Induction of ErbB-3 expression by alpha6beta4 integrin contributes to tamoxifen resistance in ERbeta1-negative breast carcinomas.

Background: Tamoxifen is still the most widely used drug in hormone therapy for the treatment of breast cancer. Its benefits in adjuvant treatment are well documented in controlled and randomized clinical studies, which have demonstrated an increase in disease-free intervals of patients with positive hormonal receptors. However, the mechanisms involved in endocrine resistance are not clear.

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.

Fixed dose-rate gemcitabine as radiosensitizer for newly diagnosed glioblastoma: a dose-finding study.

In patients with newly diagnosed glioblastoma multiforme (GBM), concurrent chemo-radiotherapy with temozolomide is the new standard of care. In the present phase I study we investigated the association of gemcitabine, a cell-cycle antimetabolite with radiosensitizing properties, with radiotherapy (RT) in the first line treatment. Gemcitabine was delivered at a fixed dose-rate of 10 mg/m(2)/min weekly for 6 weeks starting 24-72 h prior to, and then concomitantly with RT (2.

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.

Brain radiotherapy during treatment with anticonvulsant therapy as a trigger for toxic epidermal necrolysis.

Toxic epidermal necrolysis (TEN) is a severe mucocutaneous syndrome that can be occasionally caused by anticonvulsant drugs. In some cases, cranial irradiation may act as a precipitating factor. Thus, in cancer patients who suffer from brain metastases and are administered antiepileptic drugs for seizure prophylaxis, the risk of developing TEN after receiving palliative brain radiotherapy cannot be ignored.

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.

Bone and lung metastases from intracranial meningioma.

Fifteen percent of intracranial tumors are represented by meningiomas. Meningioma is usually a benign neoplasm; malignant histology is rare and represents about 2-10% with a 43% incidence of metastasis. The most frequent site of metastasis is the lung and rare are other sites.

Chemotherapy in neoplastic meningitis.

Neoplastic meningitis (NM) is the result of the diffuse or multifocal localization of cancer cells in the cerebral spinal fluid (CSF). NM is more often a late complication of solid tumor or lymphoproliferative malignancies. At present, the goal of therapeutic strategies is palliative and the evaluation of high or low risk is important in identifying which patients could benefit from aggressive treatments such as radiation therapy and chemotherapy.

Early post-operative MRI: correlation with progression-free survival and overall survival time in malignant gliomas.

Forty-seven patients with Glioblastoma (42) and Anaplastic Astrocytoma (5) were studied with MR 24 hrs after surgery. In order to evaluate the role of early MR in defining the extent of surgical resection and its relation with the prognosis of malignant glioma patients, three categories of surgical resection were considered: gross total, sub-total and partial resection. The results were correlated with progression-free survival (PFS) and overall survival (ST).

Major bleedings in the comparisons between low-molecular weight heparin versus oral anticoagulant therapy for venous thromboembolism.

To evaluate the safety (major bleedings) of long-term treatment of symptomatic venous thromboembolism (VTE) using low molecular weight heparin (LMWH) compared with oral anticoagulant therapy (OAT) given for at least 3 months, we analyzed 10 randomized clinical trials enrolling a total of 2817 patients with objectively diagnosed symptomatic deep vein thrombosis, pulmonary embolism or both. The relative risk (RR, incidence of recurrent symptomatic VTE) was combined across the studies, using the inverse variance and the Mantel-Haenszel method. During treatment, major bleeding complications occurred in 2.

Dramatic regression of multiple brain metastases from breast cancer with Capecitabine: another arrow at the bow?

Several chemotherapic agents, which are active against breast cancer, penetrate poorly into the central nervous system. Despite its limited brain penetration, 5-fluorouracil has been a component of effective regimens for brain metastases. Capecitabine is a recently developed oral prodrug that is converted into 5-fluorouracil by sequential enzymatic steps.

Early switch with aromatase inhibitors as adjuvant hormonal therapy for postmenopausal breast cancer: pooled-analysis of 8794 patients.

Background: The magnitude of the survival benefit of aromatase inhibitors (AIs) after 2-3 years of tamoxifen as adjuvant hormonal therapy for early breast cancer is still unclear. We performed a literature-based meta-analysis, to look how much advantages adjuvant the "early switch" strategy add over standard tamoxifen for 5 years.

Methods: A pooled analysis of all phase-III trials was accomplished, and event-based relative risk ratios (RR) with 95% confidence interval (CI) were derived.

Analysis of aneusomy level and HER-2 gene copy number and their effect on amplification rate in breast cancer specimens read as 2+ in immunohistochemical analysis.

Our aim was to determine the aneusomy level and the HER-2 gene copy numbers, by fluorescence in situ hybridization (FISH) and to analyze their impact on the amplification rate in breast carcinomas considered HER-2 weakly positive cases by immunohistochemistry. We evaluated 343 breast carcinomas using double colour FISH (LSI Her-2/neu gene and CEP 17). Monosomy and polysomy were demonstrated in 24.

Second- and third-generation aromatase inhibitors as first-line endocrine therapy in postmenopausal metastatic breast cancer patients: a pooled analysis of the randomised trials.

The purpose of this study was to estimate in all randomised trials the relative risk of overall response rate (ORR), clinical benefit (CB), time to progression (TTP), overall survival (OS), and toxicity of aromatase inhibitors (AI), compared with tamoxifen (Tam) as first-line endocrine therapy in postmenopausal metastatic breast cancer (PMBC) women. Prospective randomised studies were searched through computerised queries of MEDLINE, EMBASE, and the American Society of Clinical Oncology (ASCO) abstract database. Relative risk, 95% confidence interval, and heterogeneity were derived according to the inverse variance and Mantel-Haenszel method and Q statistics.

A phase II study on metastatic breast cancer patients treated with weekly vinorelbine with or without trastuzumab according to HER2 expression: changing the natural history of HER2-positive disease.

Purpose: To observe whether in pretreated metastatic breast cancer patients with HER2-positive disease vinorelbine plus trastuzumab can produce different overall response rate (ORR), time to progression (TTP), and overall survival (OS) from women with HER2-negative tumors treated with vinorelbine alone.

Methods: Between June 2000 and January 2004, 68 consecutive women were enrolled: 33 patients received vinorelbine (V) alone, while 35 patients were given trastuzumab plus vinorelbine (T+V) according to HER2 expression determined by immunohistochemistry. In tumors scored +2, HER2 gene amplification was determined by fluorescence in situ hybridization.