The purpose of this study was to retrospectively investigate the response to trastuzumab in breast cancer patients in terms of the potential roles of several oncogenic pathways (phosphatase and tensin homolog (PTEN) and phosphatidylinositol 3-kinase (PI3K)) in relation to HER2 status.
Several compounds in the series demonstrated potent growth inhibition in a PTEN-deficient breast cancer cell line MDA-MB-468 under anchorage independent conditions.
Hereditary breast cancer is characterized by an inherited susceptibility to breast cancer on basis of an identified germline mutation in one allele of a high penetrance susceptibility gene (such as BRCA1, BRCA2, CHEK 2, TP53 or PTEN).
Six genes showed PTEN-SSL patterns of activity in a large proportion of PTEN-deficient breast cancer cell lines and are potential specific vulnerabilities in PTEN-deficient breast cancer.
The aim of this research was to investigate the correlation of immunologic factors in the tumor environment of breast cancer, using immunohistological staining to evaluate the expression of programmed death 1/programmed death ligand 1 (PD-1/PD-L1), phosphatase and tensin homolog (PTEN), tumor infiltrating lymphocytes (TILs), and macrophages, and to analyze the association between the immunologic factors and clinical outcome for patients with early stage breast cancer (EBC).
Some of the tagging single-nucleotide polymorphisms of 5 genes ( PALB2, TP53, Nijmegen breakage syndrome 1, PTEN, and BRCA1-interacting protein 1) involved in the monoubiquitinated FANCD2-DNA damage repair pathway were significantly associated with breast cancer risk.
Impact of PTEN protein expression on benefit from adjuvant trastuzumab in early-stage human epidermal growth factor receptor 2-positive breast cancer in the North Central Cancer Treatment Group N9831 trial.
It seems that PTEN status determined by protein expression may discriminate between subgroups with poor and good prognosis in premenopausal HR-positive BC patients receiving adjuvant OA.
In this study, the eukaryotic expression vectors pBP-wt-PTEN (containing a wild-type PTEN gene) and pBP-G129R-PTEN (containing a mutant PTEN gene) were used to transfect breast cancer ZR-75-1 cells.
Germline DNA from 1054 BRCA-mutation-negative Hispanic women with hereditary BC (BC diagnosed at age <51 years, bilateral BC, breast and ovarian cancer, or BC diagnosed at ages 51-70 years with ≥2 first-degree or second-degree relatives who had BC diagnosed at age <70 years), 312 local controls, and 887 multiethnic cohort controls was sequenced and analyzed for 12 known and suspected, high-penetrance and moderate-penetrance cancer susceptibility genes (ataxia telangiectasia mutated [ATM], breast cancer 1 interacting protein C-terminal helicase 1 [BRIP1], cadherin 1 [CDH1], checkpoint kinase 2 [CHEK2], nibrin [NBN], neurofibromatosis type 1 [NF1], partner and localizer of BRCA2 [PALB2], phosphatase and tensin homolog [PTEN], RAD51 paralog 3 [RAD51C], RAD51D, serine/threonine kinase 11 [STK11], and TP53).
These findings suggest that MEOX1 is a clinically relevant novel target in BCSCs and mesenchymal-like cancer cells in PTEN-deficient trastuzumab resistant breast cancer and may serve as target for future drug development.
Phosphatidylinositol 3-kinase (PI3K) pathway deregulation (that is PIK3CA mutations and/or phosphatase and tensin homolog (PTEN) loss) has been shown to enhance breast cancer cell survival and confer resistance to chemotherapeutic agents.
Inherited or acquired mutations in specific genes involved in the DNA damage response, for example the breast cancer susceptibility genes 1/2 (BRCA1/2), phosphatase and tensin homolog (PTEN) and P53 are associated with various subtypes of breast cancer.
In PTEN-deficient prostate and breast cancers, CHD1 depletion profoundly and specifically suppressed cell proliferation, cell survival and tumorigenic potential.
PTEN is an ubiquitously expressed tumor suppressor which plays a prominent role in the pathogenesis of many types of sporadic solid tumors, including breast cancer, as well as hematologic malignancies.
The meta-analysis indicated that breast cancers with PTEN loss were significantly associated with the tumor size ≥2 cm group (ORFEM = 1.68, 95%CIFEM [1.34, 2.10]), negative expression of estrogen receptor (ORREM = 1.95, 95%CIREM [1.09, 3.49]), negative expression of progesterone receptor (ORFEM = 1.72, 95%CIFEM [1.43, 2.08]), the advanced stage (ORREM = 1.94, 95%CIREM [1.35, 2.80]), positive axillary lymph node metastasis (ORREM = 1.80, 95%CIREM [1.30, 2.50]), and the local recurrence (ORFEM = 1.70, 95%CIFEM [1.26, 2.28]).
BRCA1 and BRCA2 mutations confer very high risks of breast and ovarian cancer. p53 and PTEN mutations lead to very high breast cancer risks associated with rare cancer syndromes.