乳腺癌患者心理社会因素与免疫功能的相关性

免疫系统在肿瘤进展中有重要作用,心理社会因素也会影响肿瘤的发生、发展。乳腺癌相关心理社会因素主要包括应激性生活事件、应对方式、情绪和个性特征以及社会支持。相关免疫应答效应因素包括T淋巴细胞及其亚群等特异性免疫,TNF-a、巨噬细胞、NK细胞等非特异性免疫应答效应因素。探讨乳腺癌患者心理、肿瘤、免疫之间的关系,作为乳腺癌心理治疗的基础,具有重要意义。     

乳腺癌患者心理社会因素与免疫功能的相关性

免疫系统在肿瘤进展中有重要作用,心理社会因素也会影响肿瘤的发生、发展.乳腺癌相关心理社会因素主要包括应激性生活事件、应对方式、情绪和个性特征以及社会支持.相关免疫应答效应因素包括T淋巴细胞及其亚群等特异性免疫之间的关系,作为乳腺癌心理治疗的基础,具有重要意义.     

Neoadjuvant endocrine therapy for breast cancer: an overview

The clinical benefits of endocrine therapy for patients with hormonosensitive breast cancer remains perfectly established. For instance, tamoxifen, the gold standard of the adjuvant treatment, has largely contributed of the effectiveness of such a therapy. The recent development of new endocrine agents (the third-generation aromatase inhibitors, selective estrogen receptors modulators), provides to physicians the opportunity of a more effective and tolerable therapeutic approach, in the metastatic disease setting or likely in adjuvant setting for breast cancer patients. Preoperative therapy has been widely used for the treatment of initially inoperable locally advanced breast cancers with the main objective of breast-conserving surgery. The benefits of neoadjuvant chemotherapy has widely been demonstrated; however, the success of neoadjuvant endocrine therapy is much recent. The clinical and pharmacological data of the main published studies using neoadjuvant hormonotherapy are presented herein this review. Therefore, clinical and histologic assessments of response brings essential informations about the breast cancer hormonal sensitivity, but may also be predictor of the future (adjuvant or metastatic) treatment responsiveness.     

An overview of prognostic factors for long-term survivors of breast cancer

Background Numerous studies have examined prognostic factors for survival of breast cancer patients, but relatively few have dealt specifically with 10+-year survivors. Methods A review of the PubMed database from 1995 to 2006 was undertaken with the following inclusion criteria: median/mean follow-up time at least 10 years; overall survival and/or disease-specific survival known; and relative risk and statistical probability values reported. In addition, we used data from the long-standing Eindhoven Cancer Registry to illustrate survival probability as indicated by various prognostic factors. Results 10-year breast cancer survivors showed 90% 5-year relative survival. Tumor size, nodal status and grade remained the most important prognostic factors for long-term survival, although their role decreased over time. Most studies agreed on the long-term prognostic values of MI (mitotic index), LVI (lymphovascular invasion), Her2-positivity, gene profiling and comorbidity for either all or a subgroup of breast cancer patients (node-positive or negative). The roles of age, socioeconomic status, histological type, BRCA and p53 mutation were mixed, often decreasing after correction for stronger prognosticators, thus limiting their clinical value. Local and regional recurrence, metastases and second cancer may substantially impair long-term survival. Healthy lifestyle was consistently related to lower overall mortality. Conclusions Effects of traditional prognostic factors persist in the long term and more recent factors need further follow-up. The prognosis for breast cancer patients who have survived at least 10 years is favourable and increases over time. Improved long-term survival can be achieved by earlier detection, more effective modern therapy and healthier lifestyle.     

Herceptin and breast cancer: An overview for surgeons

IntroductionHER-2 over-expression is implicated in the pathogenesis of breast cancer and represents a key marker and determinant of patient outcome. Trastuzumab/Herceptin (TZ) is a recombinant humanised monoclonal antibody which targets HER-2. Introduction into clinical practice has significantly improved the natural history of HER-2 over-expressing tumors and has altered the standard of care for these women. This article reviews the established and emerging roles of TZ in the management of breast cancer (BC).MethodsLiterature review facilitated by Medline and PubMed databases.FindingsThe clinical utility of TZ was first established in the management of HER-2 over-expressing metastatic breast cancer (MBC), with improvements recognised in both the quality and quantity of life. Prospective randomized controlled trials have consistently demonstrated the efficacy of TZ for early breast cancer (EBC) in the adjuvant setting with significant improvements in disease free and overall survival. Emerging roles for TZ include neo-adjuvant therapy and the treatment of progressive disease. TZ is well tolerated and safe, however, associated cardiac dysfunction remains a significant clinical concern.ConclusionHER-2 status is critically important in the management algorithm for BC and should be determined in all cases. Quality assurance of laboratory testing is of paramount importance. TZ has an established role in the management of HER-2 positive MBC and EBC in conjunction with conventional chemotherapy. Appropriate patient selection and monitoring for cardiac dysfunction are required.     

