Quantum Dots: Synthesis, Antibody Conjugation, and HER2-Receptor Targeting for Breast Cancer Therapy

Breast cancer is becoming one of the main lethal carcinomas in the recent era, and its occurrence rate is increasing day by day. There are different breast cancer biomarkers, and their overexpression takes place in the metastasis of cancer cells. The most prevalent breast cancer biomarker is the human epidermal growth factor receptor2 (HER2). As this biomarker is overexpressed in malignant breast tissues, it has become the main focus in targeted therapies to fight breast cancer. There is a cascade of mechanisms involved in metastasis and cell proliferation in cancer cells. Nanotechnology has become extremely advanced in targeting and imaging cancerous cells. Quantum dots (QDs) are semiconductor NPs, and they are used for bioimaging, biolabeling, and biosensing. They are synthesized by different approaches such as top-down, bottom-up, and synthetic methods. Fully human monoclonal antibodies synthesized using transgenic mice having human immunoglobulin are used to target malignant cells. For the HER2 receptor, herceptin® (trastuzumab) is the most specific antibody (Ab), and it is conjugated with QDs by using different types of coupling mechanisms. This quantum dot monoclonal antibody (QD-mAb) conjugate is localized by injecting it into the blood vessel. After the injection, it goes through a series of steps to reach the intracellular space, and bioimaging of specifically the HER2 receptor occurs, where apoptosis of the cancer cells takes place either by the liberation of Ab or the free radicals.

Looking for more reliable biomarkers in breast cancer: Comparison between routine methods and RT-qPCR

Purpose Decades of quality control efforts have raised the standards of immunohistochemistry (IHC), the principle method used for biomarker testing in breast cancer; however, computational pathology and reverse transcription quantitative PCR (RT-qPCR) may also hold promise for additional substantial improvements. Methods Herein, we investigated discrepancies in the assessment of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and marker of proliferation Ki67 comparing routinely obtained IHC (and FISH) data (ORI) with the results of manual (REV) and semi-automated (DIA) re-evaluation of the original IHC slides and then with RNA expression data from the same tissue block using the MammaTyper® (MT) gene expression assay. Results Correlation for ER and PR was high between ORI IHC and the other three study methods (REV, DIA and RT-qPCR). For HER2, 10 out of 96 discrepant cases can be detected between ORI and REV that involved at least one call in the equivocal category (except for one case). For Ki67, 22 (29.1%) cases were categorized differently by either REV alone (n = 17), DIA alone (n = 15) or both (n = 10) and 28 cases (29.2%) for RT-qPCR. Most of the discrepant Ki67 cases changed from low to high between the original and following assessment and belonged to the intermediate Ki67 expression range (between 9 and 30%). Conclusions Determination of the breast cancer biomarkers ER, PR, HER2 and Ki67 at the mRNA level shows high degree of correlation with IHC and compares well with correlations between original with subsequent independent manual or semi-automated IHC assessments. The use of methods with wider dynamic range and higher reproducibility such as RT-qPCR may offer more precise assessment of endocrine responsiveness, improve Ki67 standardization and help resolve HER2 cases that remain equivocal or ambiguous by IHC/FISH. In summary, our findings seem to configure RT-qPCR as a complementary method to be used in cases of either equivocal results or presenting, at the traditional determination assays, biomarkers expressions close to the cut-off values.

A Review of Literature on Updates of Bisphosphonates Administration, Cancer Biomarkers for Bisphosphonate Therapy, and Bisphosphonate-related Osteonecrosis of the Jaw in Breast Cancer

Context: The emergence of bone health maintenance in breast cancer patients is known as an indispensable aspect in survival and morbidity improvement; therefore, bisphosphonates play a substantial role in the prevention/delaying of cancer treatment induced bone loss and skeletal-related events (SREs) in these patients, although this drug can cause necrosis of the jaw. In this article, we aimed at summarizing updated evidence on bisphosphonates administration, biomarkers representative of the efficacy of bisphosphonate therapy, and bisphosphonate-related osteonecrosis of the jaw (BRONJ) affection in patients involved in breast cancer. Methods: Associated published articles were searched for in EMBASE, MEDLINE, CDSR, PubMed, Google Scholar, and CINAHL, using the following keywords or, in the case of PubMed database, medical subject headings (MeSH): ‘Diphosphonate’, ‘osteonecrosis’, ‘breast cancer’, and ‘biomarker’ in the abstract or title, and was limited by "clinical trials, meta-analysis and randomized controlled trial” published in English language from 2015 to 2020-09-15. Results: Bisphosphonates depicted remarkable advantages in improving SREs, skeletal morbidity rate (SMR), survival rate, and treatment-emergent adverse events in breast cancer patients in almost all aspects of breast cancer therapy, from adjuvant therapy for the early stage breast cancer to bone metastatic breast cancer (BMBC). The identification of breast cancer biomarkers that are capable of reflecting the outcomes of bisphosphonates therapy is a highly advantageous aid in the optimal utilization of these drugs. Breast cancer biomarkers such as MAF, DOCK4, CD73, TLR9, and CAPG/GIPC1 composite illustrated a significant correlation with bisphosphonates administration. Medication-related osteonecrosis of the jaw (MRONJ) stands out as the most hazardous adverse event of the bisphosphonates with a rationally high incidence among breast cancer patients, which requires cautious prescription of bisphosphonates as well as regular dental health counseling for being prevented. Conclusions: Bisphosphonates are great weapons in the arsenal of breast cancer treatment and, therefore, comprehensive studying of their features leads to the optimal and safe administration of them. Unfortunately, as this procedure can cause necrosis of the jaw, dental procedures should be performed in these patients before starting bisphosphonate treatment.