Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This tenth article in our series on breast disease focuses on locally advanced breast cancer and inflammatory breast cancer -- both associated with a high risk of subsequent distant metastases.
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PMID:Locally advanced and inflammatory breast cancer. 1633 85

Inflammatory breast cancer is a highly aggressive and metastatic form of locally advanced breast cancer that carries a significantly worse prognosis than non-inflammatory breast cancers. Unfortunately, the molecular basis of this deadly form of breast cancer has been understudied. Over the past 10 years new studies have begun to reveal a unique molecular profile of IBC shedding light on its unique ability to rapidly invade and metastasize via the dermal lymphatic system of the skin overlying the breast. The goal of this review is to introduce IBC to the reader and provide a brief overview of what is known about the metastatic mechanisms of the disease.
Clin Exp Metastasis 2005
PMID:The current understanding of the molecular determinants of inflammatory breast cancer metastasis. 1664 1

Inflammatory breast cancer (IBC), accounting for 1-5% of all breast cancers, is the most aggressive form of breast cancer. Its biologically aggressive nature is identified by the rapid time to progression, its tendency to affect younger women, the high proportion of local and distant metastases present at diagnosis, and lower overall survival despite the use of multimodality therapy. With epidemiologic and molecular evidence now suggesting that IBC may represent a distinct disease entity rather than part of the spectrum of locally advanced breast cancer (LABC), accurate differentiation of these two disease processes has never been more crucial to ensure appropriate treatment. This review addresses the historical milestones and clinical characteristics involved in the differentiation of IBC and briefly discusses the emerging molecular data that may facilitate the distinction of IBC from LABC.
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PMID:Clinical aspects of inflammatory breast cancer. 1673 85

Sentinel lymph node biopsy (SLNB) has become an accepted standard of care to stage the axilla for clinically node-negative early stage breast cancer. In experienced hands, studies have shown an acceptable rate of identification of the sentinel lymph node (SLN) with blue dye only. Lymphazurin is occasionally associated with severe allergic reaction, including anaphylaxis and death. The use of methylene blue alone as a method of identifying the SLN in breast cancer has been reported once previously in the literature. Methylene blue may be an acceptable alternative with fewer deleterious side effects. Medical records of patients, who underwent sentinel node mapping between September 2003 and March 2005 by two surgeons at an academic medical center were reviewed. SLN mapping was performed by periareolar injection of 5 cc of 1% methylene blue. All patients with positive SLNs underwent completion axillary node dissection. During the study period, 141 consecutive patients with clinically node-negative axillas and without evidence of inflammatory breast cancer underwent SLNB with injection of methylene blue only. A SLN was identified in 136 of 141 patients (96.5%). Thirty-three of 136 SLNs (24%) harbored metastatic disease. No cases of anaphylaxis were noted. In experienced hands, methylene blue alone is a highly sensitive method of detecting SLNs. Avoiding the greater frequency of allergic reactions seen with lymphazurin is an important advantage of methylene blue.
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PMID:Can methylene blue only be used in sentinel lymph node biopsy for breast cancer? 1695 60

Neoadjuvant chemotherapy is standard management for women who have locally advanced or inflammatory breast cancer, but can be applied to all women who may require postoperative chemotherapy for early-stage breast cancer. Disease-free survival and overall survival are equivalent between patients treated with neoadjuvant chemotherapy and patients treated with the same regimen postoperatively. Preoperative chemotherapy can offer women less morbid surgical treatment by down-staging both the primary breast tumor and axillary metastases. Finally, response to chemotherapy can inform clinicians of the chemosensitivity of the tumor, and can predict long-term outcome for women who have breast cancer.
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PMID:Neoadjuvant systemic therapy and the surgical management of breast cancer. 1749 34

Lapatinib is a dual (ErbB-1 and ErB-2) receptor tyrosine kinase inhibitor (TKI) that was recently approved by the FDA for the treatment of advanced breast cancer. It shows synergy with trastuzumab, and has demonstrated clinical activity in trastuzumab-resistant tumour. This paper reviews the drug development of lapatinib from preclinical studies to the pivotal Phase III trial and ongoing clinical studies. Areas of interest include the advantages of small molecule TKIs versus antibodies in targeting HER receptors and the efficacy of lapatinib in the treatment of cerebral metastases. The surprisingly high response rate in inflammatory breast cancer raises the possibility of other novel predictive biomarkers. The potential for combination and sequencing with other biological and cytotoxic agents is both exciting and challenging.
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PMID:Lapatinib: a tyrosine kinase inhibitor with a clinical role in breast cancer. 1771 70

