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  • 机译 保持开放的胸怀:乳腺癌干细胞理论的亮点和争议
    摘要:The discovery that breast cancers contain stem-like cells has fuelled exciting research in the last few years. These cells are referred to as breast cancer stem cells (BCSCs) and are thought to be involved in tumor initiation, progression, and metastasis. Being intrinsically resistant to chemo- and radiotherapy, they are also considered responsible for recurrence of the disease after treatment. BCSCs have been suggested to be at the basis of tumor complexity, as they have the ability to self-renew and give rise to highly proliferating and terminally differentiated cancer cells that comprise the heterogeneous bulk of the tumor. There has been much speculation on the BCSC model, and in this review we address some fundamental questions, such as the identity of BCSCs and their involvement in tumor intra- and interheterogeneity. As an alternative to the BCSC model, we discuss clonal evolution, as both theories show extensive evidence in support of their arguments. Finally, we discuss a unifying idea that reconciles both models, which is based on stem cell plasticity and epigenetic modifications induced by the tumor microenvironment. The implications of cancer stem cell plasticity for drug discovery and future therapeutic interventions are presented.
  • 机译 乳腺癌的休眠
    摘要:Tumor dormancy describes a prolonged quiescent state in which tumor cells are present, but disease progression is not yet clinically apparent. Breast cancer is especially known for long asymptomatic periods, up to 25 years, with no evidence of the disease, followed by a relapse. Factors that determine the cell’s decision to enter a dormant state and that control its duration remain unclear. In recent years, considerable progress has been made in understanding how tumor cells circulating in the blood interact and extravasate into secondary sites and which factors might determine whether these cells survive, remain dormant, or become macrometastases. The mechanisms of tumor cell dormancy are still not clear. Two different hypotheses are currently discussed: tumor cells persist either by completely withdrawing from the cell cycle or by continuing to proliferate at a slow rate that is counterbalanced by cell death. Because dormant disseminated tumor cells may be the founders of metastasis, one hypothesis is that dormant tumor cells, or at least a fraction of them, share stem cell-like characteristics that may be responsible for their long half-lives and their suggested resistance to standard chemotherapy. Therefore, knowledge of the biology of tumor cell dormancy may be the basis from which to develop innovative targeted therapies to control or eliminate this tumor cell fraction. In this review, we discuss biological mechanisms and clinical implications of tumor dormancy in breast cancer patients.
  • 机译 更正
    • 作者:
    • 刊名:Breast Cancer : Targets and Therapy
    • 2012年第期
    摘要:
  • 机译 缩回
    • 作者:
    • 刊名:Breast Cancer : Targets and Therapy
    • 2012年第期
    摘要:
  • 机译 Veritas®在乳房重建中是否起作用?病例报告
    摘要:To reduce operative times and surgical complications in implant-based breast reconstruction, many authors advocate the use of exogenous material (modified xenograft) to support tissue regeneration. In this article, a case is presented in which a bovine collagen patch (Veritas® Collagen Matrix; Synovis Surgical Innovations, St Paul, MN) was used in the immediate breast reconstruction with an implant. The good results obtained in this case confirm Veritas® as a viable alternative to AlloDerm® Regenerative Tissue Matrix (LifeCell Corporation, Branchburg, NJ) and further support its ability to sustain and stimulate recovery of the surrounding tissues.
  • 机译 内皮抑素的体外人类皮肤渗透:潜在的局部经皮治疗对乳腺癌的一级预防和原位癌
    摘要:PurposeOral tamoxifen, a triphenylethylene (TPE), is useful for breast cancer prevention, but its adverse effects limit acceptance by women. Tamoxifen efficacy is related to its major metabolites 4-hydroxytamoxifen (4-OHT) and N-desmethyl-4-hydroxytamoxifen (endoxifen [ENX]). Transdermal delivery of these to the breast may avert the toxicity of oral tamoxifen while maintaining efficacy. We evaluated the relative effciency of skin permeation of 4-OHT and ENX in vitro, and tested oleic acid (OA) as a permeation-enhancer.
