Clinical Implications of Transcriptomic Changes After Neoadjuvant Chemotherapy in Patients with Triple-Negative Breast Cancer.

Background: Pathological response to neoadjuvant chemotherapy (NAC) is critical in prognosis and selection of systemic treatments for patients with triple-negative breast cancer (TNBC). The aim of this study is to identify gene expression-based markers to predict response to NAC.

Patients And Methods: A survey of 43 publicly available gene expression datasets was performed.

DNA methylation and upregulation of ΔNp73 are associated with an adverse prognosis in breast cancer.

Aim: Accumulated evidence suggests that aberrant methylation of the gene and increased levels of ΔNp73 in primary tumours correlate with poor prognosis. However, little is known regarding the transcriptional and functional regulation of the gene in breast cancer. The aim of the present study was to determine the expression of the ΔNp73 isoform, its relationship with DNA methylation of and their clinical prognostic significance in breast cancer patients.

HER2 and β-catenin protein location: importance in the prognosis of breast cancer patients and their correlation when breast cancer cells suffer stressful situations.

In human breast cancer, β-catenin localization has been related with disease prognosis. Since HER2-positive patients are an important subgroup, and that in breast cancer cells a direct interaction of β-catenin/HER2 has been reported, in the present study we have explored whether β-catenin location is related with the disease survival. The study was performed in a tumor bank from patients (n = 140) that did not receive specific anti-HER2 therapy.

Prognostic implication of HSPA (HSP70) in breast cancer patients treated with neoadjuvant anthracycline-based chemotherapy.

Neoadjuvant chemotherapy is used in patients with locally advanced breast cancer to reduce tumor size before surgery. Unfortunately, resistance to chemotherapy may arise from a variety of mechanisms. Heat shock proteins (HSPs), which are highly expressed in mammary tumor cells, have been implicated in anticancer drug resistance.

In MMTV-Her-2/neu transgenic mammary tumors the absence of caveolin-1-/- alters PTEN and NHERF1 but not β-catenin expression.

In a recent study, we have shown that in mammary tumors from mice lacking the Cav-1 gene, there are alterations in specific heat shock proteins as well as in tumor development. With this in mind, we have now investigated other proteins in the same mammary mouse tumor model (Her-2/neu expressing mammary tumors from Cav-1 wild type and Cav-1 null mice), to further comprehend the complex tumor-stroma mechanisms involved in regulating stress responses during tumor development. In this tumor model the cancer cells always lacked of Cav-1, so the KO influenced the Cav-1 in the stroma.

DNA methylation index and methylation profile of invasive ductal breast tumors.

Breast carcinogenesis is a multistep process that involves both genetic and epigenetic alterations. Identification of aberrantly methylated genes in breast tumors and their relation to clinical parameters can contribute to improved diagnostic, prognostic, and therapeutic decision making. Our objective in the present study was to identify the methylation status of 34 cancer-involved genes in invasive ductal carcinomas (IDC).

Aberrant DNA methylation of cancer-related genes in giant breast fibroadenoma: a case report.

Introduction: Giant fibroadenoma is an uncommon variant of benign breast lesions. Aberrant methylation of CpG islands in promoter regions is known to be involved in the silencing of genes (for example, tumor-suppressor genes) and appears to be an early event in the etiology of breast carcinogenesis. Only hypermethylation of p16INK4a has been reported in non-giant breast fibroadenoma.

Simultaneous analysis of the methylation profile of 26 cancer related regions in invasive breast carcinomas by MS-MLPA and drMS-MLPA.

Genetic and epigenetic events play a critical role in the tumorigenic process of breast cancer. The more genes are studied, the more accurate the epigenetic "signature" can be established. The aim of our work has been to apply the technique Methylation-Specific Multiplex Ligation dependent Probe Amplification (MS-MLPA) to study the methylation profile of 26 cancer related gene regions in breast cancers.

Stromal cell expression of caveolin-1 predicts outcome in breast cancer.

Caveolin-1 has been linked to tumor progression and clinical outcome in breast cancer, but a clear resolution of its role as a prognostic marker is lacking. We assessed caveolin-1 levels in normal breast tissue and two breast cancer cohorts for which outcome data were available. We found that caveolin-1 was not expressed in normal breast luminal epithelium but was present in the epithelial compartment of some tumors.

Prognostic value of Bcl-2 in breast cancer patients treated with neoadjuvant anthracycline based chemotherapy.

We have analyzed the predictive/prognostic value of Bcl-2 protein in breast cancer patients treated with neoadjuvant chemotherapy. One hundred and ten patients were submitted to two different chemotherapeutic regimens: a) 5-fluorouracil, adriamycin or epirubicin, and cyclophosphamide (FAC/FEC) during 2-6 cycles before surgery and 3 or 4 additional cycles of FAC/FEC after surgery (n=40) and b) doxorubicin (D) 75 mg/m(2) or epirubicin (E) 120 mg/m(2) during 4 cycles before surgery, and 6 cycles of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) after surgery (n=70). Bcl-2 expression, evaluated by immunohistochemistry, did not change significantly after chemotherapy and was not related to clinical/pathological response.

P-cadherin and beta-catenin are useful prognostic markers in breast cancer patients; beta-catenin interacts with heat shock protein Hsp27.

The cadherin-catenin proteins have in common with heat shock proteins (HSP) the capacity to bind/interact proteins of other classes. Moreover, there are common molecular pathways that connect the HSP response and the cadherin-catenin protein system. In the present study, we have explored whether in breast cancer the HSP might interact functionally with the cadherin-catenin cell adhesion system.

Co-expression of steroid receptors (estrogen receptor alpha and/or progesterone receptors) and Her-2/neu: Clinical implications.

The response of breast cancer patients to endocrine therapy is guided by the expression of two steroid hormone receptors (HR): estrogen receptor alpha (ERalpha) and/or progesterone receptors (PR). In most laboratories the expression of these predictive markers is studied by immunohistochemistry (IHC) in the breast cancer biopsy samples. Another molecular marker that is being increasingly examined in breast cancer is the oncoprotein Her-2/neu, whose expression/amplification predicts the response to anti-Her-2/neu immunotherapy.

Co-expression of steroid hormone receptors (estrogen receptor alpha and/or progesterone receptors) and Her2/neu (c-erbB-2) in breast cancer: clinical outcome following tamoxifen-based adjuvant therapy.

In breast cancer patients, the expression of steroid hormone receptors (HR:ERalpha/PR) appears inversely correlated with Her2/neu (not all reports agree on this negative correlation). Moreover, some but not all studies suggest that HR+/Her2/neu+ patients have a poor response to endocrine therapy, making this special group a matter of debate. In this prospective study we have analyzed the clinical outcome of our HR+/Her2/neu+ patients (n=51) selected from 516 consecutive stages I-II cases, with a follow-up 5-10 years (mean 7.