Circulating HER‑2 mRNA in the peripheral blood as a potential diagnostic and prognostic biomarker in females with breast cancer

Abstract

Breast cancer is a prevalent malignant cancer worldwide, and a lack of defined biomarkers for early prognostication contributes to its high associated mortality rate, especially in human epidermal growth factor receptor 2 (HER-2)-positive breast cancer. In the present study, HER-2 mRNA levels in patients were detected prior to surgery and during neoadjuvant chemotherapy to explore its potential diagnostic and prognostic value. Blood samples were collected from 70 patients with breast cancer, including 50 HER-2-negative and 20 HER-2-positive patients, prior to and following surgery (postoperative, n=13; neoadjuvant chemotherapy, n=5); the control group included 35 samples from healthy individuals. The relative mRNA level of HER-2 in blood was determined by one-step reverse transcription-quantitative polymerase chain reaction. HER-2 expression curves of measurements taken during neoadjuvant chemotherapy were compared with the tumor size. A significant difference in the blood HER-2 mRNA level was observed between healthy women and patients with breast cancer (P<0.0001). A cutoff value of 1.512 was established for the circulating HER-2 level in healthy subjects based on the upper 95% confidence interval value of samples from the control group. The level of HER-2 mRNA in blood was associated with the HER-2 status, Ki-67 expression, and lymphovascular invasion in primary tumor tissue samples; however, there was no association with the lymph node status, tumor stage, tumor grade, tumor size, patient age, estrogen or progesterone receptor status of the primary tumor. HER-2 mRNA levels were associated with the response rate, as determined by primary tumor size, in patients who received neoadjuvant chemotherapy. In conclusion, baseline and early changes in peripheral blood HER-2 mRNA indicated that HER-2 mRNA may be a potential diagnostic biomarker for breast cancer and a prognostic marker for predicting the efficacy of neoadjuvant therapy.

<p>ATF3 Demethylation Promotes the Transcription of ARL4C, Which Acts as a Tumor Suppressor in Human Breast Cancer</p>

“…1 Breast cancer subtypes include ER+, PR+, HER2+, and triple negative breast cancer (TNBC). 2,3 Improvements have been made in early screening, diagnosis, and targeted therapy, but the detailed mechanisms of development of breast cancer are not well-characterized. Characterization of the molecular basis of breast cancer, and identification of reliable biomarkers, are critical to improvement of early diagnosis and treatment.…”

Cancer Biomarkers in Liquid Biopsy for Early Detection of Breast Cancer: A Systematic Review

“…In addition, 2 articles studied only patients with triple-negative BC, 101,116 and 2 included patients with HER2-enriched BC. 76,95 In reference to the disease stage, 57.4% of the articles detailed the stages that the patients were in at the time. In 43 articles, patients in all stages (I, II, III, and IV) were included, representing a population of 5382 patients with BC (stage II was the most frequent, representing 3230 patients).…”

“…The expressions obtained from cfDNA originate from tumor cells that detach from a tumor at an advanced stage of its development. 154 In 29 articles, [23][24][25]28,59,60,68,73,79,80,85,89,92,95,96,99,103,105,108,109,115,117,119,121,126,128,129,136,141 sensitivity and specificity were reported individually for a single biomarker. In 21 of these, sensitivity was greater than 70%.…”

“…Abbreviations: BC, breast cancer; HER2, human epidermal growth factor 2; LB, liquid biopsy. As shown in Table 6, highlighted in gray, 28 biomarkers presenting a Sensitivity greater than 90% were identified: miR-17-5p, miR-155, miR-222, 89 miR-202, 60 PTEN, SMAD4, 24 APC, RARB2, 115 miRNA-222, miRNA-373, 92 miR-27a, 85 cfDNA methylation score, 25 HER2 mRNA, 95 miR-21, 28 polymorphism -31G/C in survivin promoter gene, 79 hsa-miR25-3p, hsa-miR-548ar-5p, 80 miR-598-3p, miR-1246, 105 miR-495, 117 telomeric sequences in cfDNA, 121 miR-30c, miR-148a, 39 miR-185-3p, 49 miR-34a, 17 miR10b, miR21, 12 and miRNA-373. 34 As shown in Table 7, highlighted in gray, 16 biomarker panels in peripheral blood can be observed 19,22,27,29,30,42,44,54,61,81,93,98,106,111,112,123 and 2 biomarker panels in saliva 74,86 with a sensitivity greater than 90%.…”

Atezolizumab Plus Chemotherapy vs. Chemotherapy in Advanced or Metastatic Triple-Negative Breast Cancer: A Cost-Effectiveness Analysis

“…Molecular markers depend primarily on the expression of relevant receptors in breast cancer, including estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). Various expressions of these receptors classified into major subtypes include luminal A, luminal B, HER2-overexpressing and triple-negative breast cancer (TNBC) (4)(5)(6). TNBC, an intrinsic subtype of breast cancer, is defined as a tumor that does not express the ER, PR, or HER2 and accounted for 15-20% of all breast cancer cases.…”