Molecular Profiles and Lifestyle Factors in Breast Cancer Prognosis

乳腺癌预后中的分子谱和生活方式因素

• 批准号: 7795198
• 负责人: BETTE J CAAN
• 金额: $ 76.56万
• 依托单位: KAISER FOUNDATION RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2014-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7795198
• 关键词: Address; African American; Age; Archives; Area; Behavior; Behavioral; Biological; Biological Assay; Body Size; Body Weight Changes; Breast Cancer Risk Factor; Breast Feeding; California; Cancer Patient; Cancer Prognosis; Cancer Survivor; Cancer Survivorship; Caring; Cessation of life; Characteristics; Classification; Clinical; Clinical Data; Cohort Studies; Cost Savings; Cytokeratin; Data; Death Certificates; Diagnosis; Diet; Dietary Practices; Disease; Disease-Free Survival; Eligibility Determination; Epidemiology; Epidermal Growth Factor Receptor; Ethnic Origin; Etiology; Fatty acid glycerol esters; Freezing; Funding; Gene Expression; Goals; Heterogeneity; Hormone Receptor; Hormones; Human; Knowledge; Laboratories; Life; Life Style; Malignant Neoplasms; Medical; Medical Records; Menopausal Status; Methods; Molecular; Molecular Classification of Tumors; Molecular Profiling; Obesity; Outcome; Paraffin Embedding; Participant; Pathway interactions; Patient Self-Report; Physical activity; Population Heterogeneity; Positioning Attribute; Prevalence; Prognostic Factor; Prospective Studies; Public Health; Questionnaires; Race; Recruitment Activity; Recurrence; Reporting; Request for Proposals; Research; Research Personnel; Resources; Risk Factors; Sampling; Selection for Treatments; Self-Administered; Specimen; Staging; Suggestion; Surrogate Markers; Technology; Time; Tissues; Tumor Tissue; Variant; Weight; Weight Gain; Woman; Work; base; breast cancer diagnosis; cancer care; cancer epidemiology; cell type; cohort; cost; energy balance; epidemiology study; follow-up; improved; infancy; innovation; lifestyle factors; malignant breast neoplasm; molecular marker; new technology; older women; outcome forecast; parity; population based; programs; public health relevance; therapy development; tumor

DESCRIPTION (provided by applicant): In recent years, new technologies have allowed us to better characterize the heterogeneity of breast cancer and to identify a number of biological subtypes based on their molecular profiles. Consequently, molecular classification of tumors is increasingly being used to guide treatment selection and new treatment development, in evaluating prognosis, and in studies of etiology. One molecular classification, the "intrinsic subtype", which distinguishes among breast cancers based on either their cell type of origin (luminal A/B or basal) or whether the tumor is HER2-positive, has been used to identify biologically and clinically distinct subtypes of breast cancer. The primary goal of this proposal is to examine the effects of intrinsic subtypes and their relationship to breast cancer risk factors and short and long-term prognosis in two ongoing cohort studies of breast cancer survivors (N=4177) being conducted within the Kaiser Permanente of Northern California (KPNC) Medical Care program. The first study, the Life After Cancer Epidemiology (LACE) cohort, a population-based cohort of 2,288 women diagnosed with Stage I>1 cm, II, or IIIa breast cancer, was established in 2000- 2002 to examine behavioral factors and breast cancer prognosis. These data will be combined with 1890 additional cases of similar stage from the Pathways cohort, a study of short term breast cancer survivors which began in January 2006. Given the inconsistency observed to date in findings between energy related factors and prognosis and the suggestion that effects may vary by tumor characteristics such as hormone receptor status, a secondary goal of this proposal is to examine whether specific behaviors related to energy balance may be related to prognosis among breast cancer patients in general or primarily among women with certain intrinsic subtypes Since most studies have only reported on effects of energy related factors on short term prognosis, another secondary goal of this proposal is to continue to follow women in the LACE cohort up until 15 year post-diagnosis and to examine the relationship of energy related lifestyle factors with long-term prognosis. Data on weight, weight change, physical activity and diet were collected at multiple time points post diagnosis. Women are followed annually for recurrence and death by self report and verified by medical record and death certificates. During the proposed new funding period, archived tumor blocks will be retrieved and, using immunohistochemical assays (IHC), breast cancers will be classified into intrinsic subtypes. This study will achieve tremendous cost savings by examining the proposed questions within two existing cohort of cancer survivors for whom post diagnosis data on behavior are already available and by retrieving tumor specimens within a cohort where close to 90% the women belong to the KPNC, an HMO, where tumor specimens are readily accessible. Our proposal addresses a range of issues that are emerging priority areas in cancer survivorship research which will have both clinical and public health impact. PUBLIC HEALTH RELEVANCE: A limited number of studies with relatively small samples or short-term follow-up have classified tumors into intrinsic subtypes and examined their association with clinical tumor characteristics or survival. An even smaller number have looked at breast cancer risk factors. The combined LACE and Pathways cohorts, as proposed in this study constitutes one of the largest resources on breast cancer survivors with already collected clinical data from medical charts and lifestyle and other factors from self- administered questionnaires. The addition of the proposed intrinsic subtype (IHC) molecular markers to this resource provides an innovative and cost-efficient method for classifying breast cancer subtypes (IHC assays can be done on archived tumor tissue) that will improve our understanding of variation in prognosis, and also allows for the unique combination of molecular and behavioral information to help better understand which women are most likely to benefit from changes in lifestyle after a breast cancer diagnosis, information of both clinical and public health significance. This population-based cohort is uniquely positioned to address several important gaps in our knowledge about cancer survivorship.

