Trial Id: The Study of Quadruple Therapy Quercetin, Zinc, Metformin, and EGCG as Adjuvant Therapy for Early, Metastatic Breast Cancer and Triple-negative Breast Cancer, a Novel Mechanism Recruitment Status: Not yet recruiting Trail description: breast cancer is the most common cancer in women. With more than 1 in 10 new cancer diagnoses each year, It is the second most frequent cancer-related death among women worldwide. Breast cancer develops slowly, and the majority of cases are found through routine screening.

breast cancer-causing deaths among women all over the world and increased in the last few years even though the treatment is advanced like immunotherapy chemotherapy by yet no treatment for triple-negative breast cancer zinc and competition between znt1 and zip6,10 at breast cancer cells. Is zinc ionophore like quercetin and EGCG has a role, In a novel experimental study zinc is a trace metal that has many roles in cells, enzymatic activity, and gene regulations, and also for the integrity of DNA.

Zinc transporters (zinc related -proteins such as ZIPs, and ZnTs are affected by triggers factors like cytokines and growth factors.

There are two large families of zinc transporters like ZIPs ( 14 members) and ZnTs family (10 members), ZIPS family cause an influx of zinc from the extracellular to the cytoplasm and also from intracellular organelles like endoplasmic reticulum or Golgi or mitochondria in contrast to ZnTs which cause an influx of zinc from the cytoplasm to intracellular organelles. ( lower cytoplasmic zinc) (1) Breast cancer deaths occurred from metastasis; Catalytic enzymes called proteases like cathepsin L are frequently overexpressed in aggressive cancers. Breast tumor metastatic potential is correlated with macrophage presence. These macrophages associated with tumors frequently adopt an M2-like pro-tumorigenic phenotype, which results in the production of growth hormones and proteases, notably the lysosomal protease cathepsin L. Because cathepsin L is commonly released by breast cancer cells and aids in tumor invasion, metastasis, and angiogenesis. It is expected that cathepsin L secretion by both tumor-associated macrophages and neoplastic cells would promote the metastatic phenotype because cathepsin L is widely produced by breast cancer cells and helps with tumor invasion, metastasis, and angiogenesis. (2) this study target new mechanisms and achieves the best management as some types of cancer breast like triple-negative breast cancer (TNBC) no definite treatment so we target the following pathways and epigenetic processes by these adjuvant compounds which have a promising role in the immunity like EGCG, Quercetin, Zinc, Metformin so our team will discuss novel methods to achieve the best efficacy from chemotherapy Inclusion Criteria: Age above 18
Female patients
with any type of breast cancer Ductal carcinoma in situ (DCIS) ... Invasive breast cancer (ILC or IDC) ... Triple-negative breast cancer. ... Inflammatory breast cancer. ... Paget disease of the breast. ... Angiosarcoma. ... Phyllodes tumor.
HER2-positive by ASCO CAP 2018 guidelines, confirmed by central testing
Participants must have normal organ and marrow function as defined below:

ANC ≥ 1000/mm3 hemoglobin ≥8 g/dl platelets ≥ 75,000/mm3 AST and ALT both <5x institutional ULN Total bilirubin ≤ 1.5 mg/dL. For patients with Gilbert syndrome, the direct bilirubin should be <institutional ULN Serum creatinine ≤ 2.0 mg/dL OR calculated GFR ≥ 30mL/min 6- Locally advanced tumors at diagnosis, including tumors fixed to the chest wall, peau d'orange, skin ulcerations/nodules, or clinical inflammatory changes (diffuse brawny cutaneous induration with an erysipeloid edge) Patients with a history of previous invasive breast cancer.

- Exclusion Criteria: Neoadjuvant or adjuvant chemotherapy for this breast cancer prior to enrollment is prohibited.

Any of the following due to teratogenic potential of the study drugs:

Pregnant women Nursing women Women of childbearing potential who are unwilling to employ adequate contraception (condoms, diaphragms, IUDS, surgical sterilization, abstinence, etc). Hormonal birth control methods are not permitted.

Participants who are receiving any other investigational agents for treatment of breast cancer, unless specific approval is obtained from the Sponsor-Investigator.

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