Assessing the long-term prognostic ability of the 70 gene expression signature MammaPrint in an Italian single-center prospective cohort study of early-stage intermediate-risk breast cancer patients.

Purpose: The aim of this study was to assess the prognostic performance of the 70-gene signature, MammaPrint, in an Italian single-center prospective cohort of early-stage intermediate-risk breast cancer (BC) patients.

Methods: A total of 195 eligible early BC cases were tested for genomic risk between 2006 and 2013. In this retrospective analysis, the association of genomic risk with distant metastasis-free survival (DMFS) and overall survival (OS) were assessed using Cox regression models, adjusting for clinical and pathological tumor characteristics.

Prediction of response to neoadjuvant chemotherapy by MammaTyper® across breast cancer subtypes: A retrospective cross-sectional study.

Background: Neoadjuvant chemotherapy (NACT) is widely used in the treatment of triple-negative and HER2-positive breast cancer (BC), but its use in estrogen receptor (ER) and/or progesterone receptor (PR) positive/HER2-negative BC is questioned because of the low pathologic complete response (pCR) rates. This retrospective study assessed the mRNA-based MammaTyper® assay's capability of predicting pCR with NACT, and ER, PR, Ki67, and HER2 status at immunohistochemical (IHC) through transcriptomics.

Methods: Diagnostic biopsies from 76 BC patients treated at the Cremona Hospital between 2012-2018 were analyzed.

Computational reactive-diffusive modeling for stratification and prognosis determination of patients with breast cancer receiving Olaparib.

Mathematical models based on partial differential equations (PDEs) can be exploited to handle clinical data with space/time dimensions, e.g. tumor growth challenged by neoadjuvant therapy.

Clinical, Radiometabolic and Immunologic Effects of Olaparib in Locally Advanced Triple Negative Breast Cancer: The OLTRE Window of Opportunity Trial.

Introduction: Olaparib is effective in metastatic triple negative breast cancer (TNBC) carrying germline mutations in DNA damage repair (DDR) genes (g-mut). The OLTRE window-of-opportunity trial preliminarily investigated potential pathologic, radiometabolic and immune biomarkers of early-response to olaparib in g-wild-type (wt) TNBC and, as proof-of-concept in g-mut HER2-negative BC.

Methods: Patients received olaparib for 3 weeks (3w) before standard neoadjuvant chemotherapy and underwent multiple FDG-PET/CT scan (basal, after olaparib), clinical assessments (basal, every 3w), tumor biopsies and blood samplings (baseline, after olaparib).

Acute Generalized Exanthematous Pustulosis (AGEP) in 12 Patients Treated for SARS-CoV-2 Positive Pneumonia.

The novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is rapidly spreading throughout the world. The study describes 12 patients with SARS-CoV-2 pneumonia, who developed an acute erythematous rash with nonfollicular pinhead-sized pustules, without mucosal involvement. The clinical differential diagnosis was viral rash, acute generalized exanthematous pustulosis (AGEP), or multiform erythema.

Benefit of the addition of hormone therapy to neoadjuvant anthracycline-based chemotherapy for breast cancer: comparison of predicted and observed pCR.

Introduction: Neoadjuvant hormonal therapy is generally considered a valid option for hormone receptor positive breast cancer (BC) patients who are unfit for chemotherapy or surgery.

Aims: Whilst numerous studies analyzed efficacy of neoadjuvant chemotherapy (CT) or endocrine therapy (HT) alone in hormone receptor positive patients, there is a lack of research looking at the usefulness of a preoperative combinatorial approach of CT and HT in this patient subgroup.

Methods: Using a predictive model previously described in the literature, developed to analyze the probability of benefit from preoperative chemotherapy, we were able to compare pathological complete response (pCR) rates expected with the use of CT alone with the pCR rates reported in a population of 192 patients treated with the combination of tamoxifen plus anthracycline-based CT at Cremona Hospital between 2003 and 2006.

Could gonadotropin-releasing hormone analogs be helpful in the treatment of triple-negative breast cancer?

Aim: Treatment of triple-negative breast cancer (TNBC) imposes great challenges, due to a lack of molecular targets. While use of gonadotropin-releasing hormone (GnRH) analogs has been validated in ER-positive breast cancer, this option has not been investigated in TNBC, even though a significant portion of these tumors upregulate GnRH receptors. We performed a meta-analysis of the literature to evaluate the effect of GnRH analogs in TNBC.

Hypoxia-related biological markers as predictors of epirubicin-based treatment responsiveness and resistance in locally advanced breast cancer.

Purpose: To identify hypoxia-related biomarkers indicative of response and resistance to epirubicin treatment in patients with locally advanced breast cancer.

