microRNA-related single-nucleotide polymorphisms and breast cancer. Farbod Bahreini, Elham Rayzan, Nima Rezaei  –  Cell Physiol. 2020 Jul 27.

Breast cancer, as the most common cancer in women which affects patients both mentally and physically, requires great attention in many areas and many levels as this cancer is known to be multifactorial. Single-stranded molecules called microRNAs with near 22 nucleotides are seen to act in central dogma of molecular biology by inhibiting the translation process; it is demonstrated that any alteration in their sequence especially single-nucleotide polymorphisms (SNPs) may lead into increasing the breast cancer risk. miR-SNPs are considered to be the potential biomarkers for early detection of breast cancer. As a result, this review documents the well-known miR-SNPs that are known to be associated with breast cancer. In this regard, two principals were discussed: (a) SNPs in the target genes of microRNAs and the alteration in gene expression due to this phenomenon; (b) changes based on the SNPs in the microRNA coding region and the impact on their interaction with target messenger RNA.

The prognostic and predictive role of 21-gene recurrence scores in hormone receptor-positive early-stage breast cancer. Shahid Ahmed, Sukanya Pati , Duc Le et Al –   Surg Oncol. 2020 Aug;122(2):144-154

Over the past two decades, gene expression profiling of breast cancer has emerged as an important tool in early-stage breast cancer management. The approach provides important information on underlying biological mechanisms, breast cancer classification, future risk potential of developing recurrent metastatic disease, and provides beneficial clues for adjuvant chemotherapy in hormone receptor (HR) positive breast cancer. Of the commercially available genomic tests for breast cancer, the prognostic and predictive value of 21-gene recurrence score tests have been validated using both retrospective data and prospective clinical trials. In this paper, we reviewed the current evidence on 21-gene expression profiles for HR-positive HER2-negative early-stage breast cancer management. We show that current evidence supports endocrine therapy alone as an appropriate adjuvant systemic therapy for approximately 70% of women with HR-positive, HER2-negative, node-negative breast cancer. Evolving evidence also suggests that 21-gene recurrence scores have predictive values for node-positive breast cancer and that chemotherapy can be avoided in more than half of women with nodes 1 to 3 positive HR-positive breast cancer. Furthermore, retrospective data also supports the predictive role of 21-gene recurrence scores for adjuvant radiation therapy. A prospective trial in this area is ongoing.

Gene panel screening for insight towards breast cancer susceptibility in different ethnicities. Madison R Bishop, Sophonie M Omeler-Fenaud  Et Al. –  PLoS One. 2020 Aug 31;15(8):e0238295

African American breast cancer genetics is less understood compared to European American breast cancer susceptibility. Despite the many advantages of gene panel screening, studies investigating African American inherited breast cancer risk and comparing variant contributions between ethnicities are infrequent. Thus, 97 breast cancer-affected individuals of African and European descent from the Alabama Hereditary Cancer Cohort were screened using the research-based gene-panel, B.O.P. (Breast, Ovarian, and Prostate cancer). Upon sequencing and bioinformatic processing, rare coding variants in 14 cancer susceptibility genes were categorized according to the American College of Medical Genetics guidelines and compared between ethnicities. Overall, 107 different variants were identified, the majority of which were benign/likely benign. A pathogenic/likely pathogenic variant was detected in 8.6% and 6.5% of African American and European American cases, respectively, which was not statistically significant. However, African Americans were more likely to have at least one variant of uncertain significance (VUS; p-value 0.006); they also had significantly more VUSs in BRCA1/2 compared to European Americans (p-value 0.015). Additionally, 51.4% of African Americans and 32.3% of European Americans harbored multiple rare variants, and African Americans were more likely to have at least one VUS and one benign/likely benign variant (p-value 0.032), as well as multiple benign/likely benign variants (p-value 0.089). Moreover, of the 15 variants detected in multiple breast cancer cases, ATM c.2289T>C (p.F763L), a VUS, along with two likely benign variants, BRCA2 c.2926_2927delinsAT (p.S976I) and RAD51D c.251T>A (p.L84H), were determined to be associated with African American breast cancer risk when compared to ethnic-specific controls. Ultimately, B.O.P. screening provides essential insight towards the variant contributions in clinically relevant cancer susceptibility genes and differences between ethnicities, stressing the need for future research to elucidate inherited breast cancer risk.

Aspirin might reduce the incidence of breast cancer: An updated meta-analysis of 38 observational studies. Yueqing Cao 1, Aihua Tan Medicine (Baltimore). 2020 Sep 18;99(38):e21917.

Background: Many epidemiologic studies were performed to clarify the protective effect of regular aspirin use on breast cancer risks, but the results remain inconsistent. Here, we conducted an updated meta-analysis of 38 studies to quantitatively assess the association of regular aspirin use with risk of breast cancer.

