Orlando Silva

Docetaxel, Cisplatin, and Trastuzumab As Primary Systemic Therapy for Human Epidermal Growth Factor Receptor 2–Positive Locally Advanced Breast Cancer

PURPOSE To evaluate the efficacy and safety of docetaxel, cisplatin, and trastuzumab as primary systemic therapy for human epidermal growth factor receptor 2 (HER2) -positive, locally advanced breast cancer (LABC). PATIENTS AND METHODS Forty-eight patients with immunohistochemistry-confirmed HER2-positive LABC or inflammatory breast cancer received 12 weeks of docetaxel, cisplatin, and trastuzumab with filgrastim, followed by surgery, adjuvant doxorubicin and cyclophosphamide, and locoregional radiotherapy with or without tamoxifen. The primary end point was pathologic complete response (pCR) in breast. RESULTS Baseline mean tumor size was 9.2 cm (range, 4 to 32 cm). pCR occurred in breast in 11 patients (23%; 95% CI, 12% to 37%) and breast and axilla in eight patients (17%; 95% CI, 8% to 30%). pCR rates in breast (HER2 positive, seven of 30 patients, 23% v HER2 negative, four of 18 patients, 22%; P > .05) and breast and axilla (four of 30 patients, 13% v four of 18 patients, 22%, respectively; P > .05) were similar regardless of HER2 status by fluorescence in situ hybridization (FISH). At a median follow-up time of 43 months, 4-year progression-free survival (PFS) rate was 81% (95% CI, 64% to 90%); overall survival (OS) rate was 86% (95% CI, 71% to 94%). In patients with pCR in breast and axilla, PFS and OS rates were 100% (95% CI, inestimable). In patients without pCR, PFS rate was 76% (95% CI, 57% to 88%; P = .15, log-rank test), and OS rate was 83% (95% CI, 66% to 92%; P = .21). Survival rates were similar regardless of FISH status. There were only two grade 4 adverse events. CONCLUSION Twelve weeks of docetaxel, cisplatin, and trastuzumab is clinically active and leads to excellent survival in patients with large, HER2-positive tumors.

Characterization of a Recurrent Germ Line Mutation of the E-Cadherin Gene: Implications for Genetic Testing and Clinical Management

Purpose: To identify germ line CDH1 mutations in hereditary diffuse gastric cancer (HDGC) families and develop guidelines for management of at risk individuals. Experimental Design: We ascertained 31 HDGC previously unreported families, including 10 isolated early-onset diffuse gastric cancer (DGC) cases. Screening for CDH1 germ line mutations was done by denaturing high-performance liquid chromatography and automated DNA sequencing. Results: We identified eight inactivating and one missense CDH1 germ line mutation. The missense mutation conferred in vitro loss of protein function. Two families had the previously described 1003C>T nonsense mutation. Haplotype analysis revealed this to be a recurrent and not a founder mutation. Thirty-six percent (5 of 14) of the families with a documented DGC diagnosed before the age of 50 and other cases of gastric cancer carried CDH1 germ line mutations. Two of 10 isolated cases of DGC in individuals ages <35 years harbored CDH1 germ line mutations. One mutation positive family was ascertained through a family history of lobular breast cancer (LBC) and another through an individual with both DGC and LBC. Occult DGC was identified in five of six prophylactic gastrectomies done on asymptomatic, endoscopically negative 1003C>T mutation carriers. Conclusions: In addition to families with a strong history of early-onset DGC, CDH1 mutation screening should be offered to isolated cases of DGC in individuals ages <35 years and for families with multiple cases of LBC, with any history of DGC or unspecified GI malignancies. Prophylactic gastrectomy is potentially a lifesaving procedure and clinical breast screening is recommended for asymptomatic mutation carriers.

Adverse events risk associated with bevacizumab addition to breast cancer chemotherapy: a meta-analysis