  • 机译 阿根廷妇女的浸润性乳腺癌:风险和预后因素与肽抗原和碳水化合物性质的关联
    摘要:ObjectiveIn breast cancer, several tumor markers have been identified. The marker most extensively associated with breast cancer is MUC1. The objective of the study was to analyze prognostic and risk factors in relation to tumor markers in order to clarify breast cancer biology. A total of 349 primary tumor samples and lymph nodes from breast cancer patients were studied. Risk and prognostic factors were considered. An immunohistochemical approach was applied and an extensive statistical analysis was performed, including frequency analysis and analysis of variance. Correlation among variables was performed with principal component analysis.
  • 机译 骨骼,乳房和双膦酸盐:在晚期和早期乳腺癌中使用唑来膦酸的理由
    • 作者:Allan Lipton
    • 刊名:Breast Cancer : Targets and Therapy
    • 2011年第期
    摘要:Bisphosphonates inhibit osteoclast-mediated bone resorption, thereby inhibiting the release of growth factors necessary to promote cancer cell growth, differentiation, and tumor formation in bone. These agents have demonstrated efficacy for delaying the onset and reducing the incidence of skeletal-related events in the advanced breast cancer setting, and have been shown to prevent cancer therapy-induced bone loss in the early breast cancer setting. Emerging clinical data indicate that the role of bisphosphonates in advanced and early breast cancer is evolving. Retrospective analyses and recent clinical trial data show that zoledronic acid may improve outcomes in some patients with breast cancer. Data from ABCSG-12 and ZO-FAST suggest that zoledronic acid may improve disease-free survival in the adjuvant breast cancer setting in postmenopausal women or women with endocrine therapy-induced menopause, and recent data from a predefined subset of the AZURE trial added to the anticancer story. However, the overall negative AZURE trial also raises questions about the role of bisphosphonates as an anticancer agent in patients with breast cancer. Overall, these data suggest that the addition of zoledronic acid to established anticancer regimens may have potential anticancer benefits in specific patient populations, although more studies are required to define its role.
  • 机译 乳腺癌患者骨转移的最佳管理
    • 作者:MH WongN Pavlakis
    • 刊名:Breast Cancer : Targets and Therapy
    • 2011年第期
    摘要:Bone metastasis in breast cancer is a significant clinical problem. It not only indicates incurable disease with a guarded prognosis, but is also associated with skeletal-related morbidities including bone pain, pathological fractures, spinal cord compression, and hypercalcemia. In recent years, the mechanism of bone metastasis has been further elucidated. Bone metastasis involves a vicious cycle of close interaction between the tumor and the bone microenvironment. In patients with bone metastases, the goal of management is to prevent further skeletal-related events, manage complications, reduce bone pain, and improve quality of life. Bisphosphonates are a proven therapy for the above indications. Recently, a drug of a different class, the RANK ligand antibody, denosumab, has been shown to reduce skeletal-related events more than the bisphosphonate, zoledronic acid. Other strategies of clinical value may include surgery, radiotherapy, radiopharmaceuticals, and, of course, effective systemic therapy. In early breast cancer, bisphosphonates may have an antitumor effect and prevent both bone and non-bone metastases. Whilst two important Phase III trials with conflicting results have led to controversy in this topic, final results from these and other key Phase III trials must still be awaited before a firm conclusion can be drawn about the use of bisphosphonates in this setting. Advances in bone markers, predictive biomarkers, multi-imaging modalities, and the introduction of novel agents have ushered in a new era of proactive management for bone metastases in breast cancer.
  • 机译 脑转移在乳腺癌患者预后中的新兴作用
    摘要:Cancer starts with one rogue cell. Through mutations and genomic alterations, the cell acquires specific and stem cell-like characteristics necessary for invasion of a distant organ and ultimately metastasis. Metastatic brain cancer is a particularly formidable disease because of its poor prognosis and the highly resistant nature of the tumor to chemotherapy. Although several types of primary tumors have a tendency to metastasize to the brain, the incidence of brain metastases has increased dramatically in some subsets of breast cancer patients. Several conventional treatments are available, but success is limited and often short-lived. Given that no standard treatment options exist, there is a significant need to investigate the biology of these clinically recalcitrant tumors.
