Nanoparticle albumin-bound paclitaxel/liposomal-encapsulated doxorubicin in HER2-negative metastatic breast cancer patients.

To investigate the toxicity of nab-paclitaxel (wNP)/nonpegylated liposome-encapsulated doxorubicin (wNPLD) combination in HER2-negative metastatic breast cancer (MBC) patients as first-line treatment. Phase I, single-arm study in metastatic breast cancer patients naive to previous chemotherapy for advanced disease. A 3 + 3 dose-escalation design was used to determine the safety.

Prospective study on nanoparticle albumin-bound paclitaxel in advanced breast cancer: clinical results and biological observations in taxane-pretreated patients.

Background: There is a deep need to improve the care of metastatic breast cancer (MBC) patients, since even today it remains an incurable disease. Taxanes are considered the most effective cytotoxic drugs for the treatment of MBC, both in monotherapy and in combined schedules, but the need for synthetic solvents contributes to the severe toxicities and may have a negative impact on the efficacy. Nanoparticle albumin-bound paclitaxel (Nab-paclitaxel) is a colloidal suspension of paclitaxel and human serum albumin initially developed to avoid the toxicities associated with conventional taxanes.

Metronomic oral vinorelbine in advanced breast cancer and non-small-cell lung cancer: current status and future development.

Metronomic chemotherapy (mCT), a frequent administration of low-dose chemotherapy, allows prolonged treatment duration and minimizes the toxicity of standard-dose chemotherapy. mCT has multiple actions against cancer cells including inhibition of angiogenesis and modulation of the immune system. A number of studies lend support to the clinical efficacy of mCT in advanced breast cancer and non-small-cell lung cancer.

Fluorouracil and dose-dense chemotherapy in adjuvant treatment of patients with early-stage breast cancer: an open-label, 2 × 2 factorial, randomised phase 3 trial.

Background: Whether addition of fluorouracil to epirubicin, cyclophosphamide, and paclitaxel (EC-P) is favourable in adjuvant treatment of patients with node-positive breast cancer is controversial, as is the benefit of increased density of dosing. We aimed to address these questions in terms of improvements in disease-free survival.

Methods: In this 2 × 2 factorial, open-label, phase 3 trial, we enrolled patients aged 18-70 years with operable, node positive, early-stage breast cancer from 81 Italian centres.

Epidermal growth factor receptor gene copy number may predict lapatinib sensitivity in HER2-positive metastatic breast cancer.

Objective: Lapatinib, a dual HER2/EGFR tyrosine kinase inhibitor (TKI), associated to capecitabine represents the treatment of choice in HER2-positive metastatic breast cancer (BC) patients in progression after trastuzumab-based therapy. Though lapatinib-based therapy prolongs the time to progression, its efficacy is often limited by the development of drug resistance. It is aimed to evaluate novel biomarkers predictive of lapatinib response, we analyzed EGFR protein and gene status in a series of 50 metastatic HER2-positive BC patients.

Maintenance bevacizumab beyond first-line paclitaxel plus bevacizumab in patients with Her2-negative hormone receptor-positive metastatic breast cancer: efficacy in combination with hormonal therapy.

Background: Data on efficacy of bevacizumab (B) beyond first-line taxane -including regimen (BT) as first-line treatment are lacking. Although preclinical results that anti-angiogenic agents combined with hormonal therapy (HT) could be active, no clinical data exist about combination of maintenance Bevacizumab (mBev) with HT.

Methods: Thirty-five patients who experienced a response after first-line BT, were given mBev at the dose of 15 mg/kg every 3 weeks.

Magnitude of risks and benefits of the addition of bevacizumab to chemotherapy for advanced breast cancer patients: Meta-regression analysis of randomized trials.

Background: Although the addition of bevacizumab significantly improves the efficacy of chemotherapy for advanced breast cancer, regulatory concerns still exist with regard to the magnitude of the benefits and the overall safety profile.

Methods: A literature-based meta-analysis to quantify the magnitude of benefit and safety of adding bevacizumab to chemotherapy for advanced breast cancer patients was conducted. Meta-regression and sensitivity analyses were also performed to identify additional predictors of outcome and to assess the influence of trial design.

HER2 protein and gene variation between primary and metastatic breast cancer: significance and impact on patient care.

Purpose: To analyze HER2 status in primary breast cancer (PBC) compared with correspondent metachronous metastases and to investigate whether BC phenotype may be predictive of change in HER2 expression.

Experimental Design: HER2 was investigated by immunohistochemistry, silver in situ hybridization (SISH), and FISH, in a series of 137 tumors, building up a tissue microarray to concurrently analyze each single PBC and metastatic (MBC) on the same slide.

Results: HER2 status was discordant in 14 cases (10%): 12 negative in PBC and positive in metastases and two positive in PBC and negative in metastases (P = 0.

Colorectal cancer after breast cancer: a case-control study.

Introduction: The risk of colorectal cancer (CRC) after BC and the additional risk factor of tamoxifen exposure were investigated by several studies with conflicting results. We performed a case-control study aimed at investigating if a past history of breast cancer is a risk factor of developing adenomas or CRC and establishing whether tamoxifen exposure is an additional risk factor.

Materials And Methods: We enrolled 175 asymptomatic women with a past history of BC and invited them to undergo a screening colonoscopy.

Clinical outcome of patients with brain metastases from HER2-positive breast cancer treated with lapatinib and capecitabine.

Background: In the present study, we investigated the clinical outcome of patients with brain metastases (BMs) from human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC) treated with lapatinib and capecitabine (LC).

Methods: Of 81 HER2+ metastatic BC patients treated with LC at two Italian institutions, 30 patients with BMs eligible for the analysis were identified. All patients were pretreated with trastuzumab for metastatic disease.

