UCI WOMEN'S BIOBEHAVIORAL PROCESSES AND HEALTH STUDY

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。乳腺癌目前是美国妇女的一个主要健康问题（美国癌症协会，1995年；Feuer等人，1993年）。BC的既定危险因素（如年龄、基因突变、家族和生殖史）在疾病发病率和进展的变异中只占有限的比例（Fox等，1994）；此外，这些风险因素中的大多数目前是不可改变的。对其他风险因素的研究促使临床医生和行为科学家解决了一个长期存在的关键问题：心理社会过程与乳腺癌之间的关系是什么？这一努力产生了一系列看似矛盾的发现。然而，已经确定了两类可能对BC发病率和进展有重要意义的预后变量——压力和心理应对方式。心理社会肿瘤学研究的主要弱点是：(1)依赖自我报告测量（问卷）来评估心理困扰和应对方式（Schwartz, 1995）；(2)对这些心理因素的生物学基础了解不足。本研究项目的主要目标是研究可能介导心理状态与癌症之间联系的假定的生物学过程。具体而言，本研究旨在进行横断面调查，以研究从大学乳腺癌综合护理中心（UCI Chao Family comprehensive cancer center）招募的早期乳腺癌女性（n=75）和健康匹配对照（n=75）的应激反应生物学指标与心理应对方式之间的关系。本研究的一个中心特征是建议使用基于实验室的行为挑战范式。行为挑战是心理挑战的标准操作化，它唤起了个体经历心理社会压力时所涉及的相同生理系统的反应。因此，受试者在经受这种轻微挑战时的反应代表了他们对社会心理压力的反应，然而，在受控环境中，这种挑战是短暂的，受试者的心理和生物反应是最小的。行为挑战程序包括暴露于温和的、标准化的行为挑战和在挑战应用之前、期间和之后对生物参数进行多次纵向测量。这种方法在当前背景下的重要性在于，它通过促进(1)更直接地评估个体的压力反应和应对研究，通过评估和自我报告相对公正地进行研究，以及(2)评估生物系统的反应性（例如，自主神经系统，神经系统，神经系统和神经系统），解决了上述文献中的弱点。神经内分泌系统)与挑战相关，并可能直接或间接与乳腺癌风险/进展相关。在本研究中，挑战的生物反应性将通过量化心率、血压、血浆ACTH和皮质醇水平对行为挑战的反应来衡量，而心理应对方式将通过量化挑战方案中唤醒的生物和自我报告指数之间的差异来衡量。要验证的主要研究假设是，患有乳腺癌的女性会表现出明显比健康对照组更大的生物应激反应。次要假设是BC家族史阳性的女性比家族史阴性的女性表现出更大的生物应激反应，绝经后的女性比绝经前的女性表现出更大的应激反应。该研究的具体目的是：具体目的1：量化患有和不患有乳腺癌的妇女对行为挑战范式的生物反应性参数。具体目标2：检查(a)患有和未患乳腺癌的女性在生物应激反应中的组间差异，以及(b)更年期和家族风险对生物应激反应和情绪表达的影响。具体目标3：开发方法并获得初步数据，以证明随后对高危人群进行前瞻性研究的合理性。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Breast cancer (BC) is presently a major health issue for women in the United States (American Cancer Society, 1995; Feuer et al 1993). Established risk factors for BC (e.g., age, gene mutations, familial and reproductive history) account for only a limited proportion of variance in disease incidence and progression (Fox et al, 1994); moreover, most of these risk factors are immutable at the present time. The search for additional risk factors has prompted clinicians and behavioral scientists to address a long-standing and critical question: what is the relationship between psychosocial processes and breast cancer? This effort has generated a literature of seemingly contradictory findings. However, two major classes of prognostic variables of probable significance for BC incidence as well as progression have been identified -- stress and psychological coping style. The major weakness of this body of psychosocial oncology research are: (1) the dependence on self-report measures (questionnaires) to assess psychological distress and coping style (Schwartz, 1995) and (2) a poor understanding of the biological substrates of these psychological factors. The broad objective of the present program of research is to study putative biological processes that may mediate the links between psychological states and cancer. Specifically, the present study is designed to conduct a cross-sectional investigation to examine associations between biological indices of stress reactivity and psychological coping styles in women with early stage breast cancer (n=75) and healthy, matched controls (n=75) recruited from a University-based comprehensive breast cancer care center (UCI Chao Family Comprehensive Cancer Center). A central feature of this study is the proposed use of a laboratory-based behavioral challenge paradigm. The behavioral challenge is a standard operationalization of psychological challenge that evokes responses from the same physiologic systems that are involved when an individual experiences psychosocial stress. The responses of subjects undergoing this mild challenge are thus representative of their responses to psychosocial stress, yet the challenge, given in a controlled setting, is brief and the psychological and biological responses evoked in subjects is minimal. The behavioral challenge procedure involves exposure to a mild, standardized behavioral challenge and multiple, longitudinal measurements of biological parameters before, during, and after the challenge application. The significance of this methodology in the present context is that it addresses the weaknesses in the literature described above by facilitating (1) more direct assessment of an individual's stress response and coping study that is relatively unbiased by appraisal and self-report and (2) the assessment of reactivity of biological systems (e.g., autonomic nervous, neuroendocrine systems) that are related to the challenge and may be related directly or indirectly to breast cancer risk/progression. In the present study, biological reactivity to challenge will be measured by quantifying changes in heart rate, blood pressure, and plasma levels of ACTH and cortisol in response to the behavioral challenge, whereas psychological coping styles will be measured by quantifying discrepancies between biological and self-report indices of arousal in response to challenge protocol. The major study hypothesis to be tested is that women with breast cancer will exhibit significantly greater biological stress reactivity than healthy controls. Secondary hypotheses are that women with a positive family history of BC will exhibit greater biological stress reactivity than women with a negative family history, and postmenopausal women will exhibit greater stress reactivity than premenopausal women. The specific aims of thie study are: Specific Aim 1: To quantify parameters of biological reactivity to a behavioral challenge paradigm in women with and without breast cancer. Specific Aim 2: To examine (a) group differences between women with and without breast cancer in biological stress reactivity, and (b) the effects of menopause and familial risk on biological stress reactivity and emotional expression. Specific Aim 3: To develop the methodology and obtain preliminary data which could justify subsequent, prospective research with high-risk populations.