Method: We performed a bibliographic database search in PubMed, Embase, Web of Science, Cochrane library, Scopus, and Google Scholar from January 1939 to December 2019. Relative risk (RR) estimates were extracted from eligible case-control and cohort studies and pooled using a random effects model. Subgroup analysis was conducted based on study design, aspirin exposure assessment, hormone receptor status, menopausal status, cancer stage as well as aspirin use duration or frequency. Furthermore, sensitivity and publication bias analyses were performed.

Results: Thirty eight studies of 1,926,742 participants involving 97,099 breast cancer cases contributed to this meta-analysis. Compared with nonusers, the aspirin users had a reduced risk of breast cancer (RR = 0.91, 95% confidence interval [CI]: 0.87-0.95, P value of significance [Psig] < .001) with heterogeneity (P value of heterogeneity [Phet] < .001, I = 82.6%). Subgroup analysis revealed a reduced risk in case-control studies (RR = 0.83, 95% CI: 0.78-0.89, Psig < .001), in hormone receptor positive tumors (RR = 0.91, 95% CI: 0.88-0.94, Psig < .001), in situ breast tumors (RR = 0.79, 95% CI: 0.71-0.88, Psig < .001), and in postmenopausal women (RR = 0.89, 95% CI: 0.83-0.96, Psig = .002). Furthermore, participants who use aspirin for >4 times/wk (RR = 0.88, 95% CI: 0.82-0.96, Psig = .003) or for >10 years (RR = 0.94, 95% CI: 0.89-0.99, Psig = .025) appeared to benefit more from the reduction in breast cancer caused by aspirin.

Conclusions: Our study suggested that aspirin use might be associated with a reduced risk of breast cancer, particularly for reducing the risk of hormone receptor positive tumors or in situ breast tumors, and the risk of breast cancer in postmenopausal women.

Association of Insulin, Metformin, and Statin with Mortality in Breast Cancer Patients. Mihong Choi, Jiyeon Han, Bo Ram Yang et Al. – Cancer Res Treat. 2020 Sep 23.

Purpose: This study investigated the association of insulin, metformin, and statin use with survival and whether the association was modified by the hormone receptor status of the tumor in patients with breast cancer.

Materials and methods: We studied 7,452 patients who had undergone surgery for breast cancer at Seoul National University Hospital from 2008 to 2015 using the nationwide claims database. Exposure was defined as a recorded prescription of each drug within 12 months before the diagnosis of breast cancer.

Results: Patients with prior insulin or statin use were more likely to be older than 50 years at diagnosis and had a higher comorbidity index than those without it (p < 0.01 for both). The hazard ratio (HR) for death with insulin use was 5.7 (p < 0.01), and the effect was attenuated with both insulin and metformin exposure with an HR of 1.2 (p=0.60). In the subgroup analyses, a heightened risk of death with insulin was further prominent with an HR of 17.9 (p < 0.01) and was offset by co-administration of metformin with an HR of 1.3 (p=0.67) in patients with estrogen receptor (ER)-negative breast cancer. Statin use was associated with increased overall mortality only in patients with ER-positive breast cancer with HR for death of 1.5 (p=0.05).

Conclusion: Insulin or statin use before the diagnosis of breast cancer was associated with an increase in all-cause mortality. Subsequent analyses suggested that metformin or statin use may have been protective in patients with ER-negative disease, which warrants further studies.

Breast cancer early detection: Role of circulating plasma miRNA-21 expression as a potential screening biomarker. Muhammad Noor Diansyah, Ami Ashariati Prayogo, Made Putra Sedana et Al. – Turk J Med Sci. 2020 Sep 20.

Aim: To explore the circulating plasma miRNA-21 potential as early detection biomarker by comparing early-stage breast cancer (BG) and healthy control (HG) in Indonesian population.

Materials and methods: The enlisted patients were twenty-six adult female early-stage breast cancer patients (stage 1A, 1B, 2A and 2B) of Airlangga University Hospital from August until October 2019. Sixteen volunteers were recruited as matched healthy subjects. MiRNA-21 expression was quantified by plasma qRT-PCR. Data analysis performed using IBM SPSS Statistics v.24. MiRNA-21 cut-off, sensitivity, and specificity were analyzed using receiver operating characteristic (ROC) curve.

Results: The subject includes 26 BG and 16 HG subjects. The miRNA-21 expression in BG group was 3.933 (1.181-11.794) and 0.905 (0.164-4.532) in HG group (4.34 folds; p=0.001), with 1.66 cut-off (92.3% sensitivity; 81.2% specificity). MiRNA-21 expression separated analysis in HG showed a 0.578 times lower expression in menopause subjects [0.651 (0.164-0.414)] compared to pre-menopause [(1.123 (0.758-4.532); p=0.031]. Yet, in BG group 1.729 times higher miRNA-21 expression was observed in menopause subjects (6.021±3.583) compared to pre-menopause subjects (3.500±1.517;p=0.022).

Conclusion: Circulating miRNA-21 expression is a potential biomarker for early detection of breast cancer and might act as a breast cancer risk predictor. Key words: Biomarkers, breast neoplasms, diagnosis, human plasma, miRNA-21.