Time to first tumor progression as outcome predictor of a second trasuzumab-based therapy beyond progression in HER-2 positive metastatic breast cancer.

In a previous analysis performed on a cohort of 37 HER-2 positive metastatic breast cancer (MBC) patients treated with trastuzumab beyond progression, we found that a second trastuzumab-based therapy is associated with a considerable response rate and preserved time to progression as compared with a first trastuzumab-based therapy. In the present study, we extended the analysis to a total of 69 patients treated in four different italian Institutions, also trying to identify clinical predictors of sensitivity to a second trastuzumab-based therapy beyond progression. Efficacy results on the overall population confirmed that a second trastuzumab-based therapy beyond progression is an active regimen (27.

Taxanes and gemcitabine doublets in the management of HER-2 negative metastatic breast cancer: towards optimization of association and schedule.

The management of human epidermal receptor-2 (HER-2) negative metastatic breast cancer (MBC) is usually problematic, since no standard therapy exists in this setting. For some patients, combination chemotherapy represents a valuable approach, although its use is often limited by the risks of increased toxicity as well as impairments in quality of life (QoL) that often outweigh the marginal efficacy benefit. Against this background, the use of taxanes, either paclitaxel or docetaxel, in combination with gemcitabine as first-line treatment of HER-2 negative MBC is supported by the evidence of the single-agent activity of these drugs, beneficial pharmacological interactions, different mechanisms of action and largely non superimposable toxicity profiles.

Do HER-2 positive metastatic breast cancer patients benefit from the use of trastuzumab beyond disease progression? A mono-institutional experience and systematic review of observational studies.

Though preclinical evidence supports the protracted use of trastuzumab to reach sustained anti-tumor activity, the activity of trastuzumab beyond disease progression remains controversial in HER-2 over-expressing (HER-2+) metastatic breast cancer (MBC) patients. We retrospectively evaluated a total of 59 patients with HER-2 + MBC treated at our institution with trastuzumab-based therapies. Our results were added to those obtained in similar observational studies and summary estimates for overall response (OR) and clinical benefit (CB) to first and second trastuzumab-based lines were calculated.

Impact of celecoxib on capecitabine tolerability and activity in pretreated metastatic breast cancer: results of a phase II study with biomarker evaluation.

Background: Preclinical evidence suggests that the cyclo-oxygenase-2 (COX-2) enzyme plays an important role in breast cancer progression. The aim of the present phase II study was to determine the activity and safety of the combination of the COX-2 inhibitor celecoxib with capecitabine in metastatic breast cancer (MBC) patients pretreated with anthracyclines and/or taxanes.

Methods: Eligible patients received capecitabine 1,000 mg/m(2) twice daily on days 1-14 every 21 days and celecoxib 200 mg twice daily, continuously, until disease progression or unacceptable toxicity.

Aromatase inhibitors in post-menopausal metastatic breast carcinoma.

To summarise the advances in the hormonal treatment of post-menopausal metastatic breast cancer, this paper reviews the published literature regarding the randomised trials comparing aromatase inhibitors (AIs) versus tamoxifen as a first-line therapeutic choice, or AIs versus megestrole acetate (MEG) as a second-line option. The pooled analysis of these authors on AI versus MEG as a second-line option for post-menopausal metastatic breast cancer suggested that AIs do not add any significant benefit over MEG in terms of overall response rate (ORR) and time to progression. According to the Cochrane Database, use of an AI as a second-line therapy versus any other endocrine therapy (mostly MEG) has shown a significant benefit in terms of overall survival, but not for progression-free survival, clinical benefit (CB) or ORR.

Clinical evaluation of the use of exemestane as further hormonal therapy after nonsteroidal aromatase inhibitors in postmenopausal metastatic breast cancer patients.

Objectives: The aromatase inhibitors Anastrozole, Letrozole (type 2 nonsteroidal aromatase inhibitors: n-SAI) and Exemestane (type 1 steroidal aromatase inactivator) are used respectively as first- and second-line hormonal therapy in postmenopausal metastatic breast cancer women. Few clinical data are published on the sequential use of different classes of aromatase inhibitors.

Methods: We report an analysis on 30 postmenopausal metastatic breast cancer women treated between January 2000 and May 2002 in 2 Italian Oncology Institutions with the hormonal sequence n-SAI (Anastrozole, Letrozole) --> Exemestane.

HER2/neu role in breast cancer: from a prognostic foe to a predictive friend.

Purpose Of Review: The principal effort of this review was to elucidate the role of human epidermal growth factor receptor 2/neu expression in breast cancer, either as an independent prognostic factor or a predictive marker of response to antineoplastic therapy, in light of the most recent results obtained with the use of trastuzumab, in either the metastatic or the adjuvant setting.

Recent Findings: Human epidermal growth factor receptor 2-overexpressing breast cancer is known to be associated with particularly aggressive disease and poor prognosis. On the other hand, human epidermal growth factor receptor 2/neu overexpression may predict response to endocrine therapy or chemotherapy.

Is recurrent venous thromboembolism after therapy reduced by low-molecular-weight heparin compared with oral anticoagulants?

Purposes: To evaluate whether the incidence of recurrent venous thromboembolism (VTE) events after therapy differs for patients treated with long-term low-molecular-weight heparin (LMWH) or oral anticoagulant therapy (OAT).

Methods: All randomized studies were searched through computerized queries of MEDLINE, the Cochrane Controlled Trials Register, the American Society of Hematology abstract database, and the American Society of Clinical Oncology abstract database.

Results: Eleven studies including 2,907 patients were identified.