Risk Factors for Second Primary Breast Cancer Among DCIS Survivors

描述（由申请人提供）：该研究是我们目前资助的项目的竞争性更新，该项目旨在调查流行病学因素、临床和病理特征以及肿瘤标志物表达如何影响原发性浸润性乳腺癌幸存者患第二原发性浸润性对侧乳腺癌的风险。在这里，我们建议通过评估导管原位癌（DCIS）幸存者中与第二原发性乳腺癌风险相关的因素来扩大这项工作。在美国，DCIS的发病率从1980年到2001年增加了7.2倍，主要是由于广泛的乳腺癌筛查。DCIS病变对现有治疗非常敏感，5年疾病特异性生存率接近100%。然而，与普通人群中患第一次乳腺癌的女性相比，DCIS幸存者患第二次乳腺癌的风险高出3.4至8.6倍。近年来DCIS发病率的快速上升已经转化为一个庞大且不断增长的DCIS幸存者群体，他们特别容易发展为第二次乳腺癌。并非所有DCIS患者都会发展为第二次乳腺癌，因此对于低风险的DCIS患者，某些手术和辅助治疗组合构成了过度治疗，而对于高风险的患者，另一些则构成了治疗不足。然而，目前缺乏有意义的预后指标来指示DCIS幸存者发生第二乳腺癌的风险是高还是低。这些预后指标可以作为重要的指导，帮助这些患者及其临床医生选择最合适的治疗方案和随后的随访护理。我们建议调查DCIS的流行病学、临床和组织病理学特征如何影响DCIS幸存者发生第二原发性乳腺癌的风险。我们将招募515名确诊为DCIS并确诊为第二原发原位或浸润性乳腺癌的患者，以及由1030名仅诊断为DCIS的患者组成的对照组，以达到以下具体目的：1)乳腺癌的流行病学危险因素，包括生殖特征、人体测量、外源性激素的使用、乳房x线摄影密度和乳腺癌家族史，如何影响DCIS幸存者总体、对侧和同侧第二原发性乳腺癌的风险？2) DCIS的临床和组织病理学特征，包括治疗方法、肿瘤分级和组织学亚型如何影响DCIS幸存者整体、对侧和同侧第二原发性乳腺癌的风险？拟议的研究将为快速增长的DCIS幸存者提供重要信息，因为其结果可能有助于调节他们患第二原发性乳腺癌的风险，并告知他们关于DCIS治疗和随后的乳腺癌筛查的决策。

DESCRIPTION (provided by applicant): The proposed study is a competitive renewal of our currently funded project that is investigating how epidemiological factors, clinical and pathological characteristics, and tumor marker expression influence the risk of second primary invasive contralateral breast cancer among survivors of a first primary invasive breast cancer. Here we propose to expand this work by evaluating factors that are related to risk of second primary breast cancers among ductal carcinoma in situ (DCIS) survivors. Incidence rates of DCIS have increased 7.2- fold from 1980 to 2001 in the United States, largely as a result of widespread breast cancer screening. DCIS lesions are very responsive to available therapies, and five-year disease-specific survival rates are close to 100%. However, DCIS survivors have a 3.4 to 8.6-fold higher risk of developing a second breast cancer compared to the risk that women in the general population have of developing a first breast cancer. The recent rapid rise in DCIS incidence rates has translated into a large and growing population of DCIS survivors who are particularly susceptible to developing a second breast cancer. Not all DCIS patients will go on to develop a second breast cancer, so certain surgical and adjuvant therapy combinations for DCIS constitute over- treatment for those at low risk of a second breast cancer, while others constitute under-treatment for those at high risk. At present, however, there is a lack of meaningful prognosticators to indicate which DCIS survivors are at high or low risk of developing a second breast cancer. Such prognosticators could be important guides to help these patients and their clinicians choose the most appropriate course of therapy and subsequent follow-up care. We propose to investigate how epidemiological, clinical, and histopathological characteristics of DCIS impact the risk of second primary breast cancers among DCIS survivors. We will recruit 515 patients diagnosed with DCIS and a verified subsequent second primary in situ or invasive breast cancer, and a control group consisting of 1,030 patients diagnosed only with DCIS to address the following specific aims: 1) How do epidemiological risk factors for breast cancer, including reproductive characteristics, anthropometric measures, use of exogenous hormones, mammographic density, and family history of breast cancer, influence the risks of second primary breast cancer overall, contralateral second primary breast cancer, and ipsilateral second primary breast cancer among DCIS survivors?; and 2) How do the clinical and histopathological features of DCIS, including treatments, tumor grade, and histological subtype impact risks of second primary breast cancer overall, contralateral second primary breast cancer, and ipsilateral second primary breast cancer among DCIS survivors? The proposed study will provide important information to the rapidly growing population of DCIS survivors as its results may help modulate their risk of developing a second primary breast cancer and inform their decision-making regarding DCIS treatments and subsequent breast cancer screening. Public Health Relevance: In the United States about 20% of all breast cancers diagnosed are of a type called ductal carcinoma in situ (DCIS). DCIS patients have a very high survival rate but also have a high risk of developing a second breast cancer, and little is known about which DCIS survivors will and will not go on to develop second breast cancers. The primary goal of this study is to identify epidemiological, clinical, and histopathological characteristics that may be associated with risk of second breast cancers that can help DCIS survivors make decisions regarding their treatment and follow-up.