  • 机译 乳房再造:当前和未来的选择
    摘要:When initiated by the devastating diagnosis of cancer, post ablative breast restoration has at its core the goal of restoring anatomic normalcy. The concepts of body image, wholeness, and overall well-being have been introduced to explain the paramount psychological influence the breast has on both individuals and society as a whole. Hence, a growing subspecialty has been established to recreate or simulate the lost breast. At least one third of breast cancer victims consider breast reconstruction. Breast reconstruction post mastectomy may be offered at the time of mastectomy or delayed post mastectomy after adjuvant therapy. This may be utilizing autologous tissues or implants and each has risks and benefits, especially when considering adjuvant therapy. In addition, there has been a move away from a traditional mastectomy to less invasive, but still curative procedures, such as skin-sparing and nipple-sparing mastectomy. These procedures provide the breast envelope to facilitate reconstruction. This paper reviews the primary issues in breast reconstruction, as well as their psychologic, oncologic, and social impact.
  • 机译 依立布林(Halaven):一种针对转移性乳腺癌严重治疗的女性的新型有效治疗方法
    • 作者:J MenisC Twelves
    • 刊名:Breast Cancer : Targets and Therapy
    • 2011年第期
    摘要:Although metastatic breast cancer remains essentially incurable, many patients previously treated with an anthracycline, taxane, and capecitabine are relatively fit and keen to receive further therapy. Several drugs are used in this setting, but with little evidence of clinically relevant benefit, and none have previously shown improved survival. Eribulin (Halaven®) is a nontaxane tubulin-binding agent with a novel mode of action, and was recently approved by the European Medicines Agency and US Food and Drug Agency as a single agent for patients with heavily pretreated metastatic breast cancer. This review provides an overview of the discovery, and preclinical and clinical development of eribulin, culminating in the recently published EMBRACE metastatic breast cancer study.
  • 机译 芳香化酶抑制剂治疗绝经后女性乳腺癌的最新进展
    摘要:Estrogen and its metabolites play a significant role in the proliferation of hormone receptor-positive breast cancer. In postmenopausal women, aromatase inhibitors can significantly reduce estrogen levels by blocking enzyme-mediated estrogen synthesis within tissues. Third-generation aromatase inhibitors have now surpassed tamoxifen as first-line therapy for postmenopausal women with metastatic, hormone receptor-positive, breast cancer, showing improved response rates and time to progression. Aromatase inhibitors have shown incremental improvements in disease-free survival, lower local recurrence rates, lower metastatic recurrence rates, and a lower incidence of contralateral breast cancer over tamoxifen when used in the adjuvant setting. Aromatase inhibitors are recommended to be used as adjuvant therapy within the first 5 years of hormonal therapy and may be used either upfront for 5 years or sequenced with tamoxifen. No superiority of one aromatase inhibitor over another has yet been shown. The side effect profiles of aromatase inhibitors have some key differences compared with tamoxifen. These differences may influence treatment choices as well as impact compliance.
  • 机译 雷洛昔芬的最新进展:在降低绝经后妇女浸润性乳腺癌风险中的作用
    • 作者:Victor G Vogel
    • 刊名:Breast Cancer : Targets and Therapy
    • 2011年第期
    摘要:Risk factors allow us to define women who are at increased lifetime risk for breast cancer, and the most important factor is age. Benign breast disease increases risk, and the most important histologies are atypical lobular or ductal hyperplasia and lobular carcinoma in situ. Family history of breast cancer among first-degree relatives (mother, sisters, daughters) also increases risk. Quantitative measures of risk give accurate predictions of breast cancer incidence for groups of women but not for individual subjects. Multiple published, randomized controlled trials, which employed selective estrogen receptor (ER) modulators (SERMs), have demonstrated consistent reductions of 35% or greater in the risk of ER-positive invasive and noninvasive breast cancer in postmenopausal women. Professional organizations in the US now recommend the use of SERMs to reduce the risk of breast cancer in high-risk, postmenopausal women. Raloxifene and tamoxifen reduce the risk of ER-positive invasive breast cancer with equal efficacy, but raloxifene is associated with a lower risk of thromboembolic disease, benign uterine conditions, and cataracts than tamoxifen in postmenopausal women. No evidence exists establishing whether a reduction in breast cancer risk from either agent translates into reduced breast cancer mortality. Overall quality of life is similar with raloxifene or tamoxifen, but the incidence of dyspareunia, weight gain, and musculoskeletal complaints is higher with raloxifene use, whereas vasomotor symptoms, bladder incontinence, gynecologic symptoms, and leg cramps were higher with tamoxifen use.