Patients And Methods: One hundred seventy-six women with T2-4 N0-1 breast tumours were randomly assigned to receive epirubicin 120 mg/m2/1-21 (EPI ARM), epirubicin 120 mg/m2/1-21 + erythropoietin 10.000 IU sc three times weekly (EPI-EPO ARM) and epirubicin 40 mg/m2/w-q21 (EPI-W ARM).

A Phase II study of olaparib in breast cancer patients: biological evaluation from a 'window of opportunity' trial.

The OLTRE trial (ClinicalTrials.gov number: NCT02681562) is an open-label, 'window of opportunity' Phase II controlled trial to evaluate the biological activity of olaparib in locally advanced triple-negative breast cancer compared with other subtypes of locally advanced breast cancer patients carrying germinal BRCA mutation receiving olaparib with the same treatment approach. The primary end point is to investigate the correlation between baseline gene and protein expression profile in order to identify possible predictive markers of response to olaparib.

Effect of Primary Letrozole Treatment on Tumor Expression of mTOR and HIF-1α and Relation to Clinical Response.

Introduction: Recently the combination of the mammalian target of rapamycin (mTOR) inhibitor everolimus and the aromatase inhibitor exemestane has been shown to double the progression-free survival rate in advanced breast cancer. However, the effect of the interrelated pathways of hypoxia-inducible factor-1α (HIF-1α) and mTOR signaling, both of which are associated with a more aggressive breast cancer phenotype and endocrine resistance, on response in the neoadjuvant setting is unknown. We, therefore, have investigated the influence of these pathways with the aim of better defining those patients most likely to benefit from an endocrine-based therapy associated with/without mTOR inhibitors.

The prolyl hydroxylase enzymes are positively associated with hypoxia-inducible factor-1α and vascular endothelial growth factor in human breast cancer and alter in response to primary systemic treatment with epirubicin and tamoxifen.

Introduction: The purpose of the present study was to investigate the relationship of expression of hypoxia inducible factor (HIF)-1α-modifying enzymes prolyl hydroxylase (PHD)1, PHD2 and PHD3 to response of tumours and survival in breast cancer patients enrolled in a phase II trial of neoadjuvant anthracycline and tamoxifen therapy.

Methods: The expression of PHD1, PHD2 and PHD3 together with HIF-1α and the HIF-inducible genes vascular endothelial cell growth factor (VEGF) and carbonic anhydrase IX were assessed by immunohistochemistry using a tissue microarray approach in 211 patients with T2-4 N0-1 breast cancer enrolled in a randomised trial comparing single-agent epirubicin versus epirubicin and tamoxifen as the primary systemic treatment.

Results: PHD1, PHD2 and PHD3 were detected in 47/179 (26.

Anti-angiogenic effect of tamoxifen combined with epirubicin in breast cancer patients.

Vascular endothelial growth factor A (VEGF-A) and vascular endothelial growth factor receptor 2 (VEGFR2) are the key factors mediating neo-vascularization. They are often coexpressed in breast cancer. Sex steroids may stimulate angiogenesis via the estrogen receptor (ER) pathway.

Immunomodulation of FOXP3+ regulatory T cells by the aromatase inhibitor letrozole in breast cancer patients.

Purpose: We have shown previously that tumor infiltration by FOXP3+ regulatory T cells (Treg) is associated with increased relapse and shorter survival of patients with both in situ and invasive breast cancer. Because estrogen regulates Treg numbers in mice and promotes the proliferation of human Tregs, we hypothesized that blocking estrogen receptor-alpha signaling would abrogate Tregs and be associated with response to hormonal therapy and increased survival.

Experimental Design: FOXP3+ Tregs were quantified in tumor samples collected at baseline by incisional biopsy and after 6 months at definitive surgery in 83 elderly breast cancer patients (T2-4 N0-1) enrolled in a randomized phase II trial based on 6 months of primary letrozole (2.

Phosphorylated ERalpha, HIF-1alpha, and MAPK signaling as predictors of primary endocrine treatment response and resistance in patients with breast cancer.

Purpose: We aimed to identify signaling pathways involved in the response and resistance to aromatase inhibitor therapy in patients with breast cancer.

Patients And Methods: One hundred fourteen women with T2-4 N0-1, estrogen receptor (ER) alpha-positive tumors were randomly assigned to neoadjuvant letrozole or letrozole plus metronomic cyclophosphamide. Twenty-four tumor proteins involved in apoptosis, cell survival, hypoxia, angiogenesis, growth factor, and hormone signaling were assessed by immunohistochemistry in pretreatment samples (eg, caspase 3, phospho- mammalian target of rapamycin, hypoxia-inducible factor 1alpha [HIF-1alpha], vascular endothelial growth factor, mitogen-activated protein kinase [MAPK], phosphorylated epidermal growth factor receptor, phosphorylated ERalpha [pERalpha]).