免疫微环境促进肿瘤发生发展的机制研究进展

机体免疫有宿主保护和肿瘤促进双重作用免疫微环境对肿瘤的促进作用知之甚少。研究发现本文讨论免疫微环境可直接或间接地影响肿瘤的发生发展,其机制。其机制包括促进肿瘤血管生成、改变肿瘤的生物学特性、筛选适应微环境的肿瘤细胞存活或建立适宜的肿瘤微环境促进肿瘤进展,甚至可以调节肿瘤干细胞活性。基于免疫微环境在肿瘤发生发展中的重要作用,免疫治疗成为一种重要的抗肿瘤治疗手段,而探索免疫治疗和细胞毒药物或分子靶向药物联合的多模式治疗可能是未来肿瘤免疫治疗的方向。     

Inflammation and breast cancer. Balancing immune response: crosstalk between adaptive and innate immune cells during breast cancer progression

Recent insights into the molecular and cellular mechanisms underlying cancer development have revealed that immune cells functionally regulate epithelial cancer development and progression. Moreover, accumulated clinical and experimental data indicate that the outcome of an immune response toward an evolving breast neoplasm is largely determined by the type of immune response elicited. Acute tumor-directed immune responses involving cytolytic T lymphocytes appear to protect against tumor development, whereas immune responses involving chronic activation of humoral immunity, infiltration by Th2 cells, and protumor-polarized innate inflammatory cells result in the promotion of tumor development and disease progression. Herein we review this body of literature and summarize important new findings revealing the paradoxical role of innate and adaptive leukocytes as regulators of breast carcinogenesis.     

The effect of psychosocial factors on breast cancer outcome: a systematic review

Introduction

We sought to review the available evidence regarding the effect of psychosocial factors on the survival of breast cancer patients.

Methods

We systematically searched the PubMed and PsycINFO databases to identify relevant studies.

Results

We identified 31 studies examining the association of various psychosocial parameters with overall breast cancer survival/disease free survival and 6 studies examining whether psychological intervention influences the disease outcome. Of the 31 studies summarized in this overview, 25 (80.6%) showed a statistically significant association between at least one psychosocial variable and disease outcome. Parameters associated with better breast cancer prognosis are social support, marriage, and minimizing and denial, while depression and constraint of emotions are associated with decreased breast cancer survival; however, the role of these factors has not been verified in all studies.

Conclusion

Most of the studies show a significant relationship between psychosocial factors and survival, but the actual psychosocial variables related to survival are not consistently measured across studies and the findings for many of the psychosocial variables with survival/recurrence are not consistent across studies. Thus, more research is warranted regarding the role of social support, marriage, minimizing and denial, depression and constraint of emotions on breast cancer survival.     

Psychosocial factors in the development and progression of breast cancer

The factors responsible for the genesis of breast cancer remain unclear. Emerging, although controversial, evidence suggests that factors related to life-style, such as dietary fat or alcohol intake, or exposure to various forms of stressors, are associated with mammary tumorigenesis. The possible role of life-style factors in breast cancer is important in light of the fact that mortality to this disease is increasing in most countries and that development of curative therapies for breast cancer has not been forthcoming. Thus, determining the role of life-style factors in the onset and progression of breast cancer, particularly among individuals genetically vulnerable to breast cancer or women with breast cancer in remission, is critical to prevent this disease. We will review the three main hypotheses which have been suggested to link psychosocial factors to the etiology of cancer, emphasizing data obtained through animal models. Interpretation of the existing data suggests that the number of stressful life-events does not predict vulnerability to develop breast cancer or survival from it; a certain level of stress appears to protect from malignancies. The crucial factor affecting tumor growth is the interaction among stress, an individual's personality, and available psychosocial support, and the effect of this interaction on an individual's ability to cope with stress. In addition, other risk factors for breast cancer known to be closely associated with psychosocial factors, namely dietary fat and alcohol consumption, may interact with the effects of psychosocial factors on breast cancer.     