Mastitis carcinomatosa (inflammatory carcinoma) is a very rare form of breast cancer, with a rapid progress, generalisation and dissemination into the vital organs, and lethal issue. Inflammatory carcinoma of the breast (ICB) accounts for 1 to 4 per cent of all breast carcinomas. Only 3 to 6 per cent of patients survive for 5 years, and a great number of patients die within 1 to 2 years, with disseminated metastases. Undefined diagnostical criteria of the desease are responsible of undefined therapeutical procedures. There are still contra-many diction which are well documented in the literature. In this paper we tried to give our contribution to the solution of some of these problems. Today it is clear that tumour embolism in dermal lymphatics of the involved breast skin is a pathohistologic basis of this fatal desease. Accordingly consequences are visible in all clinical signs, which have a very poor prognosis. There is a very large group of local advanced breast carcinomas that are similar to the ICB, but that are not really ICB. In fact, although all these malignant deseases are very similar, their differentiation is very important esspecialy because of their evaluation. A great number of other benignant deseases have very similar signs. Therefore ICB is a interdisciplinary problem.
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PMID:[Current diagnosis of classic mastitis carcinomatosa]. 1797

Breast cancer is the most common cancer and the second leading cause of cancer death in American women. It was the second most common cancer in the world in 2002, with more than 1 million new cases. Despite advances in early detection and the understanding of the molecular bases of breast cancer biology, about 30% of patients with early-stage breast cancer have recurrent disease. To offer more effective and less toxic treatment, selecting therapies requires considering the patient and the clinical and molecular characteristics of the tumor. Systemic treatment of breast cancer includes cytotoxic, hormonal, and immunotherapeutic agents. These medications are used in the adjuvant, neoadjuvant, and metastatic settings. In general, systemic agents are active at the beginning of therapy in 90% of primary breast cancers and 50% of metastases. However, after a variable period of time, progression occurs. At that point, resistance to therapy is not only common but expected. Herein we review general mechanisms of drug resistance, including multidrug resistance by P-glycoprotein and the multidrug resistance protein family in association with specific agents and their metabolism, emergence of refractory tumors associated with multiple resistance mechanisms, and resistance factors unique to host-tumor-drug interactions. Important anticancer agents specific to breast cancer are described. Breast cancer is the most common type of cancer and the second leading cause of cancer death in American women. In 2002, 209,995 new cases of breast cancer were registered, and 42,913 patients died of it. In 5 years, the annual prevalence of breast cancer will reach 968,731 cases in the United States. World wide, the problem is just as significant, as breast cancer is the most frequent cancer after nonmelanoma skin cancer, with more than 1 million new cases in 2002 and an expected annual prevalence of more than 4.4 million in 5 years. Breast cancer treatment currently requires the joint efforts of a multidisciplinary team. The alternatives for treatment are constantly expanding. With the use of new effective chemotherapy, hormone therapy, and biological agents and with information regarding more effective ways to integrate systemic therapy, surgery, and radiation therapy, elaborating an appropriate treatment plan is becoming more complex. Developing such a plan should be based on knowledge of the benefits and potential acute and late toxic effects of each of the therapy regimens. Despite advances in early detection and understanding of the molecular bases of breast cancer biology, approximately 30% of all patients with early-stage breast cancer have recurrent disease, which is metastatic in most cases. The rates of local and systemic recurrence vary within different series, but in general, distant recurrences are dominant, strengthening the hypothesis that breast cancer is a systemic disease from presentation. On the other hand, local recurrence may signal a posterior systemic relapse in a considerable number of patients within 2 to 5 years after completion of treatment. To offer better treatment with increased efficacy and low toxicity, selecting therapies based on the patient and the clinical and molecular characteristics of the tumor is necessary. Consideration of these factors should be incorporated in clinical practice after appropriate validation studies are performed to avoid confounding results, making them true prognostic and predictive factors. A prognostic factor is a measurable clinical or biological characteristic associated with a disease-free or overall survival period in the absence of adjuvant therapy, whereas a predictive factor is any measurable characteristic associated with a response or lack of a response to a specific treatment. The main prognostic factors associated with breast cancer are the number of lymph nodes involved, tumor size, histological grade, and hormone receptor status, the first two of which are the basis for the AJCC staging system. The sixth edition of the American Joint Committee on Cancer staging system allows better prediction of prognosis by stage. However, after determining the stage, histological grade, and hormone receptor status, the tumor can behave in an unexpected manner, and the prognosis can vary. Other prognostic and predictive factors have been studied in an effort to explain this phenomenon, some of which are more relevant than others: HER-2/neu gene amplification and protein expression, expression of other members of the epithelial growth factor receptor family, S phase fraction, DNA ploidy, p53 gene mutations, cyclin E, p27 dysregulation, the presence of tumor cells in the circulation or bone marrow, and perineural and lymphovascular space invasion. Systemic treatment of breast cancer includes the use of cytotoxic, hormonal, and immunotherapeutic agents. All of these agents are used in the adjuvant, neoadjuvant, and metastatic setting. Adjuvant systemic therapy is used in patients after they undergo primary surgical resection of their breast tumor and axillary nodes and who have a significant risk of systemic recurrence. Multiple studies have demonstrated that adjuvant therapy for early-stage breast cancer produces a 23% or greater improvement in disease-free survival and a 15% or greater increase in overall survival rates. Recommendations for the use of adjuvant therapy are based on the individual patient's risk and the balance between absolute benefit and toxicity. Anthracycline-based regimens are preferred, and the addition of taxanes increases the survival rate in patients with lymph node-positive disease. Adjuvant hormone therapy accounts for almost two thirds of the benefit of adjuvant therapy overall in patients with hormone-receptor-positive breast cancer. Tamoxifen is considered the standard of care in premenopausal patients. In comparison, the aromatase inhibitor anastrozole has been proven to be superior to tamoxifen in postmenopausal patients with early-stage breast cancer. The adjuvant use of monoclonal antibodies and targeted therapies other than hormone therapy is being studied. Interestingly, some patients have an early recurrence even though they have a tumor with good prognostic features and at a favorable stage. These recurrences have been explained by the existence of certain cellular characteristics at the molecular level that make the tumor cells resistant to therapy. Selection of resistant cell clones of micrometastatic disease has also been proposed as an explanation for these events. Neoadjuvant systemic therapy, which is the standard of care for patients with locally advanced and inflammatory breast cancer, is becoming more popular. It reduces the tumor volume, thus increasing the possibility of breast conservation, and at the same time allows identification of in vivo tumor sensitivity to different agents. The pathological response to neoadj uvant systemic therapy in the breast and lymph nodes correlates with patient survival. Use of this treatment modality produces survival rates identical to those obtained with the standard adjuvant approach. The rates of pathological complete response (pCR) to neoadjuvant systemic therapy vary according to the regimen used, ranging from 6% to 15% with anthracycline-based regimens to almost 30% with the addition of a noncross-resistant agent such as a taxane. In one study, the addition of neoadjuvant trastuzumab in patients with HER-2-positive breast tumors increased the pCR rate to 65%. Primary hormone therapy has also been used in the neoadjuvant systemic setting. Although the pCR rates with this therapy are low, it significantly increases breast conservation. Currently, neoadjuvant systemic therapy is an important tool in not only assessing tumor response to an agent but also studying the mechanisms of action of the agent and its effects at the cellular level. However, no tumor response is observed in some cases despite the use of appropriate therapy. The tumor continues growing during treatment in such cases, a phenomenon called primary resistance to therapy. The use of palliative systemic therapy for metastatic breast cancer is challenging. Five percent of newly diagnosed cases of breast cancer are metastatic, and 30% of treated patients have a systemic recurrence. Once metastatic disease develops, the possibility of a cure is very limited or practically nonexistent. In this heterogeneous group of patients, the 5-year survival rate is 20%, and the median survival duration varies from 12 to 24 months. In this setting, breast cancer has multiple clinical presentations, and the therapy for it should be chosen according to the patient's tumor characteristics, previous treatment, and performance status with the goal of improving survival without compromising quality of life. Treatment resistance is most commonly seen in such patients. They initially may have a response to different agents, but the responses are not sustained, and, in general, the rates of response to subsequent agents are lower. Table 1 summarizes metastatic breast cancer response rates to single-agent systemic therapy.
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PMID:Overview of resistance to systemic therapy in patients with breast cancer. 1799 29

