA expression data stratified by different ethnicity/race categories. (A) Fraction genome altered versus mutation count correlation plot. (B) Bar plot of alteration event frequency (%) for the genetic subtypes of ER, PR, and HER2 receptors in different races. (C) Putative copy number alterations from GISTIC.

Figure 3.

ER, PR, and HER2 expression analysis in TCGA Tumor/Normal GTEx expression datasets. (A) Fraction genome altered in different races by BC subtypes, (B) compared the expression status of ER, PR, and HER2 in the TCGA breast cancer (BC) dataset with the corresponding normal tissues of the GTEx datasets, and (C) correlation analysis plot of ER, PR, and HER2 expression in TCGA. A P-value <.05 was considered significant.

Figure 4.

Survival analysis outcome in patients by breast cancer (BC) subtypes. (A) The stack bar plot of breast cancer (BC) subtypes expression data in different races with P and q values. (B) Kaplan-Meier plots of overall survival (OS) difference in patients by cBioPortal. Note that the different survival characteristics were of different datasets.

Figure 5.

(A) Tissue image differences in patients with different subtypes by immunohistochemistry (IHC). (B) Correlation analysis between mRNA expression, RSEM and protein expression, RPPA data of ER, PR, and HER2 receptors in Asian ethnicity.

Figure 6.

(A) Box plot for putative copy number alteration (CNA) versus mRNA expression of ER, PR, and HER2 in Asian ethnicity from GISTIC. (B) 3D structure of ER, PR, and HER2 with mutations (Green: missense; Blue: truncated; Brown: inframe; Orange: spliced; and Pink: fusion) and some single nucleotide polymorphisms (SNPs).