BACKGROUND Bevacizumab is a monoclonal antibody against vascular endothelial growth factor with the ability to increase progression-free survival in metastatic breast cancer (MBC). A systematic review and meta-analysis was conducted to determine the risk of the most clinically relevant adverse outcomes associated with the use of bevacizumab in the treatment of breast cancer. PATIENTS AND METHODS We included phase III clinical trials that used bevacizumab alone or in combination with chemotherapy as for MBC or locally recurrent. Statistical analyses were conducted to calculate summary odds ratio (OR) of the eight most relevant adverse outcomes related with bevacizumab. RESULTS Five clinical trials were included in the meta-analysis. Summary odds ratios obtained showed a statistically significant bevacizumab-associated increased risk in four of the adverse outcomes studied: proteinuria (OR = 27.68), hypertension (OR = 12.76), left ventricular dysfunction (LVD) (OR = 2.25), and hemorrhagic events (OR = 4.07). No statistically significant differences were found for gastrointestinal (GI) perforation, vascular events, fatal events, or febrile neutropenia. CONCLUSIONS Bevacizumab did increase the risk of LVD and hemorrhagic events. The addition of bevacizumab to chemotherapy in patients with metastatic breast cancer was not associated with a significant increase in grade ≥ 3 arterial or venous thromboembolic events, GI perforation, or fatal events.BACKGROUND Bevacizumab is a monoclonal antibody against vascular endothelial growth factor with the ability to increase progression-free survival in metastatic breast cancer (MBC). A systematic review and meta-analysis was conducted to determine the risk of the most clinically relevant adverse outcomes associated with the use of bevacizumab in the treatment of breast cancer. PATIENTS AND METHODS We included phase III clinical trials that used bevacizumab alone or in combination with chemotherapy as for MBC or locally recurrent. Statistical analyses were conducted to calculate summary odds ratio (OR) of the eight most relevant adverse outcomes related with bevacizumab. RESULTS Five clinical trials were included in the meta-analysis. Summary odds ratios obtained showed a statistically significant bevacizumab-associated increased risk in four of the adverse outcomes studied: proteinuria (OR = 27.68), hypertension (OR = 12.76), left ventricular dysfunction (LVD) (OR = 2.25), and hemorrhagic events (OR = 4.07). No statistically significant differences were found for gastrointestinal (GI) perforation, vascular events, fatal events, or febrile neutropenia. CONCLUSIONS Bevacizumab did increase the risk of LVD and hemorrhagic events. The addition of bevacizumab to chemotherapy in patients with metastatic breast cancer was not associated with a significant increase in grade ≥3 arterial or venous thromboembolic events, GI perforation, or fatal events.

Progress Against Solid Tumors in Danger: The Metastatic Breast Cancer Example

Javier Cortes, Vall d’Hebron University Hospital; Medica Scientia Innovation Research, Academic Research Organization, Barcelona, Spain Emiliano Calvo, South Texas Accelerated Research Therapeutics—Madrid, Centro Integral Oncologico Clara Campal, Madrid, Spain Antonio Gonzalez-Martin, Centro Oncologico MD Anderson International Espana, Madrid, Spain Shaheenah Dawood, Dubai Hospital, Dubai Health Authority, Dubai, United Arab Emirates Antonio Llombart-Cussac, Arnau de Vilanova Hospital, Valencia; Medica Scientia Innovation Research, Academic Research Organization, Madrid, Spain Leticia De Mattos-Arruda and Patricia Gomez, Vall d’Hebron University Hospital, Barcelona, Spain Orlando Silva, Sylvester Comprehensive Cancer Center, Miami, FL Edith A. Perez, Mayo Clinic Cancer Center, Jacksonville, FL Hope S. Rugo, University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA Ana Lluch, Hospital Clinico, Valencia, Spain Gabriel N. Hortobagyi, The University of Texas MD Anderson Cancer Center, Houston, TX

Prevalence of hepatitis C infection in patients with non-Hodgkin's lymphoma in South Florida and review of the literature

The etiology of non-Hodgkins lymphoma is unknown in the majority of the cases. Although Epstein - Barr virus, human T-cell leukemia-lymphoma virus and human herpes virus-8 have been established as casual agents in the pathogenesis of specific types of lymphoma, the role of hepatitis C virus (HCV) in lymphomagenesis remains controversial, with marked geographic variability. We conducted an epidemiologic study to evaluate the prevalence of hepatitis C virus infection in patients with lymphoma in South Florida. Ninety consecutive patients with lymphoma and 96 consecutive control patients with solid tumors were tested for HCV. HCV infection was detected in 2 patients with NHL (2.2%) and in 4 control patients (4.1%). Our study does not support the association between HCV and lymphoma in South Florida, US.

Small-cell cancer of the breast: what is the optimal treatment? A report and review of outcomes.

Introduction Primary small-cell cancer of the breast, also known as oat cell carcinoma or neuroendocrine carcinoma of the breast, is a rare disorder with only a few cases reported in the literature since its first description by Wade et al in 1983. Little is known on the optimal treatment and outcomes and a wide variety of treatments, including surgery, chemotherapy, and radiation have been used with different outcomes.