Inflammatory breast cancer (IBC) is an extremely aggressive disease that progresses rapidly and carries a very grim prognosis. It is characterized by erythema, rapid enlargement of the breast, skin ridging, and a characteristic peau d'orange appearance of the skin secondary to dermal lymphatic tumor involvement. Although a palpable tumor may not be present, about 55% to 85% of patients will present with metastases to the axillary or supraclavicular lymph nodes. Diagnosis of IBC is made on the basis of these clinical characteristics, as well as histopathologic verification of carcinoma. Accurate diagnosis is critically important, as multimodal therapy can significantly improve outcomes if instituted early enough.
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PMID:Defining the clinical diagnosis of inflammatory breast cancer. 1830 40

Imaging plays several key roles in the diagnosis and assessment of inflammatory breast cancer (IBC). These include characterization of the known tumor, delineation of locoregional disease in the ipsilateral and contralateral breast and regional lymph node basins, diagnosis of distant metastases, and evaluation of treatment response. We review the role of conventional imaging modalities, including mammography and sonography. We also discuss the potential of using evolving imaging modalities such as magnetic resonance imaging (MRI), positron emission tomography with computed tomography (PET/CT), and more advanced or emerging imaging techniques in the assessment of IBC.
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PMID:Evolving role of imaging modalities in inflammatory breast cancer. 1830 46


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