The impact of physical and psychosocial factors on work characteristics after cancer

Most previously employed cancer survivors continue to work after treatment, but the impact of cancer symptoms or psychosocial concerns on their work has seldom been assessed. We conducted a community-based survey of cancer survivors from the Colorado Central Cancer Registry to assess the changes in their work and the demographic, clinical, and psychosocial characteristics associated with work changes over the 2 years following diagnosis. Of 100 survivors, 92 returned to work, but 57% of those reduced their work by more than 4 h/week, and 56% noted a change in some aspect of their occupational role. Physical symptoms, particularly lack of energy or nausea/vomiting, and psychological symptoms, particularly feeling bored or useless or feeling depressed, were significantly associated with a reduction in work hours or a change in occupational role. Since changes in work are common and are associated with both physical and psychosocial symptoms, strategies are needed to reduce symptom burden and barriers to work and to improve work capacity for working-age cancer survivors.     

乳腺癌内分泌治疗耐药机制研究进展

内分泌治疗(ednocrine therapy,ET)是乳腺癌综合治疗中的重要措施之一,选择性雌激素受体调节剂(selectiveestrogen receptor modulators,SERMs)、第三代芳香化酶抑制剂(aromatase inhibi-tors,AIs)和氟维司群是重要的内分泌治疗药物。但目前内分泌疗法面临的最大难题是原、继发耐药,其确切机制尚不清楚,近年来的研究发现,多种因素与耐药相关,如ER信号传导途径中的共激活与共抑制因子的比例,HER-2生长因子受体的高表达,各生长因子和激酶的串话调节,雌激素受体基因关键氨基酸位点的突变和多态、芳香化酶基因的突变与多态以及他莫昔芬(tamoxifen,TAM)代谢异常等。     

Personality traits and psychosocial stress: quality of life over 2 years following breast cancer diagnosis and psychological impact factors

Objective: The aim of this study was to investigate changes in the quality of life (QoL) and body image among breast cancer patients over 2 years and to examine different predictive factors for QoL 2 years after the primary operation. Methods: A total of 203 women with a primary diagnosis of breast cancer completed the questionnaires 2 weeks and 6, 12, 18, and 24 months after surgery. Quality of Life Questionnaire (QLQ‐C30), Breast Cancer Specific Quality of Life Questionnaire Module (QLQ‐BR23), Questionnaire on Stress in Cancer Patients (QSC‐R23), Freiburg Personality Inventory (FPI‐R), Life Orientation Test (LOT) were used as standardized measures. Results: The overall QoL and most functional and symptom scales improved during the 2‐year period. However, cognitive functioning, body image, and the three symptom scales of insomnia, constipation, and diarrhea did not change. Age was only capable of predicting physical functioning, whereas tumor size, axillary surgery, and adjuvant chemotherapy were not predictive of the long‐term QoL functional scores. Initial distress was the most potent predictive factor for long‐term QoL. Baseline functioning predicted functional QoL scores 2 years later. And higher scores for neuroticism were associated with a poorer QoL. However, optimism was not capable of predicting the QoL 2 years later. Conclusion: Screening measures should be implemented at the time when breast cancer is diagnosed, in order to identify psychologically vulnerable patients and offer them professional psycho‐oncological help. Copyright © 2009 John Wiley & Sons, Ltd.     

Unraveling the mechanisms of endocrine resistance in breast cancer: new therapeutic opportunities.

Two thirds of breast cancers express the estrogen receptor (ER), which contributes to tumor development and progression. ER-targeted therapy is therefore widely used in breast cancer to inhibit signaling through ER and disrupt breast cancer growth. This therapeutic strategy, particularly using the antiestrogen tamoxifen, is proven to increase the cure rates in early breast cancer, improve patient outcomes in advanced disease, and reduce breast cancer incidence in the prevention setting. Despite the recent integration of more powerful endocrine agents into breast cancer care, resistance to all forms of endocrine therapy remains a major problem. New insight into ER biology and progress in understanding resistance mechanisms, mediated by molecular crosstalk between ER and various growth factor signaling pathways, are generating tremendous promise for new therapeutic opportunities to target resistance and improve breast cancer disease outcomes.     

