The relationship between phytoestrogen-rich supplements and breast cancer: A multicenter case-control study in Saudi Arabia.

Objectives: The prospective effect of phytoestrogen-rich supplements has been explored by many researchers in an attempt to reduce breast cancer (BC) risk worldwide. In Saudi Arabia, some widely used supplements have high phytoestrogen content. Therefore, we aimed to (1) assess the relationship between phytoestrogen supplements (PSs) that are widely used among women of Saudi Arabia and BC and (2) assess the relationship based on the menstrual status. Methods: The study took place during 2020-2022 to assess several PSs using a case-control design that included five centers from different provinces around the country. A questionnaire was answered by the participants that included 381 (46%) cases (diagnosed with BC) and 449 (54%) controls (free of BC). The PS items were assessed individually and on the multivariant analysis model. Results: Of the 12 phytoestrogen-rich supplements, soy milk showed a significant decrease in BC risk. However, Echinacea showed an increased risk of BC among its users. A subgroup analysis based on the menstrual status demonstrated an increased risk of BC among licorice root and green tea users on premenopausal and postmenopausal women, respectively. Conclusion: Soy isoflavones continue to show a significant risk reduction that could be used for a modified approach to reduce the risk of BC. However, Echinacea, licorice root, and green tea have shown to increase the risk of BC.

Juvenile Papillomatosis of the Breast: a Report of Two Cases with Review of the literature.

Background: Juvenile papillomatosis (JP) of the breast is a rare and benign proliferative disorder affecting young women. The affected patients tend to have an increased risk of breast cancer development during follow-up. Objective: This article aims to highlight a rare entity of breast disease, that harbor risk of breast cancer. Case Presentation: Here, we present 2 cases of JP in young females; the first case is a 13 year-old presented with spontaneous nipple discharge, while the other patient is a 24 year-old presented with a right breast lump. Both patients had a total excision of the breast lesions, revealing JP at histology. Discussion: Juvenile Papillomatosis is considered a clinicopathological entity and is usually misdiagnosed as fibroadenoma clinically and radiologically, which requires histological correlation. The histologic findings are well-defined (hyperplasia, papillomatosis, and multiple cysts with foamy histiocytes).The controversy in management between surgery and observation is because of insufficient knowledge about the direct relationship between JP and subsequent cancer. Conclusion: Considering the risk of developing breast cancer in JP, enrolling patients and their families in a close follow-up and surveillance program is crucial.

Alternative splicing is an important mechanism behind KAI1 loss of function in breast cancer patients from Saudi Arabia.

PURPOSE: KAI1 (also called CD82) is a metastasis suppressor gene known to be downregulated in breast cancer and other solid tumors. The downregulation of KAI1 or loss of its function is usually associated with bad prognosis. The mechanism behind KAI1 loss of function is complex. In this study, we investigated "alternative splicing" as a possible mechanism that underlies KAI1 loss of function in breast cancer patients from a tertiary hospital in Saudi Arabia. METHODS: Expression of KAI1 was studied in FFPE breast cancer and control tissue sections by IHC using two different antibodies targeting different domains of the protein. The TS82B antibody targets the extracellular loop, which constitutes most of the protein, while the second EPR4112 antibody targets the C-terminal intracellular domain of the protein. RESULTS: Out of 90 breast cancer samples, 67% showed loss of KAI1 expression. The remaining 33% showed KAI1 expression with (TS82B) antibody; however, the protein was detected in only 11% of cancers when using the antibody (EPR4112) indicating a truncation of the protein at the C-terminus (truncated-KAI1) in 22% of the studied cancer samples. A significant correlation was found between truncated-KAI1 expression and advanced cancer stage (association with lymph node metastasis, P value 0.008). CONCLUSION: Alternative splicing is an important mechanism underlying KAI1 loss of function in breast cancer, and it is associated with bad prognosis (advanced cancer stage).