描述（由申请人提供）：近年来，新技术使我们能够更好地表征乳腺癌的异质性，并根据其分子谱鉴定许多生物亚型。因此，肿瘤的分子分类越来越多地用于指导治疗选择和新的治疗发展，评估预后和病因研究。一种分子分类，即“内在亚型”，该分类基于乳腺癌的细胞类型（腔内A/B或基础）区分乳腺癌，或者肿瘤是否是HER2阳性的，已用于识别生物学和临床上不同的乳腺癌亚型。该提案的主要目的是检查内在的亚型及其与乳腺癌危险因素的关系及其与乳腺癌幸存者正在进行的队列研究（n = 4177）的短期和长期预后的影响，在北加州北加州的Kaiser Permanente（KPNC）内部进行。第一项研究是2000年至2002年建立了一个基于人群的癌症同类癌症，这是一名基于人群的队列，由2,288名被诊断为I> 1 cm，ii或IIIa乳腺癌的妇女进行检查，以检查行为因素和乳腺癌预后。这些数据将与途径队列的1890例其他相似阶段相似，对乳腺癌幸存者的一项研究始于2006年1月。鉴于能量相关因素和预后之间发现的不一致，并且在肿瘤的特征中可能会与肿瘤受体状态相关的乳腺癌与乳腺癌相关的效果是否有所不同在具有某些内在亚型的女性中，主要是因为大多数研究仅报告了与能量相关因素对短期预后的影响，因此该提案的另一个次要目标是继续跟随妇女进入蕾丝队列直至诊断后15年，并检查与能量相关的生活方式因素与长期预后的关系。诊断后多个时间点收集体重，体重变化，身体活动和饮食的数据。每年通过自我报告跟随妇女复发和死亡，并通过病历和死亡证明进行验证。在拟议的新资助期间，将检索存档的肿瘤块，并使用免疫组织化学测定（IHC），将乳腺癌分类为内在的亚型。这项研究将通过在两个现有的癌症幸存者中检查提出的问题来节省大量的成本，并在诊断后的行为数据中获得了诊断数据，并通过在妇女属于KPNC的近90％的同类中检索肿瘤标本，该妇女属于KPNC，HMO，HMO，HMO，肿瘤标本，可以轻松访问肿瘤标本。我们的提案解决了一系列问题，这些问题是癌症生存研究中新兴的优先领域，这些领域将对临床和公共卫生产生影响。公共卫生相关性：相对较少的样本或短期随访的研究有限的研究将肿瘤分类为内在的亚型，并检查了其与临床肿瘤特征或生存的关联。较少的数量研究了乳腺癌的危险因素。如本研究所提出的那样，蕾丝和途径的组合构成了乳腺癌幸存者最大的资源之一，其已经从医疗图表和生活方式中收集了临床数据，以及来自自我管理问卷的其他因素。在该资源中添加提出的固有亚型（IHC）分子标志物为对乳腺癌亚型进行分类（IHC测定可以进行分类（IHC测定）提供了创新且具有成本效益的方法（在存档的肿瘤组织中可以进行），从而可以改善我们对预后变化的理解，并可以更好地了解乳腺癌的独特信息。临床和公共卫生的意义。这个基于人群的队列的独特位置可以解决我们有关癌症生存的知识中的几个重要差距。