Exercise in patients coping with breast cancer: An overview

Breast cancer is the most common type of cancer in women, but fortunately has high survival rates. Many studies have been performed to investigate the effects of exercise in patients diagnosed with breast cancer. There is evidence that exercise after the diagnosis of breast cancer improves mortality, morbidity, health related quality of life, fatigue, physical functioning, muscle strength, and emotional wellbeing. Based on scientific data, breast cancer patients should be recommended to participate in rehabilitation programs including aerobic and strength training. The aim of this article is to review the recently published data on the effect of exercise in patients with breast cancer in order to present the current perspective on the topic.     

Do psychosocial factors influence the course of breast cancer? A review of recent literature,methodological problems and future directions

The course of breast cancer is highly variable, and only part of the variability in progression rate can be predicted by clinicopathological factors. It is suggested that some of the variation may be ascribed to behavioral factors, but their importance in determining progression of breast cancer is still controversial. Several groups have found an association between progression of breast cancer and psychosocial factors including stressful life events, the expression of negative emotions—anger and anxiety—the presence of hopelessness, social support, and participating in psychosocial counselling. However, other groups failed to confirm these results. Here we review psycho-oncology research studies with breast cancer patients including those employing cross-sectional, longitudinal and experimental designs. Results of these studies, methodological problems and future directions for this line of research are discussed.     

The impact of psychosocial stress and stress management on immune responses in patients with cancer

The range of psychosocial stress factors/processes (eg, chronic stress, distress states, coping, social adversity) were reviewed as they relate to immune variables in cancer along with studies of psychosocial interventions on these stress processes and immune measures in cancer populations. The review includes molecular, cellular, and clinical research specifically examining the effects of stress processes and stress-management interventions on immune variables (eg, cellular immune function, inflammation), which may or may not be changing directly in response to the cancer or its treatment. Basic psychoneuroimmunologic research on stress processes (using animal or cellular/tumor models) provides leads for investigating biobehavioral processes that may underlie the associations reported to date. The development of theoretically driven and empirically supported stress-management interventions may provide important adjuncts to clinical cancer care going forward.     

Behaviour of breast cancer molecular subtypes through tumour progression

Introduction

Breast cancer (BC) becomes more aggressive throughout disease progression. Clinical stage is correlated with patient outcome. We hypothesised that BC molecular subtypes are associated with a poor prognosis in advanced clinical stages. We analysed the distribution and behaviour of molecular subtypes at different BC tumour size and variation of molecular subtype in recurrent lesions.

Patients and methods

We studied 1647 consecutive patients with non-metastatic invasive and microinvasive (Tmi) BC treated from January 1997 to December 2007. Patients were categorised by tumour size and molecular subtype. A chi-square method was used for multiple group comparisons. Kaplan-Meier product limit method was used to calculate overall survival and disease-free survival.

Results

Median follow-up was 7.2 years. For patients with invasive BC the median age was 56 years. Four hundred and fifteen patients recurred and 225 died. Larger tumours were more frequently of triple-negative (TN) subtype than small ones or Tmi lesions. Any molecular subtype change from primary tumour to recurrent lesions is more likely to happen from a good prognosis to a subtype of worse prognosis than the opposite. Larger tumours of luminal A, luminal B and TN, but not HER2 subtype, are more likely to carry aggressive markers and to have worse outcomes than small ones.

Conclusion

We found accumulation of TN subtype, migration to a poor prognosis subtype and increasing aggressiveness of luminal and TN subtypes throughout tumour progression. Tumours belonging to the HER2 subtype behave aggressively regardless of the primary size.     

乳腺癌内分泌治疗耐药机制的研究进展

乳腺癌是中国女性常见的恶性肿瘤之一,严重威胁着人们的健康和生命。70%~80%乳腺癌为激素受体阳性,目前针对这一类型乳腺癌的主要治疗手段为内分泌治疗。近几十年来内分泌治疗领域的新药不断问世并逐渐应用于临床,虽然对提高患者的疗效和延长生存时间方面带来希望,但内分泌治疗的耐药现状也受到人们重视。本文将对乳腺癌内分泌治疗的耐药机制和最新的研究结果进行综述,以期为乳腺癌内分泌治疗耐药的早期监测和干预提供新的思路。