A Germline Mutation in the BRCA1 3'UTR Variant Predicts Susceptibility to Breast Cancer in a Saudi Arabian Population

Purpose: The impact of the BRCA1-3'UTR-variant on BRCA1 gene expression and altered responses to external stimuli was previously tested in vitro using a luciferase reporter assay. Its ability to predict breast cancer risk in women was also assessed but the conclusions were inconsistent. The present study concerns the relationship between the BRCA1-3'UTR germline variant rs8176318G>T and susceptibility to Breast cancer in an ethnic population of Saudi Arabia. Methodology: The study included 100 breast cancer patients and 100 sex matched healthy controls from the northwestern region (Tabuk) and Dammam of Saudi Arabia were investigated for the BRCA1-3'UTR germline variant rs8176318G>T using an allele specific PCR technique. Genotype distributions were then compared. Results: The frequencies of the three genotypes GG, TT and GT in our Saudi Arabian patients were 26%, 8% and 66% and in healthy controls were 45%, 5% and 50%, respectively (p=0.03). Risk of developing breast cancer was found to be significantly associated with the GT variant (OR 2.28, 1.24-4.191; RR 1.47, 1.11-1.93; P=0.007), GT+TT (OR, 2.32, 1.28-4.22; RR 1.48, 1.13-1.94; P=0.005) and the T allele (OR 1.62 , 1.072- 2.45; RR 1.28, 1.02-1.60: P=0.020). There were 2.76 and 2.28 fold increase risks of developing breast cancer associated with the TT and GT genotypes in our cases. A significant correlation was also found between the BRCA1 3'UTR variants with the stage of the disease and distant metastasis but not with age, grade, and ER, PR and her2/neu status. Conclusion : The rs8176318G/T in the 3'untranslated region (UTR) of the BRCA1 gene was found to be associatedwith increased susceptibility to breast cancer in our study population, increased risk being noted with the GT and TT genotypes. Further association studies are needed to confirm this finding in other regions of Saudi Arabia.

Rethinking: Ideal Screening Age for Breast Cancer in Developing Countries.

OBJECTIVE: The aim is to identify the ideal screening age for women in developing countries and to determine the suitable method for early detection of breast cancer based on age and readiness of the community. MATERIALS AND METHODS: A 30-year retrospective review (from 1984 to 2014) was undertaken at King Fahd Hospital of the University, Al-Khobar, Saudi Arabia. Medical records of those diagnosed with breast cancer from the outpatient department and hospital admission records were reviewed, focusing mainly on demographic data, age, and time at presentation. Radiological and histopathological records were also reviewed for confirmation of diagnosis. Age-based statistical review was undertaken of the female population within the hospital catchment area. RESULTS: The total number of patients was 1.832, accounting for 0.8 % affected patients when plotted against the 235,339 females within the catchment area. Considering the standard screening age of 40 years, patients were divided into two groups: group I included those below the age of 40 years at the time of diagnosis, accounting for 641patients (35%), and group II included those above the age of 40 years, accounting for 1191 patients (65%). Group I patients were mostly reassured in primary healthcare centers, diagnostic modalities were used with reservation, relying solely on ultrasonography 276 (43%); whereas in group II patients, mammography was used liberally, which aided in the diagnosis in all 1191 (100%). CONCLUSION: Despite the undisputable notion that breast cancer has higher predilection for women above the age of 40 years, there is a substantial subset of affected younger women in developing countries, which contradicts this concept. However, the scarcity of structured sessions in developing countries dictates Western-based early detection strategies, but the validity of such programs is culture-governed. Rigorously tailored screening programs directed towards individual communities are mandatory. Reducing the screening age by a decade in developing countries may increase the capture of early breast cancer and improve the outcomes.

Distribution of molecular breast cancer subtypes in middle eastern-saudi arabian women: a pilot study.

Increasing evidence suggests the possibility of relevant molecular differences between cancers from different ethnic groups. This study uses gene expression profiling by quantitative real time polymerase chain reaction (qRT-PCR) to identify "intrinsic" subtypes in a Saudi population of breast cancers and compares the distribution of subtypes to the more commonly profiled Caucasian population. In addition, the immunohistochemical profile of breast cancers was correlated to the gene expression analysis. Discrepancy rate of 39% in subtype prediction between gene expression and immunohistochemical profile of the tumors was noticed. Most of this variation was in the luminal subtype. Frequency of HER2+ subtype in the Saudi cases was high (28%) by both the immunohistochemistry (IHC) and the qRT-PCR classification. Triple-negative tumors comprised 39% while only 11% showed a basal-like profile. Analysis of larger cohort of patients is needed to determine the molecular taxonomy of breast cancer in the Saudi population and the benefits from the diagnostic classification developed in the West.