Sunitinib-induced microangiopathic hemolytic anemia with fatal outcome.

Sunitinib, a new vascular endothelial growth factor receptor inhibitor, has demonstrated activity in renal cell carcinoma and is now widely used in the palliative treatment of patients with metastatic renal cell carcinoma. It is generally well tolerated but has been associated with a low incidence of grade 3 and 4 toxicities including fatigue, diarrhea, anorexia, mucositis, skin toxicity, immune thrombocytopenic purpura, hypertension, hypothyroidism, cytopenias, and decreased cardiac ejection fraction. Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) is a rare condition that is severe and may be fatal. Several medications have been implicated in causing TTP-HUS including clopidogrel, mitomycin C, cisplatin. In this report, we describe a case of atypical HUS-microangiopathic hemolytic anemia during treatment with sunitinib in a patient with metastatic renal cell carcinoma. To our knowledge, this is the fourth case of microangiopathic hemolytic anemia associated with sunitinib described in the literature and the first case with fatal outcome despite treatment with plasmapheresis, dialysis, and withdrawal of sunitinib.

A phase II trial of split, low-dose docetaxel and low-dose capecitabine: A tolerable and efficacious regimen in the first-line treatment of patients with HER2/neu-negative metastatic breast cancer

BACKGROUND Successful therapeutic regimens in metastatic breast cancer (MBC) must balance efficacy and tolerability. Docetaxel/capecitabine is an active and commonly used doublet in this setting. Docetaxel upregulates thymidine phosphorylase and thus potentiates the antitumor effects of capecitabine. A schedule with split, low-dose docetaxel in combination with low-dose capecitabine could improve the therapeutic index of this regimen without compromising its clinical activity. PATIENTS AND METHODS Patients with previously untreated HER2/neu-negative MBC were eligible. Treatment consisted of docetaxel 25 mg/m2 on days 1 and 8 in combination with capecitabine 750 mg/m2 twice daily on days 1-14 of a 3-week cycle. Thirty-nine women were enrolled. Median age was 55 years (range, 36-75 years). Fourteen patients had triple-negative disease. Sites of metastasis were as follows: bone (n = 27); liver (n = 15); lung (n = 17); nonregional chest (n = 4); lymph nodes (n = 2); and skin (n = 1). Six patients had bone-only disease. All subjects had a performance status of 0/1. A total of 329 cycles were administered (median, 6; range, 1-50). RESULTS Of 37 patients who received study treatment, 32 had evaluable disease, 1 had a complete response, and 15 had a partial response (overall response rate was 50% in evaluable patients and 43% in the intent-to-treat analysis). Six patients had stable disease. The overall clinical benefit rate was 69% for patients with evaluable disease and 60% overall. Fifteen patients had disease that progressed or had been withdrawn from study at the time of first evaluation. With a median follow-up of 25 months, median time to treatment failure was 4.25 months (95% CI, 1.5-7 months), and median overall survival has not yet been reached. Toxicity was moderate: 15 patients (41%) had grade 3/4 adverse events. CONCLUSION Split, low-dose docetaxel and low-dose capecitabine is an active combination in the first-line treatment of patients with MBC. Toxicity with this schedule was manageable, making it an attractive regimen for further study in combination with targeted agents.

Advanced extramammary Paget's disease of the groin, penis, and scrotum

Extramammary Pagets disease (EMPD) is a rare intraepithelial malignancy arising in areas rich in apocrine glands, such as the perineum, vulva, axilla, scrotum, and penis. We describe the case of a man in his 50s who initially presented with a small eczematous lesion on his right groin, treated with topical ointments for eczema, until excisional biopsy of lesion unequivocally revealed invasive EMPD. Despite aggressive surgical interventions, his disease progressed to involve the scrotum and penis. Deemed unresectable, the patient was treated with systemic chemotherapy with minimal response. The rarity of EMPD, especially of the penis and scrotum, warrants an educated eye and heightened index of suspicion when dealing with eczematous lesions in the groin in any person. Early biopsy and histological examination is crucial for early surgical intervention of the lesions. There are no guidelines available to treat locally advanced unresectable disease. In addition, further studies are needed to identify genetic defects underlying the pathogenesis of this rare disease, to help improve treatment strategies and decrease morbidity.

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