  • 机译 拉帕替尼和来曲唑联合治疗激素受体阳性和HER2阳性晚期乳腺癌的临床应用
    摘要:Breast cancers that overexpress human epidermal growth factor receptor-2 (HER2-positive [HER2+]) tend to be biologically aggressive and associated with a poor prognosis, even those that coexpress receptors for estrogen and/or progesterone (hormone receptor-positive [HR+]). Optimal therapy for patients with “double-positive” (HR+/HER2+) breast cancers is still being defined. In this subset of patients, the efficacy of targeted endocrine therapies appears to be diminished by cross-activation or “crosstalk” between estrogen receptor-mediated gene transcription and pathways activated by other growth factor receptors, including HER2. Lapatinib is a tyrosine kinase inhibitor which binds reversibly to the intracellular domains of the epidermal growth factor receptor and HER2, interfering with their ability to initiate signal transduction cascades that promote cancer cell proliferation, survival, and metastasis. In a recently published randomized, placebo-controlled Phase III study in postmenopausal HR+ metastatic breast cancer, the addition of lapatinib to the aromatase inhibitor letrozole significantly improved progression-free survival solely in women who were also HER2+. This article reviews the biology of “double-positive” breast cancers and the rationale underlying combining endocrine and HER2-targeted therapies, including the lapatinib/letrozole combination, for these tumors. Results from the Phase III trial are examined, as well as available data on other combinations of HR and HER2-targeted therapies. Ongoing trials and potential future applications of these combinations in both HR+/HER2+ and other subgroups of breast cancer patients are also discussed.
  • 机译 乳腺癌患者化疗引起的恶心和呕吐的止吐疗法选择
    摘要:Chemotherapy-induced nausea and vomiting (CINV) continues to be one of the most distressing side effects of chemotherapy in breast cancer patients, which can result in poor compliance to therapy that may, in turn, affect overall survival. The extent of CINV is dependent on the emetogenic potential of the individual cytotoxic agents or regimens employed as well as certain patient factors. Advances in our understanding in the pathophysiology of CINV and the identification of risk factors have enabled the utilization of appropriate antiemetic regimens to improve the control of CINV. Most of the chemotherapy regimens used in this patient population are considered to be moderately emetogenic; 60%–90% of chemotherapeutic regimens used in breast cancer patients cause nausea and vomiting, amongst which regimens doxorubicin-cyclophosphamide (AC) combination is commonly regarded as of relatively higher emetogenicity. Currently, corticosteroids, 5-hydroxytryptamine 3 (5-HT3) receptor antagonists, and neurokinin 1 (NK-1) receptor antagonists are the three classes of antiemetic agents with the highest therapeutic index, which have been supported by data from large-scale randomized clinical trials. Treatment guidelines enable physicians to integrate the latest research data into their clinical practices. This review focuses on the three classes of antiemetic therapy options for CINV in breast cancer patients, as well as their safety and tolerability profiles. Recommendations from major guidelines/consensus including from the Multinational Association for Supportive Care in Cancer/European Society of Medical Oncology (MASCC/ESMO), the American Society of Clinical Oncology (ASCO), and the US National Comprehensive Cancer Network (NCCN), are also discussed. With the correct use of antiemetic regimens, chemotherapy-induced vomiting could be prevented in the majority of patients. However, chemotherapy-induced nausea remains an important symptom and a challenge for physicians to manage.