Down-regulation of phosphatidylinositol 3'-kinase/AKT/molecular target of rapamycin metabolic pathway by primary letrozole-based therapy in human breast cancer.

Purpose: The phosphatidylinositol 3'-kinase (PI3K)/AKT/molecular target of rapamycin (mTOR) pathway is involved in the development of tumor resistance to endocrine therapy in breast cancer cell lines and represents an attractive target for pharmacologic intervention. However, the effects of endocrine therapy with aromatase inhibitors on in vivo expression of this signaling cascade, and its relation to tumor response and patient outcome, is unknown.

Experimental Design: PI3K, phospho-AKT (pAKT) and phospho-mTOR were assessed by immunohistochemistry on tumor specimens collected at baseline and after 6 months of treatment in 113 elderly breast cancer patients consecutively enrolled in a randomized phase II trial of primary letrozole therapy and letrozole associated with metronomic cyclophosphamide.

Regulation of hepatocyte growth factor activator inhibitor 2 by hypoxia in breast cancer.

Purpose: To examine the in vitro regulation of hepatocyte growth factor activator inhibitor type 2 (HAI-2) in breast cancer cells and the in vivo predictive role for the efficacy of chemoendocrine primary therapy in patients with breast cancer.

Materials And Methods: HAI-2 regulation was studied in a panel of breast cancer cell lines comparing normoxia to hypoxia. The effect of HIF-1alpha RNAi on HAI-2 expression was evaluated in these cells.

Role of carbonic anhydrase IX expression in prediction of the efficacy and outcome of primary epirubicin/tamoxifen therapy for breast cancer.

The purpose of this study is to investigate the role of carbonic anhydrase IX (CAIX) expression in predicting the response to epirubicin and disease-free survival (DFS) in breast cancer patients enrolled in a single institution trial of primary anthracycline and tamoxifen therapy. CAIX expression was assessed in 183 patients with T2-4 N0-1 breast cancer enrolled in a randomized trial comparing four cycles of single agent epirubicin versus epirubicin+tamoxifen as primary systemic treatment. All patients received postoperatively four cycles of the four weekly i.

The circadian rhythm of biochemical markers of bone resorption is normally synchronized in breast cancer patients with bone lytic metastases independently of tumor load.

Background: Bone metastases are devastating events resulting in disruption of local bone remodeling processes. Physiological bone turnover has a circadian rhythm. No data are available on the circadian pattern of bone turnover markers in patients with bone metastases.

Hypoxia-inducible factor-1alpha expression predicts a poor response to primary chemoendocrine therapy and disease-free survival in primary human breast cancer.

Purpose: To investigate the relationship of hypoxia-inducible factor-1alpha (HIF-1alpha) tumor expression in predicting the response to epirubicin and disease-free survival (DFS) in patients with breast cancer enrolled in a single institution trial of primary anthracycline and tamoxifen therapy.

Experimental Design: The expression of HIF-1alpha was assessed by immunohistochemistry in 187 patients with T(2-4) N(0-1) breast cancer enrolled in a randomized trial comparing four cycles of single agent epirubicin versus epirubicin + tamoxifen as primary systemic treatment. All patients postoperatively received four cycles of the four weekly i.

Randomized phase II trial of letrozole and letrozole plus low-dose metronomic oral cyclophosphamide as primary systemic treatment in elderly breast cancer patients.

Purpose: To investigate the activity of letrozole plus/minus oral metronomic cyclophosphamide as primary systemic treatment (PST) in elderly breast cancer patients.

Methods: One hundred fourteen consecutive elderly women with T2-4 N0-1 and estrogen receptor-positive breast cancer were randomly assigned to primary letrozole therapy (2.5 mg daily for 6 months) or a combination of letrozole plus oral cyclophosphamide (50 mg/daily for 6 months) in an open-labeled, randomized phase II trial.

Magnetic resonance imaging in comparison to clinical palpation in assessing the response of breast cancer to epirubicin primary chemotherapy.

Purpose: To investigate whether magnetic resonance imaging (MRI) is superior to clinical palpation in the assessment of response of breast cancer to primary chemotherapy (PC).

Patients And Methods: Seventy-three patients with T2-4, N0, M0 breast cancer were treated with 3-4 cycles of single agent epirubicin before definitive surgery. MRI was performed at baseline condition and at the end of chemotherapy.

Changes in microvessel density as assessed by CD34 antibodies after primary chemotherapy in human breast cancer.

Background: Several papers have shown that quantitationof tumor angiogenesis in primary breast cancer by counting blood vessels gives an independent assessment of prognosis. The impact of chemotherapy +/- endocrine therapy on the extent of angiogenesis is unknown.

Methods: Matched pair histological tumor samples were obtained before and after primary chemotherapy from 120 breast cancer patients recruited in the same institution.