  • 机译 乳腺癌干细胞未来治疗方法开发中的挑战
    摘要:The recurrence of tumors after years of disease-free survival has spurred interest in the concept that cancers may have a stem cell basis. Current speculation holds that as few as 0.1% of the tumor mass may be chemoresistant and radioresistant, harboring stem-like properties that drive tumor survival, development, and metastasis. There are intense investigations to characterize cancer stem cells on the basis of self-renewal and multi-lineage differentiation. Thus far, no successful targeted therapies have been developed and reached the clinic, but as these cells are isolated and characterized, insights may be unraveled. In this review, we discuss the controversy over the origins of the cancer stem cell hypothesis and the unforeseen factors that may facilitate breast cancer stem cell survival and metastasis. We discuss the role of tumor microenvironment, including carcinoma-associated fibroblasts, epigenetic factors, and the Th1/Th2 balance, in supporting breast cancer stem cells. In addition, we have incorporated ideas on the epithelial-to-mesenchymal transition in metastatic dissemination of epithelial malignancies. This area is relevant since breast cancer stem cells have been suggested to revert to a mesenchymal phenotype during the progression of cancer. Finally we discuss prospects of developing targeted therapy including novel treatment modalities such as oncolytic viral therapy, differentiation therapy, and nanotechnology
  • 机译 伊沙贝比隆单药治疗或联合治疗晚期乳腺癌
    摘要:Advanced breast cancer represents a therapeutic challenge for oncologists. Chemotherapy with anthracyclines and taxanes has improved survival in this setting, but resistant and refractory disease is common. Ixabepilone, an epothilone, is a recently approved chemotherapeutic agent, both as a single agent and in combination with capecitabine, with efficacy in patients with resistant advanced disease. In this review, the distinctive properties of this drug are discussed, as well as the clinical evidence of efficacy. Ongoing clinical trials are exploring the role of ixabepilone in several clinical settings: neoadjuvant, adjuvant, and novel combinations.
  • 机译 乳腺癌治疗疫苗的开发进展
    摘要:Various human malignancies are immunogenic and recent cancer vaccine trials have demonstrated potential survival benefit. Breast cancer is immunogenic and there are several tumor associated antigens for which breast cancer vaccines have been developed. Breast cancer vaccines are designed to stimulate the immune response at various steps in the native antigen processing pathway for immunosurveillance. Human epidermal growth factor receptor 2 (HER-2/neu), mucin 1 (MUC-1), and human telomerase reverse transcriptase (hTERT) are some of the most studied antigens actively being targeted for vaccination in breast cancer patients. These vaccines are designed to elicit cytotoxic and/or helper T cell responses. Over the last several years, there has been reported progress in human clinical trials for these antigens. Cancer vaccines have repeatedly been shown to be safe with production of minimal toxicity. Recent clinical advances in the development of cancer vaccines demonstrate the potential clinical benefit that cancer vaccines hold.
  • 机译 贝伐单抗在晚期转移性乳腺癌治疗中作用的证据:综述
    摘要:Angiogenesis inhibitors may provide a new approach to the treatment of metastatic breast cancer. Bevacizumab is a monoclonal antibody against pathologic angiogenesis. A pivotal study (ECOG 2100) showed that bevacizumab in combination with paclitaxel increased progression-free survival for patients with metastatic breast cancer by 6 months. Subsequently, several clinical trials have shown that the combination of bevacizumab with a taxane can improve disease-free survival but does not prolong overall survival. While generally well tolerated, bevacizumab is potentially toxic for some patients who develop hypertension, proteinuria, bleeding, impaired wound healing, bowel perforation or thromboembolic events. Here, we review the current evidence for the use of bevacizumab in breast cancer and ongoing studies that address the questions of how to optimize regimens and schedules for the use of anti-angiogenic agents and the identification of those patients who would benefit the most from treatment with regimens that include antiangiogenic therapy.

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